Pancreatic Cancer Treatment (PDQ®)


Information for: Patients | Healthcare Professionals

General Information About Pancreatic Cancer

Pancreatic cancer is a disease in which malignant (cancer) cells form in the tissues of the pancreas.

The pancreas is a gland about 6 inches long that is shaped like a thin pear lying on its side. The wider end of the pancreas is called the head, the middle section is called the body, and the narrow end is called the tail. The pancreas lies between the stomach and the spine.

Anatomy of the pancreas; drawing shows the pancreas, stomach, spleen, liver, gallbladder, bile ducts, colon, and small intestine. An inset shows the head, body, and tail of the pancreas. The bile duct and pancreatic duct are also shown.
Anatomy of the pancreas. The pancreas has three areas: head, body, and tail. It is found in the abdomen near the stomach, intestines, and other organs.

The pancreas has two main jobs in the body:

  • To make juices that help digest (break down) food.
  • To make hormones, such as insulin and glucagon, that help control blood sugar levels. Both of these hormones help the body use and store the energy it gets from food.

The digestive juices are made by exocrine pancreas cells and the hormones are made by endocrine pancreas cells. About 95% of pancreatic cancers begin in exocrine cells.

This summary is about exocrine pancreatic cancer. For information on endocrine pancreatic cancer, see the PDQ summary on Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment.

For information on pancreatic cancer in children, see the PDQ summary on Unusual Cancers of Childhood.

Smoking and health history can affect the risk of pancreatic cancer.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. Talk with your doctor if you think you may be at risk.

Risk factors for pancreatic cancer include the following:

  • Smoking.
  • Being very overweight.
  • Having a personal history of diabetes or chronicpancreatitis.
  • Having a family history of pancreatic cancer or pancreatitis.
  • Having certain hereditaryconditions, such as:
    • Multiple endocrine neoplasia type 1 (MEN1) syndrome.
    • Hereditary nonpolyposis colon cancer (HNPCC; Lynch syndrome).
    • von Hippel-Lindau syndrome.
    • Peutz-Jeghers syndrome.
    • Hereditary breast and ovarian cancer syndrome.
    • Familial atypical multiple mole melanoma (FAMMM) syndrome.

Possible signs of pancreatic cancer include jaundice, pain, and weight loss.

These and other symptoms may be caused by pancreatic cancer. In the early stages of pancreatic cancer, there may not be any symptoms, or other conditions may cause the same symptoms.

Check with your doctor if you have any of the following problems:

  • Jaundice (yellowing of the skin and whites of the eyes).
  • Light-colored stools.
  • Dark urine.
  • Pain in the upper or middle abdomen and back.
  • Weight loss for no known reason.
  • Loss of appetite.
  • Feeling very tired.

Pancreatic cancer is difficult to detect (find) and diagnose early.

Pancreatic cancer is difficult to detect and diagnose for the following reasons:

  • There aren’t any noticeable signs or symptoms in the early stages of pancreatic cancer.
  • The signs of pancreatic cancer, when present, are like the signs of many other illnesses.
  • The pancreas is hidden behind other organs such as the stomach, small intestine, liver, gallbladder, spleen, and bile ducts.

Tests that examine the pancreas are used to detect (find), diagnose, and stage pancreatic cancer.

Pancreatic cancer is usually diagnosed with tests and procedures that make pictures of the pancreas and the area around it. The process used to find out if cancercells have spread within and around the pancreas is called staging. Tests and procedures to detect, diagnose, and stage pancreatic cancer are usually done at the same time. In order to plan treatment, it is important to know the stage of the disease and whether or not the pancreatic cancer can be removed by surgery.

The following tests and procedures may be used:

  • Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
  • Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances, such as bilirubin, released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it.
  • Tumor marker test: A procedure in which a sample of blood, urine, or tissue is checked to measure the amounts of certain substances, such as CA 19-9, and carcinoembryonic antigen (CEA), made by organs, tissues, or tumor cells in the body. Certain substances are linked to specific types of cancer when found in increased levels in the body. These are called tumor markers.
  • MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. A spiral or helical CTscan makes a series of very detailed pictures of areas inside the body using an x-ray machine that scans the body in a spiral path.
  • PET scan (positron emission tomography scan): A procedure to find malignanttumor cells in the body. A small amount of radionuclideglucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do. A PET scan and CT scan may be done at the same time. This is called a PET-CT.
  • Abdominal ultrasound: An ultrasound exam used to make pictures of the inside of the abdomen. The ultrasound transducer is pressed against the skin of the abdomen and directs high-energy sound waves (ultrasound) into the abdomen. The sound waves bounce off the internal tissues and organs and make echoes. The transducer receives the echoes and sends them to a computer, which uses the echoes to make pictures called sonograms. The picture can be printed to be looked at later.
  • Endoscopic ultrasound (EUS): A procedure in which an endoscope is inserted into the body, usually through the mouth or rectum. An endoscope is a thin, tube-like instrument with a light and a lens for viewing. A probe at the end of the endoscope is used to bounce high-energy sound waves (ultrasound) off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. This procedure is also called endosonography.
  • Endoscopic retrograde cholangiopancreatography (ERCP): A procedure used to x-ray the ducts (tubes) that carry bile from the liver to the gallbladder and from the gallbladder to the small intestine. Sometimes pancreatic cancer causes these ducts to narrow and block or slow the flow of bile, causing jaundice. An endoscope (a thin, lighted tube) is passed through the mouth, esophagus, and stomach into the first part of the small intestine. A catheter (a smaller tube) is then inserted through the endoscope into the pancreatic ducts. A dye is injected through the catheter into the ducts and an x-ray is taken. If the ducts are blocked by a tumor, a fine tube may be inserted into the duct to unblock it. This tube (or stent) may be left in place to keep the duct open. Tissue samples may also be taken.
  • Percutaneous transhepatic cholangiography (PTC): A procedure used to x-ray the liver and bile ducts. A thin needle is inserted through the skin below the ribs and into the liver. Dye is injected into the liver or bile ducts and an x-ray is taken. If a blockage is found, a thin, flexible tube called a stent is sometimes left in the liver to drain bile into the small intestine or a collection bag outside the body. This test is done only if ERCP cannot be done.
  • Laparoscopy: A surgical procedure to look at the organs inside the abdomen to check for signs of disease. Small incisions (cuts) are made in the wall of the abdomen and a laparoscope (a thin, lighted tube) is inserted into one of the incisions. The laparoscope may have an ultrasound probe at the end in order to bounce high-energy sound waves off internal organs, such as the pancreas. This is called laparoscopic ultrasound. Other instruments may be inserted through the same or other incisions to perform procedures such as taking tissue samples from the pancreas or a sample of fluid from the abdomen to check for cancer.
  • Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer. There are several ways to do a biopsy for pancreatic cancer. A fine needle or a core needle may be inserted into the pancreas during an x-ray or ultrasound to remove cells. Tissue may also be removed during a laparoscopy.

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options depend on the following:

  • Whether or not the tumor can be removed by surgery.
  • The stage of the cancer (the size of the tumor and whether the cancer has spread outside the pancreas to nearby tissues or lymph nodes or to other places in the body).
  • The patient’s general health.
  • Whether the cancer has just been diagnosed or has recurred (come back).

Pancreatic cancer can be controlled only if it is found before it has spread, when it can be completely removed by surgery. If the cancer has spread, palliative treatment can improve the patient's quality of life by controlling the symptoms and complications of this disease.

Stages of Pancreatic Cancer

Tests and procedures to stage pancreatic cancer are usually done at the same time as diagnosis.

The process used to find out if cancer has spread within the pancreas or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage of the disease in order to plan treatment. The results of some of the tests used to diagnosepancreatic cancer are often also used to stage the disease. See the General Information section for more information.

There are three ways that cancer spreads in the body.

Cancer can spread through tissue, the lymph system, and the blood:

  • Tissue. The cancer spreads from where it began by growing into nearby areas.
  • Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
  • Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

Cancer may spread from where it began to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.

  • Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.
  • Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if pancreatic cancer spreads to the liver, the cancer cells in the liver are actually pancreatic cancer cells. The disease is metastatic pancreatic cancer, not liver cancer.

The following stages are used for pancreatic cancer:

Stage 0 (Carcinoma in Situ)

In stage 0, abnormalcells are found in the lining of the pancreas. These abnormal cells may become cancer and spread into nearby normal tissue. Stage 0 is also called carcinoma in situ.

Tumor size compared to everyday objects; shows various measurements of a tumor compared to a pea, peanut, walnut, and lime
Pea, peanut, walnut, and lime show tumor sizes.

Stage I

Stage I pancreatic cancer; drawing on the left shows that stage IA pancreatic cancer is smaller than 2 centimeters. The drawing on the right shows that stage IB pancreatic cancer is larger than 2 centimeters. An inset shows that a 2 centimeter tumor is about the size of a peanut. The duodenum is also shown.
Stage I pancreatic cancer. In stage IA, the tumor is 2 centimeters or smaller. In stage IB, the tumor is larger than 2 centimeters.

In stage I, cancer has formed and is found in the pancreas only. Stage I is divided into stage IA and stage IB, based on the size of the tumor.

  • Stage IA: The tumor is 2 centimeters or smaller.
  • Stage IB: The tumor is larger than 2 centimeters.

Stage II

In stage II, cancer may have spread to nearby tissue and organs, and may have spread to lymph nodes near the pancreas. Stage II is divided into stage IIA and stage IIB, based on where the cancer has spread.

  • Stage IIA: Cancer has spread to nearby tissue and organs but has not spread to nearby lymph nodes.
    Stage IIA pancreatic cancer; drawing shows cancer in the pancreas and duodenum. The bile duct and pancreatic duct are also shown.
    Stage IIA pancreatic cancer. Cancer has spread to nearby tissue and organs but has not spread to nearby lymph nodes.
  • Stage IIB: Cancer has spread to nearby lymph nodes and may have spread to nearby tissue and organs.
    Stage IIB pancreatic cancer; drawing shows cancer in the pancreas and in nearby lymph nodes. Also shown are the bile duct, pancreatic duct, and duodenum.
    Stage IIB pancreatic cancer. Cancer has spread to nearby lymph nodes and may have spread to nearby tissue and organs.

Stage III

Stage III pancreatic cancer; drawing shows cancer in the pancreas, common hepatic artery, and portal vein. Also shown are the celiac axis (trunk), bile duct, pancreatic duct, duodenum, and superior mesenteric artery.
Stage III pancreatic cancer. Cancer has spread to the major blood vessels near the pancreas. These include the superior mesenteric artery, celiac axis, common hepatic artery, and portal vein. Cancer may have spread to nearby lymph nodes.

In stage III, cancer has spread to the major blood vessels near the pancreas and may have spread to nearby lymph nodes.

Stage IV

Stage IV pancreatic cancer; drawing shows cancer has spread beyond the pancreas. Inset shows cancer spreading through the blood and lymph nodes to the lung, liver, peritoneal cavity, and other parts of the body.
Stage IV pancreatic cancer. Cancer may be any size and has spread to distant organs, such as the lung, liver, and peritoneal cavity (the space in the abdomen that contains the intestines, stomach, and liver). Cancer may also have spread to tissue and organs near the pancreas or to lymph nodes.

In stage IV, cancer may be of any size and has spread to distant organs, such as the liver, lung, and peritoneal cavity. It may have also spread to organs and tissues near the pancreas or to lymph nodes.

Recurrent Pancreatic Cancer

Recurrentpancreatic cancer is cancer that has recurred (come back) after it has been treated. The cancer may come back in the pancreas or in other parts of the body.

Treatment Option Overview

There are different types of treatment for patients with pancreatic cancer.

Different types of treatment are available for patients with pancreatic cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Five types of standard treatment are used:

Surgery

One of the following types of surgery may be used to take out the tumor:

  • Whipple procedure: A surgical procedure in which the head of the pancreas, the gallbladder, part of the stomach, part of the small intestine, and the bile duct are removed. Enough of the pancreas is left to produce digestivejuices and insulin.
  • Total pancreatectomy: This operation removes the whole pancreas, part of the stomach, part of the small intestine, the common bile duct, the gallbladder, the spleen, and nearby lymph nodes.
  • Distal pancreatectomy: The body and the tail of the pancreas and usually the spleen are removed.

If the cancer has spread and cannot be removed, the following types of palliative surgery may be done to relieve symptoms and improve quality of life:

  • Surgical biliarybypass: If cancer is blocking the small intestine and bile is building up in the gallbladder, a biliary bypass may be done. During this operation, the doctor will cut the gallbladder or bile duct and sew it to the small intestine to create a new pathway around the blocked area.
  • Endoscopicstent placement: If the tumor is blocking the bile duct, surgery may be done to put in a stent (a thin tube) to drain bile that has built up in the area. The doctor may place the stent through a catheter that drains to the outside of the body or the stent may go around the blocked area and drain the bile into the small intestine.
  • Gastric bypass: If the tumor is blocking the flow of food from the stomach, the stomach may be sewn directly to the small intestine so the patient can continue to eat normally.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Combination chemotherapy is treatment using more than one anticancer drug. The way the chemotherapy is given depends on the type and stage of the cancer being treated.

See Drugs Approved for Pancreatic Cancer for more information.

Chemoradiation therapy

Chemoradiationtherapy combines chemotherapy and radiation therapy to increase the effects of both.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Tyrosine kinase inhibitors (TKIs) are targeted therapy drugs that block signals needed for tumors to grow. Erlotinib is a type of TKI used to treat pancreatic cancer.

There are treatments for pain caused by pancreatic cancer.

Pain can occur when the tumor presses on nerves or other organs near the pancreas. When pain medicine is not enough, there are treatments that act on nerves in the abdomen to relieve the pain. The doctor may inject medicine into the area around affected nerves or may cut the nerves to block the feeling of pain. Radiation therapy with or without chemotherapy can also help relieve pain by shrinking the tumor. See the PDQ summary on Pain for more information.

Patients with pancreatic cancer have special nutritional needs.

Surgery to remove the pancreas may affect its ability to make pancreatic enzymes that help to digest food. As a result, patients may have problems digesting food and absorbing nutrients into the body. To prevent malnutrition, the doctor may prescribe medicines that replace these enzymes. See the PDQ summary on Nutrition in Cancer Care for more information.

New types of treatment are being tested in clinical trials.

This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.

Biologic therapy

Biologic therapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Follow-up tests may be needed

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options by Stage

Stages I and II Pancreatic Cancer

Treatment of stage I and stage II pancreatic cancer may include the following:

  • Surgery.
  • Surgery followed by chemotherapy.
  • Surgery followed by chemoradiation.
  • A clinical trial of combination chemotherapy.
  • A clinical trial of chemotherapy and targeted therapy, with or without chemoradiation.
  • A clinical trial of chemotherapy and/or radiation therapy before surgery.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I pancreatic cancer and stage II pancreatic cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage III Pancreatic Cancer

Treatment of stage III pancreatic cancer may include the following:

  • Palliativesurgery or stent placement to bypass blocked areas in ducts or the small intestine.
  • Chemotherapy followed by chemoradiation.
  • Chemoradiation followed by chemotherapy.
  • Chemotherapy with or without targeted therapy.
  • A clinical trial of new anticancer therapies together with chemotherapy or chemoradiation.
  • A clinical trial of radiation therapy given during surgery or internal radiation therapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III pancreatic cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage IV Pancreatic Cancer

Treatment of stage IV pancreatic cancer may include the following:

  • Palliative treatments to relieve pain, such as nerve blocks, and other supportive care.
  • Palliative surgery or stent placement to bypass blocked areas in ducts or the small intestine.
  • Chemotherapy with or without targeted therapy.
  • Clinical trials of new anticancer agents with or without chemotherapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV pancreatic cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Treatment Options for Recurrent Pancreatic Cancer

Treatment of recurrentpancreatic cancer may include the following:

  • Palliativesurgery or stent placement to bypass blocked areas in ducts or the small intestine.
  • Palliative radiation therapy to shrink the tumor.
  • Other palliative medical care to reduce symptoms, such as nerve blocks to relieve pain.
  • Chemotherapy.
  • Clinical trials of chemotherapy, new anticancer therapies, or biologic therapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent pancreatic cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

To Learn More About Pancreatic Cancer

For more information from the National Cancer Institute about pancreatic cancer, see the following:

For general cancer information and other resources from the National Cancer Institute, see the following:


This information is provided by the National Cancer Institute.

This information was last updated on February 7, 2014.


General Information About Pancreatic Cancer

This summary provides information about the treatment of exocrine pancreatic cancer. Other PDQ summaries containing information related to cancer in the pancreas include the following:

  • Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment.
  • Unusual Cancers of Childhood Treatment (pancreatic cancer during childhood).

Incidence and Mortality

Estimated new cases and deaths from pancreatic cancer in the United States in 2014:[1]

  • New cases: 46,420.
  • Deaths: 39,590.

The incidence of carcinoma of the pancreas has markedly increased over the past several decades and ranks as the fourth leading cause of cancer death in the United States. Despite the high mortality rate associated with pancreatic cancer, its etiology is poorly understood.[2]

Risk Factors

Risk factors for development of pancreatic cancer include the following:[3][4]

  • A family history of pancreatic cancer.
  • Cigarette smoking.
  • Obesity.
  • Chronic pancreatitis.

Anatomy

 

Pancreas 
Anatomy of the pancreas.

 

Cancers of the pancreas are commonly identified by the site of involvement within the pancreas. Surgical approaches differ for masses in the head, body, tail, or uncinate process of the pancreas.

Clinical Features

Pancreatic cancer symptoms depend on the site of the tumor within the pancreas and the degree of tumor involvement.

In the early stages of pancreatic cancer there are not many noticeable symptoms. As the cancer grows, symptoms may include the following:

  • Jaundice.
  • Light-colored stools or dark urine.
  • Pain in the upper or middle abdomen and back.
  • Weight loss for no known reason.
  • Loss of appetite.
  • Fatigue.

Diagnostic and Staging Evaluation

Pancreatic cancer is difficult to detect and diagnose for the following reasons:

  • There are no noticeable signs or symptoms in the early stages of pancreatic cancer.
  • The signs of pancreatic cancer, when present, are like the signs of many other illnesses, such as pancreatitis or an ulcer.
  • The pancreas is obscured by other organs in the abdomen and is difficult to visualize clearly on imaging tests.

To appropriately treat pancreatic cancer, it is crucial to evaluate whether the cancer can be resected.

Imaging

The use of imaging technology may aid in the diagnosis of pancreatic cancer and in the identification of patients with disease that is not amenable to resection. Imaging tests that may be used include the following:[5]

  • Helical computed tomographic scan.
  • Magnetic resonance imaging scan.
  • Endoscopic ultrasound.
  • Minimally invasive techniques, such as laparoscopy and laparoscopic ultrasound may be used to decrease the use of laparotomy.[6][7]

Peritoneal cytology

In a case series of 228 patients, positive peritoneal cytology had a positive predictive value of 94%, specificity of 98%, and sensitivity of 25% for determining unresectability.[8]

Tumor markers

No tumor-specific markers exist for pancreatic cancer; markers such as serum cancer antigen (CA) 19-9 have low specificity. Most patients with pancreatic cancer will have an elevated CA 19-9 at diagnosis. Following or during definitive therapy, the increase of CA 19-9 levels may identify patients with progressive tumor growth.[9][Level of evidence: 3iDiii] The presence of a normal CA 19-9, however, does not preclude recurrence.

Prognosis and Survival

The primary factors that influence prognosis are:

  • Whether the tumor is localized and can be completely resected.
  • Whether the tumor has spread to lymph nodes or elsewhere.

Exocrine pancreatic cancer is rarely curable and has an overall survival (OS) rate of less than 6%.[10]

The highest cure rate occurs if the tumor is truly localized to the pancreas; however, this stage of disease accounts for less than 20% of cases. For patients with localized disease and small cancers (<2 cm) with no lymph node metastases and no extension beyond the capsule of the pancreas, complete surgical resection is associated with an actuarial 5-year survival rate of 18% to 24%.[11][Level of evidence: 3iA]

Surgical resection is the mainstay of curative treatment and provides a survival benefit in patients with small, localized pancreatic tumors. Patients with unresectable, metastatic, or recurrent disease are unlikely to benefit from surgical resection.

Pancreatic tumors are resistant to treatment with chemotherapy and radiation.

Patients with any stage of pancreatic cancer can appropriately be considered candidates for clinical trials because of the poor response to chemotherapy, radiation therapy, and surgery as conventionally used.

Palliative Therapy

Palliation of symptoms may be achieved with conventional treatment.

Palliative measures that may improve quality of life while not affecting OS include the following:[12][13]

  • Surgical or radiologic biliary decompression.
  • Relief of gastric outlet obstruction.
  • Pain control.
  • Psychological care to address the potentially disabling psychological events associated with the diagnosis and treatment of pancreatic cancer.[14]

(Refer to the Palliative Interventions section of the PDQ summary on Pain for more information.)

References:

  1. American Cancer Society.: Cancer Facts and Figures 2014. Atlanta, Ga: American Cancer Society, 2014. Available online. Last accessed February 14, 2014.

  2. Silverman DT, Schiffman M, Everhart J, et al.: Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer. Br J Cancer 80 (11): 1830-7, 1999.

  3. Tersmette AC, Petersen GM, Offerhaus GJ, et al.: Increased risk of incident pancreatic cancer among first-degree relatives of patients with familial pancreatic cancer. Clin Cancer Res 7 (3): 738-44, 2001.

  4. Nöthlings U, Wilkens LR, Murphy SP, et al.: Meat and fat intake as risk factors for pancreatic cancer: the multiethnic cohort study. J Natl Cancer Inst 97 (19): 1458-65, 2005.

  5. Riker A, Libutti SK, Bartlett DL: Advances in the early detection, diagnosis, and staging of pancreatic cancer. Surg Oncol 6 (3): 157-69, 1997.

  6. John TG, Greig JD, Carter DC, et al.: Carcinoma of the pancreatic head and periampullary region. Tumor staging with laparoscopy and laparoscopic ultrasonography. Ann Surg 221 (2): 156-64, 1995.

  7. Minnard EA, Conlon KC, Hoos A, et al.: Laparoscopic ultrasound enhances standard laparoscopy in the staging of pancreatic cancer. Ann Surg 228 (2): 182-7, 1998.

  8. Merchant NB, Conlon KC, Saigo P, et al.: Positive peritoneal cytology predicts unresectability of pancreatic adenocarcinoma. J Am Coll Surg 188 (4): 421-6, 1999.

  9. Willett CG, Daly WJ, Warshaw AL: CA 19-9 is an index of response to neoadjunctive chemoradiation therapy in pancreatic cancer. Am J Surg 172 (4): 350-2, 1996.

  10. Siegel R, Naishadham D, Jemal A: Cancer statistics, 2013. CA Cancer J Clin 63 (1): 11-30, 2013.

  11. Yeo CJ, Abrams RA, Grochow LB, et al.: Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg 225 (5): 621-33; discussion 633-6, 1997.

  12. Sohn TA, Lillemoe KD, Cameron JL, et al.: Surgical palliation of unresectable periampullary adenocarcinoma in the 1990s. J Am Coll Surg 188 (6): 658-66; discussion 666-9, 1999.

  13. Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001.

  14. Passik SD, Breitbart WS: Depression in patients with pancreatic carcinoma. Diagnostic and treatment issues. Cancer 78 (3 Suppl): 615-26, 1996.

Cellular Classification of Pancreatic Cancer

Pancreatic cancer includes the following carcinomas:

Malignant

  • Duct cell carcinoma (90% of all cases).
  • Acinar cell carcinoma.
  • Adenosquamous carcinoma.
  • Cystadenocarcinoma (serous and mucinous types).
  • Giant cell carcinoma.
  • Invasive adenocarcinoma associated with cystic mucinous neoplasm or intraductal papillary mucinous neoplasm.
  • Mixed type (ductal-endocrine or acinar-endocrine).
  • Mucinous carcinoma.
  • Pancreatoblastoma.
  • Papillary-cystic neoplasm (Frantz tumor). This tumor has lower malignant potential and may be cured with surgery alone.[1][2]
  • Papillary mucinous carcinoma.
  • Signet ring carcinoma.
  • Small cell carcinoma.
  • Unclassified.
  • Undifferentiated carcinoma.

Borderline Malignancies

  • Intraductal papillary mucinous tumor with dysplasia.[3]
  • Mucinous cystic tumor with dysplasia.
  • Pseudopapillary solid tumor.

References:

  1. Sanchez JA, Newman KD, Eichelberger MR, et al.: The papillary-cystic neoplasm of the pancreas. An increasingly recognized clinicopathologic entity. Arch Surg 125 (11): 1502-5, 1990.

  2. Warshaw AL, Compton CC, Lewandrowski K, et al.: Cystic tumors of the pancreas. New clinical, radiologic, and pathologic observations in 67 patients. Ann Surg 212 (4): 432-43; discussion 444-5, 1990.

  3. Sohn TA, Yeo CJ, Cameron JL, et al.: Intraductal papillary mucinous neoplasms of the pancreas: an increasingly recognized clinicopathologic entity. Ann Surg 234 (3): 313-21; discussion 321-2, 2001.

Stage Information for Pancreatic Cancer

The staging system for pancreatic exocrine cancer continues to evolve. The importance of staging beyond establishing whether a tumor is resectable is uncertain since state-of-the-art treatment has demonstrated little impact on survival. However, knowledge of the extent of the disease is necessary to communicate a uniform definition of disease.

AJCC Stage Groupings and TNM Definitions

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification.[1]

Table 1. Definitions of TNM Stage 0a

Stage

TNM

Description

0

Tis, N0, M0

Tis = Carcinoma in situ.b 

N0 = No regional lymph node metastasis.

M0 = No distant metastasis.

aReprinted with permission from AJCC: Exocrine and endocrine pancreas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 241-9.

bThis also includes the pancreatic intraepithelial neoplasia (PanIN)-3 classification.

Table 2. Definitions of TNM Stages IA and IB
Stage  TNM  Description 
IA T1, N0, M0 T1 = Tumor limited to the pancreas, ≤2 cm in greatest dimension.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
IB T2, N0, M0 T2 = Tumor limited to the pancreas, >2 cm in greatest dimension.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
aReprinted with permission from AJCC: Exocrine and endocrine pancreas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 241-9. 
Stage I pancreatic cancer; drawing on the left shows that stage IA pancreatic cancer is smaller than 2 centimeters. The drawing on the right shows that stage IB pancreatic cancer is larger than 2 centimeters. An inset shows that a 2 centimeter tumor is about the size of a peanut. The duodenum is also shown. 
Stage I pancreatic cancer; drawing on the left shows that stage IA pancreatic cancer is smaller than 2 centimeters. The drawing on the right shows that stage IB pancreatic cancer is larger than 2 centimeters. An inset shows that a 2 centimeter tumor is about the size of a peanut. The duodenum is also shown.
Table 3. Definitions of TNM Stage IIA
Stage  TNM  Description 
IIA T3, N0, M0 T3 = Tumor extends beyond the pancreas but without involvement of the celiac axis or the superior mesenteric artery.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
aReprinted with permission from AJCC: Exocrine and endocrine pancreas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 241-9. 
Stage IIA pancreatic cancer; drawing shows cancer in the pancreas and duodenum. The bile duct and pancreatic duct are also shown. 
Stage IIA pancreatic cancer; drawing shows cancer in the pancreas and duodenum. The bile duct and pancreatic duct are also shown.
Table 4. Definitions of TNM Stage IIBa
Stage  TNM  Description 
IIB T1, N1, M0 T1 = Tumor limited to the pancreas, ≤2 cm in greatest dimension.
N1 = Regional lymph node metastasis.
M0 = No distant metastasis.
T2, N1, M0 T2 = Tumor limited to the pancreas, >2 cm in greatest dimension.
N1 = Regional lymph node metastasis.
M0 = No distant metastasis.
T3, N1, M0 T3 = Tumor extends beyond the pancreas but without involvement of the celiac axis or the superior mesenteric artery.
N1 = Regional lymph node metastasis.
M0 = No distant metastasis.
aReprinted with permission from AJCC: Exocrine and endocrine pancreas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 241-9. 
Stage IIB pancreatic cancer; drawing shows cancer in the pancreas and in nearby lymph nodes. Also shown are the bile duct, pancreatic duct, and duodenum. 
Stage IIB pancreatic cancer; drawing shows cancer in the pancreas and in nearby lymph nodes. Also shown are the bile duct, pancreatic duct, and duodenum.
Table 5. Definitions of TNM Stage IIIa
Stage  TNM  Description 
III T4, Any N, M0 T4 = Tumor involves the celiac axis or the superior mesenteric artery (unresectable primary tumor).
NX = Regional lymph nodes cannot be assessed.
N0 = No regional lymph node metastasis.
N1 = Regional lymph node metastasis.
M0 = No distant metastasis.
aReprinted with permission from AJCC: Exocrine and endocrine pancreas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 241-9. 
Stage III pancreatic cancer; drawing shows cancer in the pancreas, common hepatic artery, and portal vein. Also shown are the celiac axis (trunk), bile duct, pancreatic duct, duodenum, and superior mesenteric artery. 
Stage III pancreatic cancer; drawing shows cancer in the pancreas, common hepatic artery, and portal vein. Also shown are the celiac axis (trunk), bile duct, pancreatic duct, duodenum, and superior mesenteric artery.
Table 6. Definitions of TNM Stage IVa
Stage  TNM  Description 
IV Any T, Any N, M1 TX = Primary tumor cannot be assessed.
T0 = No evidence of primary tumor.
Tis = Carcinoma in situ.b 
T1 = Tumor limited to the pancreas, ≤2 cm in greatest dimension.
T2 = Tumor limited to the pancreas, >2 cm in greatest dimension.
T3 = Tumor extends beyond the pancreas but without involvement of the celiac axis or the superior mesenteric artery.
T4 = Tumor involves the celiac axis or the superior mesenteric artery (unresectable primary tumor).
NX = Regional lymph nodes cannot be assessed.
N0 = No regional lymph node metastasis.
N1 = Regional lymph node metastasis.
M1 = Distant metastasis.
aReprinted with permission from AJCC: Exocrine and endocrine pancreas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 241-9. 
bThis also includes the pancreatic intraepithelial neoplasia (PanIN)-3 classification. 
Stage IV pancreatic cancer; drawing shows cancer has spread beyond the pancreas. Inset shows cancer spreading through the blood and lymph nodes to the lung, liver, peritoneal cavity, and other parts of the body. 
Stage IV pancreatic cancer; drawing shows cancer has spread beyond the pancreas. Inset shows cancer spreading through the blood and lymph nodes to the lung, liver, peritoneal cavity, and other parts of the body.

References:

  1. Exocrine and endocrine pancreas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 241-9.

Treatment Option Overview for Pancreatic Cancer

Surgical resection remains the primary modality when feasible; on occasion, resection can lead to long-term survival and provides effective palliation.[1][2][3][Level of evidence: 3iA]

The role of postoperative therapy (chemotherapy with or without chemoradiation therapy) in the management of pancreatic cancer remains controversial because much of the randomized clinical trial data available are statistically underpowered and provide conflicting results.[4][5][6][7][8]

Complications of pancreatic cancer include the following:

  • Malabsorption: Frequently, malabsorption caused by exocrine insufficiency contributes to malnutrition. Attention to pancreatic enzyme replacement can help alleviate this problem. (Refer to the PDQ summary on Nutrition in Cancer Care for more information.)
  • Pain: Celiac axis and intrapleural nerve blocks can provide highly effective and long-lasting control of pain for some patients. (Refer to the PDQ summary on Pain for more information.)

The survival rate of patients with any stage of pancreatic exocrine cancer is poor. Clinical trials are appropriate alternatives for treatment of patients with any stage of disease and should be considered before palliative approaches are selected.

Information about ongoing clinical trials for pancreatic cancer is available from the NCI Web site.

Table 7. Treatment Options for Pancreatic Cancer

Stage (TNM Staging Criteria)

Treatment Options

Stage I and stage II pancreatic cancer

Surgery

Postoperative chemoradiation therapy

Postoperative chemotherapy

Stage III pancreatic cancer

Palliative surgery

Chemoradiation therapy

Chemotherapy

Stage IV pancreatic cancer

Palliative therapy

Chemotherapy

Recurrent pancreatic cancer

Palliative therapy

Chemotherapy

References:

  1. Yeo CJ, Cameron JL, Lillemoe KD, et al.: Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg 221 (6): 721-31; discussion 731-3, 1995.

  2. Conlon KC, Klimstra DS, Brennan MF: Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg 223 (3): 273-9, 1996.

  3. Yeo CJ, Abrams RA, Grochow LB, et al.: Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg 225 (5): 621-33; discussion 633-6, 1997.

  4. Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Gastrointestinal Tumor Study Group. Cancer 59 (12): 2006-10, 1987.

  5. Kalser MH, Ellenberg SS: Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 120 (8): 899-903, 1985.

  6. Klinkenbijl JH, Jeekel J, Sahmoud T, et al.: Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg 230 (6): 776-82; discussion 782-4, 1999.

  7. Neoptolemos JP, Dunn JA, Stocken DD, et al.: Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet 358 (9293): 1576-85, 2001.

  8. Neoptolemos JP, Stocken DD, Friess H, et al.: A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350 (12): 1200-10, 2004.

Stage I and Stage II Pancreatic Cancer Treatment

Treatment Options for Stages I and II Pancreatic Cancer

Treatment options for stages I and II pancreatic cancer include the following:

  1. Surgery: radical pancreatic resection including:
    • Whipple procedure (pancreaticoduodenal resection).
    • Total pancreatectomy when necessary for adequate margins.
    • Distal pancreatectomy for tumors of the body and tail of the pancreas.[1][2]
     
  2. Postoperative chemoradiation therapy: radical pancreatic resection followed by 5-fluorouracil (5-FU) chemotherapy and radiation therapy.[3][4][5][6][7]
  3. Postoperative chemotherapy: radical pancreatic resection followed by chemotherapy (gemcitabine or 5-FU/leucovorin).[8]

Surgery

Complete resection can yield 5-year survival rates of 18% to 24%, but ultimate control remains poor because of the high incidence of both local and distant tumor recurrence.[9][10][11][Level of evidence: 3iA]

Approximately 20% of patients present with pancreatic cancer amenable to local surgical resection, with operative mortality rates of approximately 1% to 16%.[12][13][14][15][16] Using information from the Medicare claims database, a national cohort study of more than 7,000 patients undergoing pancreaticoduodenectomy between 1992 and 1995 revealed higher in-hospital mortality rates at low-volume hospitals (<1 pancreaticoduodenectomy per year) versus high-volume hospitals (>5 per year) (16% vs. 4%, respectively; P < .01).[12]

Postoperative chemoradiation therapy

The role of postoperative therapy (chemotherapy with or without chemoradiation therapy) in the management of this disease remains controversial because much of the randomized clinical trial data available are statistically underpowered and provide conflicting results.[3][4][5][6][7]

Evidence (postoperative chemoradiation therapy):

Several phase III trials examined the potential overall survival (OS) benefit of postoperative adjuvant 5-FU–based chemoradiation therapy:

  1. Gastrointestinal Study Group (GITSG): A small randomized trial conducted by the GITSG in 1985 compared surgery alone with surgery followed by chemoradiation.[3][Level of evidence: 1iiA];[4][Level of evidence: 2A]
    • The investigators reported a significant but modest improvement in median-term and long-term survival over resection alone with postoperative bolus 5-FU and regional split-course radiation given at a dose of 40 Gy.
     
  2. European Organization for the Research and Treatment of Cancer (EORTC): An attempt by the EORTC to reproduce the results of the GITSG trial failed to confirm a significant benefit for adjuvant chemoradiation therapy over resection alone;[5][Level of evidence: 1iiA] however, this trial treated patients with pancreatic and periampullary cancers (with a potentially better prognosis).
    • A subset analysis of the patients with primary pancreatic tumors indicated a trend toward improved median, 2-year, and 5-year OS with adjuvant therapy compared with surgery alone (17.1 months, 37%, and 20%, respectively, vs. 12.6 months, 23%, and 10%, respectively; P = .09 for median survival).
     
  3. An updated analysis of a subsequent European Study for Pancreatic Cancer (ESPAC 1) trial examined only patients who underwent strict randomization after pancreatic resection. The patients were assigned to one of four groups (observation, bolus 5-FU chemotherapy, bolus 5-FU chemoradiation therapy, or chemoradiation therapy followed by additional chemotherapy).[6][7][17][Level of evidence: 1iiA]
    • With a 2 × 2 factorial design reported at a median follow-up of 47 months, a median survival benefit was observed for only the patients who received postoperative 5-FU chemotherapy. However, these results were difficult to interpret because of a high rate of protocol nonadherence and the lack of a separate analysis for each of the four groups in the 2 × 2 design.
     
  4. U.S. Gastrointestinal Intergroup: The U.S. Gastrointestinal Intergroup has reported the results of a randomized phase III trial (Radiation Therapy Oncology Group (RTOG)-9704) that included 451 patients with resected pancreatic cancers who were assigned to receive either postoperative infusional 5-FU plus infusional 5-FU and concurrent radiation or adjuvant gemcitabine plus infusional 5-FU and concurrent radiation.[18][Level of evidence: 1iiA] The primary endpoints were OS for all patients and OS for patients with pancreatic head tumors.
  5. A 5-year update of RTOG-9704 reported that patients with pancreatic head tumors (n = 388) had a median survival and 5-year OS of 20.5 months and 22% survival rate with gemcitabine, versus 17.1 months and 18% with 5-FU (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.67–1.05; P = .12).[19]
    • Univariate analysis showed no difference in OS; however, on multivariate analysis, patients on the gemcitabine arm with pancreatic head tumors experienced a trend toward improved OS (P = .08). Distant relapse remained the predominant site of first failure (78%).
     
  6. A secondary analysis of RTOG-9704 explored the correlation of adherence to protocol-specified radiation with patient outcomes.
    • Radiation therapy adherence was scored as per protocol (n = 216) and less than per protocol (n = 200). The major deviation seen was deviation in field size and field placement.
    • For all pancreatic sites, median survival for patients per protocol was significantly longer than patients treated less than per protocol (1.74 years vs. 1.46 years; P = .008).
    • On multivariate analysis, treatment per protocol correlated more strongly with median survival than assigned treatment arm (P = .014). However, this is an exploratory analysis that cannot control for potential unknown confounders.
     

The EORTC/U.S. Gastrointestinal Intergroup RTOG-0848 phase III adjuvant trial evaluating the impact of chemoradiation after completion of a full course of gemcitabine with or without erlotinib is currently enrolling patients.

Postoperative chemotherapy

Evidence (postoperative chemotherapy):

  1. Charité Onkologie (CONKO)-001: Results have also been reported from CONKO-001, a multicenter phase III trial of 368 patients with resected pancreatic cancer who were randomly assigned to receive six cycles of adjuvant gemcitabine versus observation.[20][Level of evidence: 1iiDii] In contrast to the previous trials, the primary endpoint was disease-free survival (DFS).
    • Median DFS was 13.4 months in the gemcitabine arm (95% CI, 11.6–15.3) and 6.7 months in the observation arm (95% CI, 6.0–7.5; P < .001). In this initial publication of results, there was no significant difference in OS between the gemcitabine arm (median 22.1 months; 95% CI, 18.4–25.8) and the control arm (median 20.2 months; 95% CI, 17–23.4).
    • With a median follow-up of 136 months, long-term follow-up of the CONKO-001 study demonstrates a significant improvement in OS that favors gemcitabine (median survival 22.8 months vs. 20.2 months; HR, 0.76; 95% CI, 0.61–0.95, P = .01). Gemcitabine compared with observation alone yielded improved survival rates at 5 years of 20.7% for the gemcitabine arm versus 10.4% for the observation-alone arm and at 10 years the survival rates were 12.2% for the gemcitabine arm versus 7.7% for the observation-alone arm.[21][Level of evidence: 1iiA]
     
  2. ESPAC-3: The ESPAC-3 (NCT00058201) trial randomly assigned 1,088 patients who had undergone complete macroscopic resection to either 6 months of 5-FU (425 mg/m2) and leucovorin (20 mg/m2) on days 1 to 5 every 28 days or 6 months of gemcitabine (1,000 mg/m2) on days 1, 8, and 15 every 28 days.[8][Level of evidence: 1iiA]
    • Median OS was 23.0 months (95% CI, 21.1– 25.0) for patients treated with 5-FU plus leucovorin and 23.6 months (95% CI, 21.4–26.4) for those treated with gemcitabine (HR = 0.94; 95% CI, 0.81–1.08; P = .39).
     

Additional trials are still warranted to determine more effective adjuvant therapy for this disease.

Treatment Options Under Clinical Evaluation for Stages I and II Pancreatic Cancer

Treatment options under clinical evaluation include the following:

  1. Gemcitabine and capecitabine ( ESPAC-4).
  2. Gemcitabine and erlotinib ( CONKO-005).
  3. Gemcitabine and erlotinib with or without 5-FU/capecitabine-based chemoradiation (RTOG-0848).
  4. Preoperative chemotherapy and/or radiation therapy.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I pancreatic cancer and stage II pancreatic cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Dalton RR, Sarr MG, van Heerden JA, et al.: Carcinoma of the body and tail of the pancreas: is curative resection justified? Surgery 111 (5): 489-94, 1992.

  2. Brennan MF, Moccia RD, Klimstra D: Management of adenocarcinoma of the body and tail of the pancreas. Ann Surg 223 (5): 506-11; discussion 511-2, 1996.

  3. Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Gastrointestinal Tumor Study Group. Cancer 59 (12): 2006-10, 1987.

  4. Kalser MH, Ellenberg SS: Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 120 (8): 899-903, 1985.

  5. Klinkenbijl JH, Jeekel J, Sahmoud T, et al.: Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg 230 (6): 776-82; discussion 782-4, 1999.

  6. Neoptolemos JP, Dunn JA, Stocken DD, et al.: Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet 358 (9293): 1576-85, 2001.

  7. Neoptolemos JP, Stocken DD, Friess H, et al.: A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350 (12): 1200-10, 2004.

  8. Neoptolemos JP, Stocken DD, Bassi C, et al.: Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA 304 (10): 1073-81, 2010.

  9. Cameron JL, Crist DW, Sitzmann JV, et al.: Factors influencing survival after pancreaticoduodenectomy for pancreatic cancer. Am J Surg 161 (1): 120-4; discussion 124-5, 1991.

  10. Yeo CJ, Cameron JL, Lillemoe KD, et al.: Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg 221 (6): 721-31; discussion 731-3, 1995.

  11. Yeo CJ, Abrams RA, Grochow LB, et al.: Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg 225 (5): 621-33; discussion 633-6, 1997.

  12. Birkmeyer JD, Finlayson SR, Tosteson AN, et al.: Effect of hospital volume on in-hospital mortality with pancreaticoduodenectomy. Surgery 125 (3): 250-6, 1999.

  13. Cameron JL, Pitt HA, Yeo CJ, et al.: One hundred and forty-five consecutive pancreaticoduodenectomies without mortality. Ann Surg 217 (5): 430-5; discussion 435-8, 1993.

  14. Spanknebel K, Conlon KC: Advances in the surgical management of pancreatic cancer. Cancer J 7 (4): 312-23, 2001 Jul-Aug.

  15. Balcom JH 4th, Rattner DW, Warshaw AL, et al.: Ten-year experience with 733 pancreatic resections: changing indications, older patients, and decreasing length of hospitalization. Arch Surg 136 (4): 391-8, 2001.

  16. Sohn TA, Yeo CJ, Cameron JL, et al.: Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg 4 (6): 567-79, 2000 Nov-Dec.

  17. Choti MA: Adjuvant therapy for pancreatic cancer--the debate continues. N Engl J Med 350 (12): 1249-51, 2004.

  18. Regine WF, Winter KA, Abrams RA, et al.: Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA 299 (9): 1019-26, 2008.

  19. Regine WF, Winter KA, Abrams R, et al.: Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the U.S. Intergroup/RTOG 9704 phase III trial. Ann Surg Oncol 18 (5): 1319-26, 2011.

  20. Oettle H, Post S, Neuhaus P, et al.: Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 297 (3): 267-77, 2007.

  21. Oettle H, Neuhaus P, Hochhaus A, et al.: Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA 310 (14): 1473-81, 2013.

Stage III Pancreatic Cancer Treatment

Treatment Options for Stage III Pancreatic Cancer

While stage III and stage IV pancreatic cancer are both incurable, the natural history of stage III (locally advanced) disease may be different than it is for stage IV disease. An autopsy series demonstrated that 30% of patients presenting with stage III disease died without evidence of distant metastases.[1][Level of evidence: 1iiA] Therefore, investigators have struggled with the question of whether chemoradiation for patients presenting with stage III disease is warranted.

Treatment options for stage III pancreatic cancer include the following:

  1. Palliative surgery: palliative surgical biliary and/or gastric bypass, percutaneous radiologic biliary stent placement, or endoscopic biliary stent placement.[2][3]
  2. Chemoradiation therapy:
    • Chemoradiation followed by chemotherapy.
    • Chemotherapy followed by chemoradiation, for patients without metastatic disease.
     
  3. Chemotherapy: gemcitabine; gemcitabine and erlotinib; gemcitabine and nab-paclitaxel; or 5-fluorouracil (5-FU), leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX).

Palliative surgery

A significant proportion (approximately one-third) of patients with pancreatic cancer will present with stage III or locally advanced disease. Patients with stage III pancreatic cancer have tumors that are technically unresectable because of local vessel impingement or invasion by tumor. These patients may benefit from palliation of biliary obstruction by endoscopic, surgical, or radiological means.[4]

Chemoradiation therapy

The role of chemoradiation in locally advanced pancreatic cancer remains controversial. Table 8 summarizes phase III randomized studies of chemoradiation for stage III pancreatic cancer.

Table 8. Randomized Studies in Stage III Pancreatic Cancer: Median Survival

Trial

Regimen

Chemoradiation

Radiation Alone

Chemotherapy Alone

P Value

Pre-2000  

 

GITSG [5]

Radiation alone vs. 5-FU/60 Gy XRT

40 weeks

20 weeks

 

<.01

ECOG [6]

Radiation vs. 5-FU, mitomycin C/59 Gy XRT

8.4 months

7.1 months

 

.16

Post-2000  

 

FFCD [7]

GEM vs. GEM, cisplatin, 60 Gy XRT

8.6 months

 

13 months

.03

ECOG [8]

GEM vs. GEM/50.4 Gy XRT

11.1 months

 

9.2 months

.017

5-FU = 5-fluorouracil; ECOG = Eastern Cooperative Oncology Group; FFCD = Fédération Francophone de Cancérologie Digestive; GEM = gemcitabine; GITSG = Gastrointestinal Tumor Study Group; Gy = gray (unit of absorbed radiation of ionizing radiation); P value = probability value; XRT = x-ray or radiation therapy.

Evidence (chemoradiation therapy):

Three trials attempted to look at combined modality therapy versus radiation therapy alone.[5][6][7] The trials had substantial deficiencies in design or analysis. Initially, the standard of practice was to give chemoradiation therapy based on data from the first two studies; however, with the publication of the third study, standard practice has changed to chemotherapy followed by chemoradiation in the absence of metastases.

  1. Gastrointestinal Tumor Study Group (GITSG)-9273 trial: Prior to 2000, several phase III trials evaluated combined modality therapy versus radiation therapy alone. Before the use of gemcitabine for patients with locally advanced or metastatic pancreatic cancer, investigators from the GITSG randomly assigned 106 patients with locally advanced pancreatic adenocarcinoma to receive external-beam radiation therapy (EBRT) (60 Gy) alone or concurrent EBRT (either 40 Gy or 60 Gy) plus bolus 5-FU.[5][Level of evidence: 1iiA]
    • The study was stopped early when the chemoradiation therapy arms were found to have better efficacy. The 1-year survival was 11% for patients who received EBRT alone compared with 38% for patients who received chemoradiation therapy with 40 Gy and 36% for patients who received chemoradiation therapy with 60 Gy.
    • After an additional 88 patients were enrolled in the combined modality arms, there was a trend toward improved survival with 60 Gy EBRT plus 5-FU, but the difference in time-to-progression and overall survival (OS) was not statistically significant when compared with the 40 Gy arm.[9]
     
  2. Eastern Cooperative Oncology Group (ECOG) E-8282 trial: Investigators from the ECOG randomly assigned 114 patients to receive radiation therapy (59.4 Gy) alone or with concurrent infusional 5-FU (1,000 mg/m2 daily on days 2–5 and 28–31) plus mitomycin (10 mg/m2 on day 2). [6]
    • The trial reported no difference in OS between the two groups.
     
  3. Fédération Francophone de Cancérologie Digestive-Société Française de Radiothérapie Oncologie (FFCD-SFRO) trial: As it became clear that radiation therapy alone was an inadequate treatment, investigators evaluated combined modality approaches versus chemotherapy alone. Investigators from the FFCD-SFRO randomly assigned 119 patients to induction chemoradiation therapy (60 Gy in 2 Gy fractions with 300 mg/m2/day of continuous-infusion 5-FU on days 1–5 for 6 weeks and 20 mg/m2/day of cisplatin on days 1–5 during weeks 1 and 5) or induction gemcitabine (1,000 mg/m2 weekly for 7 weeks). Maintenance gemcitabine was administered to both groups until stopped by disease progression or treatment discontinuation as a result of toxicity. [10][Level of evidence: 1iiA]
    • Median survival was superior in the gemcitabine arm (13 vs. 8.6 months; P = .03).
    • Nonhematological grade 3 to 4 toxicities (primarily gastrointestinal) were significantly more common in the chemoradiation therapy arm (44% vs. 18%; P = .004), and fewer patients completed at least 75% of induction therapy (42% vs. 73%).
    • Nonetheless, the survival benefit persisted in a per-protocol analysis of patients receiving at least 75% of planned therapy. Notably, the dose intensity of maintenance gemcitabine was significantly less in the chemoradiation therapy arm because of a greater incidence of grades 3 to 4 hematological toxicities (71% vs. 27%; P = .0001).
    • As a result of this study, induction chemoradiation therapy has fallen out of favor.
     
  4. ECOG: The results of the FFCD-SFRO study stand in contrast to the results of a study from ECOG in which investigators randomly assigned 74 patients to either gemcitabine alone or gemcitabine with radiation followed by gemcitabine.[8] Of note, the study was closed early as the result of poor accrual.
    • The primary endpoint was survival, which was 9.2 months (95% confidence interval [CI], 7.9–11.4 months) and 11.1 months (95% CI, 7.6–15.5 months) for chemotherapy and combined modality therapy, respectively (one-sided P = .017 by stratified log-rank test).
    • Grades 4 and 5 toxicity were greater in the chemoradiation therapy arm than in the chemotherapy arm (41% vs. 9%).
     
  5. Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR): Given the increased toxicity of chemoradiation therapy and the early development of metastatic disease in a large percentage of patients with stage III pancreatic cancer, investigators are pursuing a strategy of selecting patients with localized disease for chemoradiation therapy. With this strategy, the selected patients have an absence of progressive disease locally or systemically after several months of chemotherapy.[11][Level of evidence: 3iiiA]
    • A retrospective analysis of 181 patients enrolled in prospective phase II and III GERCOR studies revealed that 29% had metastatic disease after 3 months of gemcitabine-based chemotherapy.
    • For the remaining 71%, median OS was significantly longer among patients treated with chemoradiation therapy than among patients treated with additional chemotherapy (15.0 months vs. 11.7 months; P = .0009).
     

Taken together, the FFCD and GERCOR studies provide support for gemcitabine-based chemotherapy for at least 3 months, followed by chemoradiation in the absence of metastatic disease. This approach has yet to be validated in a prospective phase III trial.

Chemotherapy

Chemotherapy is the primary treatment modality for patients with locally advanced pancreatic cancers. Although gemcitabine has long been considered the standard regimen, newer chemotherapy regimens have recently emerged.

Evidence: (chemotherapy):

  1. Gemcitabine versus 5-FU: Gemcitabine has demonstrated activity in patients with pancreatic cancer and is a useful palliative agent.[12][13][14] A phase III trial of gemcitabine versus 5-FU as first-line therapy in patients with advanced or metastatic adenocarcinoma of the pancreas reported a significant improvement in survival among patients treated with gemcitabine (1-year survival was 18% with gemcitabine compared with 2% with 5-FU; P = .003).[13][Level of evidence: 1iiA]
  2. Gemcitabine alone versus gemcitabine and erlotinib: The National Cancer Institute of Canada performed a phase III trial (CAN-NCIC-PA3 [NCT00026338]) that compared gemcitabine alone versus the combination of gemcitabine and erlotinib (100 mg/day) in patients with advanced or metastatic pancreatic carcinomas.[15][Level of evidence: 1iiA]
    • The addition of erlotinib modestly prolonged survival when combined with gemcitabine versus gemcitabine alone (hazard ratio [HR] = 0.81; 95% CI, 0.69 to 0.99; P = .038).
    • The corresponding median and 1-year survival rates for patients who received erlotinib versus placebo were 6.2 months and 5.9 months, and 23% versus 17%, respectively.
     
  3. Platinum analog or fluoropyrimidine versus single-agent gemcitabine: Many phase III studies have evaluated a combination regimen with either a platinum analog (cisplatin or oxaliplatin) or fluoropyrimidine versus single-agent gemcitabine.[16][17]
    • Not one of these phase III trials has demonstrated a statistically significant advantage favoring the use of combination chemotherapy in the first-line treatment of metastatic pancreatic cancer.
     
  4. Gemcitabine and nab-paclitaxel versus gemcitabine: A multicenter, international phase III trial (NCT00844649) included 861 patients with metastatic pancreatic adenocarcinoma (Karnofsky Performance Status of ≥70) who had not previously received chemotherapy for metastatic disease.[18][Level of evidence: 1iiA] Patients who received adjuvant gemcitabine or any other chemotherapy were excluded. The patients were randomly assigned to receive gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2 of body-surface area) weekly for 3 of 4 weeks or gemcitabine monotherapy (1000 mg/m2 weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks).
    • The median OS was 8.5 months in the nab-paclitaxel/gemcitabine group compared with 6.7 months in the gemcitabine group (HRdeath, 0.72; 95% CI, 0.62–0.83; P < .001).
    • Median progression-free survival was 5.5 months in the nab-paclitaxel/gemcitabine group and 3.7 months in the gemcitabine group (HRdisease progression, 0.69; 95% CI, 0.58–0.82; P < .001).
    • Nab-paclitaxel/gemcitabine was more toxic than gemcitabine. The most common grade 3 toxicities were neutropenia (38% in the nab-paclitaxel/gemcitabine group vs. 27% in the gemcitabine group), fatigue (17% in the nab-paclitaxel/gemcitabine group vs. 1% in the gemcitabine group), and neuropathy (17% in the nab-paclitaxel/gemcitabine group vs. 1% in the gemcitabine group). Febrile neutropenia occurred in 3% of the nab-paclitaxel/gemcitabine group versus 1% in the gemcitabine group. In the nab-paclitaxel/gemcitabine group, the median time from grade 3 neuropathy to grade 1 or resolution was 29 days. Of patients with grade 3 peripheral neuropathy, 44% were able to resume treatment at a reduced dose within a median of 23 days after onset of a grade 3 event.
    • On the basis of this trial, nab-paclitaxel plus gemcitabine is a standard treatment option for patients with advanced pancreatic cancer.
    • Quality of life data have not yet been published regarding this regimen, and this study does not address the efficacy of nab-paclitaxel/gemcitabine versus FOLFIRINOX.
     
  5. FOLFIRINOX versus gemcitabine: A multicenter phase II/III trial included 342 patients with metastatic pancreatic adenocarcinoma with an ECOG performance status score of 0 or 1.[19][Level of evidence: 1iiA] The patients were randomly assigned to receive FOLFIRINOX (oxaliplatin [85 mg/m2], irinotecan [180 mg/m2], leucovorin [400 mg/m2], and 5-FU [400 mg/m2] given as a bolus followed by 2,400 mg/m2 given as a 46-hour continuous infusion, every 2 weeks) or gemcitabine (1,000 mg/m2 weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks).
    • The median OS was 11.1 months in the FOLFIRINOX group compared with 6.8 months in the gemcitabine group (HRdeath = 0.57; 95% CI, 0.45–0.73; P < .001).
    • Median progression-free survival was 6.4 months in the FOLFIRINOX group and 3.3 months in the gemcitabine group (HR for disease progression = 0.47; 95% CI, 0.37–0.59; P < .001).
    • FOLFIRINOX was more toxic than gemcitabine; 5.4% of patients in this group had febrile neutropenia. At 6 months, 31% of the patients in the FOLFIRINOX group had a definitive degradation of quality of life, versus 66% in the gemcitabine group (HR = 0.47; 95% CI, 0.30–0.70; P < .001).
    • On the basis of this trial, FOLFIRINOX is considered a standard treatment option for patients with advanced pancreatic cancer.
     
  6. 5-FU, leucovorin, and oxaliplatin (OFF regimen) versus best supportive care (BSC): Second-line chemotherapy after progression on a gemcitabine-based regimen may be beneficial. The CONKO-003 investigators randomly assigned patients in the second line of chemotherapy to either the OFF regimen or BSC.[20]; [21][Level of evidence: 3iA] The OFF regimen consisted of leucovorin (200 mg/m2) followed by 5-FU (2,000 mg/m2 [24-hour continuous infusion] on days 1, 8, 15, and 22) and oxaliplatin (85 mg/m2 on days 8 and 22). After a rest of 3 weeks, the next cycle was started on day 43. The trial was terminated early because of poor accrual, and only 46 patients were randomly assigned to either the OFF regimen or BSC.
    • Median survival on second-line chemotherapy was 4.82 months (95% CI, 4.29–5.35) with the OFF treatment regimen and 2.30 months (95% CI, 1.76–2.83) with BSC alone (HR = 0.45; 95% CI, 0.24–0.83).
    • Median OS was 9.09 months for the sequence of gemcitabine (GEM)-OFF and 7.90 months for GEM-BSC.
    • The early closure of the study and the very small number of patients made the P values misleading. Therefore, second-line chemotherapy with the OFF regimen may be falsely associated with improved survival.
     

Treatment Options Under Clinical Evaluation for Stage III Pancreatic Cancer

Treatment options under clinical evaluation include the following:

  1. For patients with unresectable tumors, clinical trials evaluating novel agents in combination with chemotherapy or chemoradiation therapy (RTOG-PA-0020 is one example).
  2. Intraoperative radiation therapy and/or implantation of radioactive sources.[22][23]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III pancreatic cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Iacobuzio-Donahue CA, Fu B, Yachida S, et al.: DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol 27 (11): 1806-13, 2009.

  2. van den Bosch RP, van der Schelling GP, Klinkenbijl JH, et al.: Guidelines for the application of surgery and endoprostheses in the palliation of obstructive jaundice in advanced cancer of the pancreas. Ann Surg 219 (1): 18-24, 1994.

  3. Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001.

  4. Sohn TA, Lillemoe KD, Cameron JL, et al.: Surgical palliation of unresectable periampullary adenocarcinoma in the 1990s. J Am Coll Surg 188 (6): 658-66; discussion 666-9, 1999.

  5. A multi-institutional comparative trial of radiation therapy alone and in combination with 5-fluorouracil for locally unresectable pancreatic carcinoma. The Gastrointestinal Tumor Study Group. Ann Surg 189 (2): 205-8, 1979.

  6. Cohen SJ, Dobelbower R Jr, Lipsitz S, et al.: A randomized phase III study of radiotherapy alone or with 5-fluorouracil and mitomycin-C in patients with locally advanced adenocarcinoma of the pancreas: Eastern Cooperative Oncology Group study E8282. Int J Radiat Oncol Biol Phys 62 (5): 1345-50, 2005.

  7. Chauffert B, Mornex F, Bonnetain F, et al.: Phase III trial comparing initial chemoradiotherapy (intermittent cisplatin and infusional 5-FU) followed by gemcitabine vs. gemcitabine alone in patients with locally advanced non metastatic pancreatic cancer: a FFCD-SFRO study. [Abstract] J Clin Oncol 24 (Suppl 18): A-4008, 180s, 2006.

  8. Loehrer PJ Sr, Feng Y, Cardenes H, et al.: Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol 29 (31): 4105-12, 2011.

  9. Moertel CG, Frytak S, Hahn RG, et al.: Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer 48 (8): 1705-10, 1981.

  10. Chauffert B, Mornex F, Bonnetain F, et al.: Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study. Ann Oncol 19 (9): 1592-9, 2008.

  11. Huguet F, André T, Hammel P, et al.: Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR phase II and III studies. J Clin Oncol 25 (3): 326-31, 2007.

  12. Rothenberg ML, Moore MJ, Cripps MC, et al.: A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann Oncol 7 (4): 347-53, 1996.

  13. Burris HA 3rd, Moore MJ, Andersen J, et al.: Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15 (6): 2403-13, 1997.

  14. Storniolo AM, Enas NH, Brown CA, et al.: An investigational new drug treatment program for patients with gemcitabine: results for over 3000 patients with pancreatic carcinoma. Cancer 85 (6): 1261-8, 1999.

  15. Moore MJ, Goldstein D, Hamm J, et al.: Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25 (15): 1960-6, 2007.

  16. Poplin E, Feng Y, Berlin J, et al.: Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol 27 (23): 3778-85, 2009.

  17. Colucci G, Labianca R, Di Costanzo F, et al.: Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. J Clin Oncol 28 (10): 1645-51, 2010.

  18. Von Hoff DD, Ervin T, Arena FP, et al.: Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369 (18): 1691-703, 2013.

  19. Conroy T, Desseigne F, Ychou M, et al.: FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364 (19): 1817-25, 2011.

  20. Pelzer U, Kubica K, Stieler J, et al.: A randomized trial in patients with gemcitabine refractory pancreatic cancer. Final results of the CONKO 003 study. [Abstract] J Clin Oncol 26 (Suppl 15): A-4508, 2008.

  21. Pelzer U, Schwaner I, Stieler J, et al.: Best supportive care (BSC) versus oxaliplatin, folinic acid and 5-fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: a phase III-study from the German CONKO-study group. Eur J Cancer 47 (11): 1676-81, 2011.

  22. Tepper JE, Noyes D, Krall JM, et al.: Intraoperative radiation therapy of pancreatic carcinoma: a report of RTOG-8505. Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 21 (5): 1145-9, 1991.

  23. Reni M, Panucci MG, Ferreri AJ, et al.: Effect on local control and survival of electron beam intraoperative irradiation for resectable pancreatic adenocarcinoma. Int J Radiat Oncol Biol Phys 50 (3): 651-8, 2001.

Stage IV Pancreatic Cancer Treatment

Treatment Options for Stage IV Pancreatic Cancer

Treatment options for stage IV pancreatic cancer include the following:

  1. Palliative therapy.
  2. Chemotherapy: gemcitabine; gemcitabine and erlotinib; or oxaliplatin, irinotecan, leucovorin, and fluorouracil (5-FU) (FOLFIRINOX).[1][2][3][4][5][6][7][8][9][10]

Palliative therapy

Palliative therapy for advanced pancreatic cancer includes the following:

  1. Pain-relieving procedures (e.g., celiac or intrapleural block) and supportive care.[11]
  2. Palliative surgical biliary bypass, percutaneous radiologic biliary stent placement, or endoscopically placed biliary stents.[12][13][14]

Chemotherapy

The low objective response rate and lack of survival benefit with current chemotherapy indicates that clinical trials are appropriate treatment of all newly diagnosed patients. Occasionally, patients have palliation of symptoms when treated with chemotherapy with well-tested older drugs, such as 5-FU. Gemcitabine has demonstrated activity in patients with pancreatic cancer and is a useful palliative agent.[1][15][16]

Evidence (chemotherapy):

  1. Gemcitabine versus 5-FU: A phase III trial of gemcitabine versus 5-FU as first-line therapy in patients with advanced or metastatic adenocarcinoma of the pancreas reported a significant improvement in survival among patients treated with gemcitabine (1-year survival was 18% with gemcitabine compared with 2% with 5-FU; P = .003).[15][Level of evidence: 1iiA]
  2. Gemcitabine alone versus gemcitabine and erlotinib: The National Cancer Institute of Canada performed a phase III trial (CAN-NCIC-PA3 [NCT00026338]) that compared gemcitabine alone versus the combination of gemcitabine and erlotinib (100 mg/day) in patients with advanced or metastatic pancreatic carcinomas.[17][Level of evidence: 1iiA]
    • The addition of erlotinib modestly prolonged survival when combined with gemcitabine alone (hazard ratio [HR] = 0.81; 95% confidence interval [CI]; P = .038).
    • The corresponding median survival rate for patients receiving erlotinib was 6.2 months, versus 5.9 months for patients receiving placebo. The 1-year survival rate for patients receiving erlotinib was 23%, versus 17% for patients receiving placebo.
     
  3. Platinum analog or fluoropyrimidine versus single-agent gemcitabine: Many phase III studies have evaluated a combination regimen with either a platinum analog (cisplatin or oxaliplatin) or fluoropyrimidine versus single-agent gemcitabine.[18][19]
    • Not one of these phase III trials has demonstrated a statistically significant advantage favoring the use of combination chemotherapy in the first-line treatment of metastatic pancreatic cancer.
     
  4. Gemcitabine and nab-paclitaxel versus gemcitabine: A multicenter, international phase III trial (NCT00844649) included 861 patients with metastatic pancreatic adenocarcinoma (Karnofsky Performance Status of ≥70) who had not previously received chemotherapy for metastatic disease.[20][Level of evidence: 1iiA] Patients who received adjuvant gemcitabine or any other chemotherapy were excluded. The patients were randomly assigned to receive gemcitabine (1,000 mg/m2) and nab-paclitaxel (125 mg/m2 of body-surface area) weekly for 3 of 4 weeks or gemcitabine monotherapy (1,000 mg/m2 weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks).
    • The median OS was 8.5 months in the nab-paclitaxel/gemcitabine group compared with 6.7 months in the gemcitabine group (HRdeath, 0.72; 95% CI, 0.62–0.83; P < .001).
    • Median progression-free survival was 5.5 months in the nab-paclitaxel/gemcitabine group and 3.7 months in the gemcitabine group (HRdisease progression, 0.69; 95% CI, 0.58–0.82, P < .001).
    • Nab-paclitaxel/gemcitabine was more toxic than gemcitabine. The most common grade 3 toxicities were neutropenia (38% in the nab-paclitaxel-gemcitabine group vs. 27% in the gemcitabine group), fatigue (17% in the nab-paclitaxel/gemcitabine group vs. 1% in the gemcitabine group), and neuropathy (17% in the nab-paclitaxel/gemcitabine group vs. 1% in the gemcitabine group). Febrile neutropenia occurred in 3% of the nab-paclitaxel group versus 1% in the gemcitabine group. In the nab-paclitaxel/gemcitabine group, the median time from grade 3 neuropathy to grade 1 or resolution was 29 days. Of patients with grade 3 peripheral neuropathy, 44% were able to resume treatment at a reduced dose within a median of 23 days after onset of a grade 3 event.
    • On the basis of this trial, nab-paclitaxel plus gemcitabine is a standard treatment option for patients with advanced pancreatic cancer.
    • Quality of life data have not yet been published regarding this regimen, and this study does not address the efficacy of nab-paclitaxel-gemcitabine versus FOLFIRINOX.
     
  5. FOLFIRINOX versus gemcitabine: A multicenter phase II/III trial included 342 patients with metastatic pancreatic adenocarcinoma with an Eastern Cooperative Oncology Group performance status score of 0 or 1.[21][Level of evidence: 1iiA] The patients were randomly assigned to receive FOLFIRINOX (oxaliplatin [85 mg/m2], irinotecan [180 mg/m2], leucovorin [400 mg/m2], and 5-FU [400 mg/m2] given as a bolus followed by 2,400 mg/m2 given as a 46-hour continuous infusion, every 2 weeks) or gemcitabine (1,000 mg/m2 weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks).
    • The median overall survival (OS) was 11.1 months in the FOLFIRINOX group compared with 6.8 months in the gemcitabine group (HRdeath = 0.57; 95% CI, 0.45–0.73; P < .001).
    • Median progression-free survival was 6.4 months in the FOLFIRINOX group and 3.3 months in the gemcitabine group (HR for disease progression = 0.47; 95% CI, 0.37–0.59; P < .001).
    • FOLFIRINOX was more toxic than gemcitabine; 5.4% of patients in this group had febrile neutropenia. At 6 months, 31% of the patients in the FOLFIRINOX group had a definitive degradation of quality of life, versus 66% in the gemcitabine group (HR = 0.47; 95% CI, 0.30–0.70; P < .001).
    • On the basis of this trial, FOLFIRINOX is considered a standard treatment option for patients with advanced pancreatic cancer.
     
  6. 5-FU, leucovorin, and oxaliplatin (OFF regimen) versus best supportive care (BSC): Second-line chemotherapy after progression on a gemcitabine-based regimen may be beneficial. The CONKO-003 investigators randomly assigned patients in the second line of chemotherapy to either an OFF regimen or BSC.[22]; [23][Level of evidence: 3iA] The OFF regimen consisted of leucovorin (200 mg/m2) followed by 5-FU (2,000 mg/m2 [24 hours continuous infusion] on days 1, 8, 15, and 22) and oxaliplatin (85 mg/m2 on days 8 and 22). After a rest of 3 weeks, the next cycle was started on day 43. The trial was terminated early because of poor accrual, and only 46 patients were randomly assigned to either the OFF regimen or BSC.
    • Median survival on second-line chemotherapy was 4.82 months (95% CI, 4.29–5.35) for the OFF-regimen treatment and 2.30 months (95% CI, 1.76–2.83) with BSC alone (HR = 0.45; 95% CI, 0.24–0.83).
    • Median OS was 9.09 months for the sequence of gemcitabine (GEM)-OFF and 7.90 months for GEM-BSC.
    • The early closure of the study and the very small number of patients made the P values misleading. Therefore, second-line chemotherapy with the OFF regimen may be erroneously associated with improved survival.
     

Treatment Options Under Clinical Evaluation for Stage IV Pancreatic Cancer

Treatment options under clinical evaluation include the following:

  1. Clinical trials evaluating new anticancer agents alone or in combination with chemotherapy.[2][3][4][5][6][7][9][24][25][26][27][28][29]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV pancreatic cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Rothenberg ML, Moore MJ, Cripps MC, et al.: A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann Oncol 7 (4): 347-53, 1996.

  2. MacDonald JS, Widerlite L, Schein PS: Biology, diagnosis, and chemotherapeutic management of pancreatic malignancy. Adv Pharmacol Chemother 14: 107-42, 1977.

  3. Bukowski RM, Balcerzak SP, O'Bryan RM, et al.: Randomized trial of 5-fluorouracil and mitomycin C with or without streptozotocin for advanced pancreatic cancer. A Southwest Oncology Group study. Cancer 52 (9): 1577-82, 1983.

  4. DeCaprio JA, Mayer RJ, Gonin R, et al.: Fluorouracil and high-dose leucovorin in previously untreated patients with advanced adenocarcinoma of the pancreas: results of a phase II trial. J Clin Oncol 9 (12): 2128-33, 1991.

  5. Kelsen D, Hudis C, Niedzwiecki D, et al.: A phase III comparison trial of streptozotocin, mitomycin, and 5-fluorouracil with cisplatin, cytosine arabinoside, and caffeine in patients with advanced pancreatic carcinoma. Cancer 68 (5): 965-9, 1991.

  6. O'Connell MJ: Current status of chemotherapy for advanced pancreatic and gastric cancer. J Clin Oncol 3 (7): 1032-9, 1985.

  7. Crown J, Casper ES, Botet J, et al.: Lack of efficacy of high-dose leucovorin and fluorouracil in patients with advanced pancreatic adenocarcinoma. J Clin Oncol 9 (9): 1682-6, 1991.

  8. Carmichael J, Fink U, Russell RC, et al.: Phase II study of gemcitabine in patients with advanced pancreatic cancer. Br J Cancer 73 (1): 101-5, 1996.

  9. Haller DG: Chemotherapy for advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 56 (4 Suppl): 16-23, 2003.

  10. Kulke MH, Blaszkowsky LS, Ryan DP, et al.: Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. J Clin Oncol 25 (30): 4787-92, 2007.

  11. Polati E, Finco G, Gottin L, et al.: Prospective randomized double-blind trial of neurolytic coeliac plexus block in patients with pancreatic cancer. Br J Surg 85 (2): 199-201, 1998.

  12. van den Bosch RP, van der Schelling GP, Klinkenbijl JH, et al.: Guidelines for the application of surgery and endoprostheses in the palliation of obstructive jaundice in advanced cancer of the pancreas. Ann Surg 219 (1): 18-24, 1994.

  13. Sohn TA, Lillemoe KD, Cameron JL, et al.: Surgical palliation of unresectable periampullary adenocarcinoma in the 1990s. J Am Coll Surg 188 (6): 658-66; discussion 666-9, 1999.

  14. Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001.

  15. Burris HA 3rd, Moore MJ, Andersen J, et al.: Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15 (6): 2403-13, 1997.

  16. Storniolo AM, Enas NH, Brown CA, et al.: An investigational new drug treatment program for patients with gemcitabine: results for over 3000 patients with pancreatic carcinoma. Cancer 85 (6): 1261-8, 1999.

  17. Moore MJ, Goldstein D, Hamm J, et al.: Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25 (15): 1960-6, 2007.

  18. Poplin E, Feng Y, Berlin J, et al.: Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol 27 (23): 3778-85, 2009.

  19. Colucci G, Labianca R, Di Costanzo F, et al.: Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. J Clin Oncol 28 (10): 1645-51, 2010.

  20. Von Hoff DD, Ervin T, Arena FP, et al.: Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369 (18): 1691-703, 2013.

  21. Conroy T, Desseigne F, Ychou M, et al.: FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364 (19): 1817-25, 2011.

  22. Pelzer U, Kubica K, Stieler J, et al.: A randomized trial in patients with gemcitabine refractory pancreatic cancer. Final results of the CONKO 003 study. [Abstract] J Clin Oncol 26 (Suppl 15): A-4508, 2008.

  23. Pelzer U, Schwaner I, Stieler J, et al.: Best supportive care (BSC) versus oxaliplatin, folinic acid and 5-fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: a phase III-study from the German CONKO-study group. Eur J Cancer 47 (11): 1676-81, 2011.

  24. Rougier P, Adenis A, Ducreux M, et al.: A phase II study: docetaxel as first-line chemotherapy for advanced pancreatic adenocarcinoma. Eur J Cancer 36 (8): 1016-25, 2000.

  25. Bramhall SR, Rosemurgy A, Brown PD, et al.: Marimastat as first-line therapy for patients with unresectable pancreatic cancer: a randomized trial. J Clin Oncol 19 (15): 3447-55, 2001.

  26. Stathopoulos GP, Mavroudis D, Tsavaris N, et al.: Treatment of pancreatic cancer with a combination of docetaxel, gemcitabine and granulocyte colony-stimulating factor: a phase II study of the Greek Cooperative Group for Pancreatic Cancer. Ann Oncol 12 (1): 101-3, 2001.

  27. Feliu J, López Alvarez MP, Jaraiz MA, et al.: Phase II trial of gemcitabine and UFT modulated by leucovorin in patients with advanced pancreatic carcinoma. The ONCOPAZ Cooperative Group. Cancer 89 (8): 1706-13, 2000.

  28. Rocha Lima CM, Savarese D, Bruckner H, et al.: Irinotecan plus gemcitabine induces both radiographic and CA 19-9 tumor marker responses in patients with previously untreated advanced pancreatic cancer. J Clin Oncol 20 (5): 1182-91, 2002.

  29. Smith D, Gallagher N: A phase II/III study comparing intravenous ZD9331 with gemcitabine in patients with pancreatic cancer. Eur J Cancer 39 (10): 1377-83, 2003.

Recurrent Pancreatic Cancer Treatment

Treatment Options for Recurrent Pancreatic Cancer

Treatment options for recurrent pancreatic cancer include the following:

  1. Palliative therapy.
  2. Chemotherapy: fluorouracil [1] or gemcitabine.[2][3][4]

Palliative therapy

Palliative therapy for recurrent pancreatic cancer includes the following:

  1. Palliative surgical bypass procedures such as endoscopic or radiologically placed stents.[5][6]
  2. Palliative radiation procedures.
  3. Pain relief by celiac axis nerve or intrapleural block (percutaneous).[7]
  4. Other palliative medical care alone.

Chemotherapy

Chemotherapy occasionally produces objective antitumor response, but the low percentage of significant responses and lack of survival advantage warrant use of therapies under evaluation.[8]

Treatment Options Under Clinical Evaluation for Recurrent Pancreatic Cancer

Treatment options under clinical evaluation include the following:

  1. Phase I and II clinical trials evaluating pharmacologic modulation of fluorinated pyrimidines, new anticancer agents, or biological agents.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent pancreatic cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Cullinan SA, Moertel CG, Fleming TR, et al.: A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma. Fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin. JAMA 253 (14): 2061-7, 1985.

  2. Rothenberg ML, Moore MJ, Cripps MC, et al.: A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann Oncol 7 (4): 347-53, 1996.

  3. Burris HA 3rd, Moore MJ, Andersen J, et al.: Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15 (6): 2403-13, 1997.

  4. Storniolo AM, Enas NH, Brown CA, et al.: An investigational new drug treatment program for patients with gemcitabine: results for over 3000 patients with pancreatic carcinoma. Cancer 85 (6): 1261-8, 1999.

  5. Sohn TA, Lillemoe KD, Cameron JL, et al.: Surgical palliation of unresectable periampullary adenocarcinoma in the 1990s. J Am Coll Surg 188 (6): 658-66; discussion 666-9, 1999.

  6. Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001.

  7. Polati E, Finco G, Gottin L, et al.: Prospective randomized double-blind trial of neurolytic coeliac plexus block in patients with pancreatic cancer. Br J Surg 85 (2): 199-201, 1998.

  8. Royal RE, Wolfe RA, Crane CH: Cancer of the pancreas. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 961-89.


This information is provided by the National Cancer Institute.

This information was last updated on February 21, 2014.


 
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