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 behind the stomach and in front of 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 produce juices that help digest (break down) food.
  • To produce 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 produced by exocrine pancreas cells and the hormones are produced by endocrine pancreas cells. About 95% of pancreatic cancers begin in exocrine cells.

This summary provides information on exocrine pancreatic cancer. See the PDQ summary on Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment for information on endocrine pancreatic cancer.

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.
  • Long-standing diabetes.
  • Chronicpancreatitis.
  • Certain hereditaryconditions, such as hereditary pancreatitis, multiple endocrine neoplasia type 1 syndrome, hereditary nonpolyposis colon cancer (HNPCC; Lynch syndrome), von Hippel-Lindau syndrome, ataxia-telangiectasia, and the familial atypical multiple mole melanoma syndrome (FAMMM).

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

These and other symptoms may be caused by pancreatic cancer. 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).
  • Pain in the upper or middle abdomen and back.
  • Weight loss for no known reason.
  • Loss of appetite.
  • Fatigue.

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 produce 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. Other instruments may be inserted through the same or other incisions to perform procedures such as removing organs or taking tissue samples for biopsy.
  • 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 (a surgical incision made in the wall of the abdomen).

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 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.

There are three ways that cancer spreads in the body.

The three ways that cancer spreads in the body are:

  • Through tissue. Cancer invades the surrounding normal tissue.
  • Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body.
  • Through the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body.

When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary (metastatic) tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone 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:

  • 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.

Patients with pancreatic cancer have special nutritional needs.

Surgery to remove the pancreas may interfere with the production of 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.

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

A link to a list of current clinical trials is included for each treatment section. For some types or stages of cancer, there may not be any trials listed. Check with your doctor for clinical trials that are not listed here but may be right for you.

Stages I and II Pancreatic Cancer

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

  • Surgery with or without chemotherapy.
  • Surgery with chemotherapy and radiation therapy.
  • A clinical trial of combination chemotherapy.
  • A clinical trial of chemotherapy and targeted therapy (erlotinib), 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. 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 (gemcitabine) with or without targeted therapy (erlotinib).
  • Combination chemotherapy.
  • Chemoradiation followed by chemotherapy.
  • Chemotherapy followed by chemoradiation, for cancer that has not spread to other parts of the body.
  • 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. 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:

  • Chemotherapy (gemcitabine) with or without targeted therapy (erlotinib).
  • Combination chemotherapy.
  • Palliative treatments for pain, such as nerve blocks, and other supportive care.
  • Palliative surgery or stent placement to bypass blocked areas in ducts or the small intestine.
  • 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. 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:

  • Chemotherapy.
  • Palliativesurgery or stent placement to bypass blocked areas in ducts or the small intestine.
  • Palliative radiation therapy.
  • Other palliative medical care to reduce symptoms, such as nerve blocks to relieve pain.
  • 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. 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:

About PDQ

PDQ is a comprehensive cancer database available on NCI's Web site.

PDQ is the National Cancer Institute's (NCI's) comprehensive cancer information database. Most of the information contained in PDQ is available online at NCI's Web site. PDQ is provided as a service of the NCI. The NCI is part of the National Institutes of Health, the federal government's focal point for biomedical research.

PDQ contains cancer information summaries.

The PDQ database contains summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative medicine. Most summaries are available in two versions. The health professional versions provide detailed information written in technical language. The patient versions are written in easy-to-understand, nontechnical language. Both versions provide current and accurate cancer information.

Images in the PDQ summaries are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in the PDQ summaries, along with many other cancer-related images, are available in Visuals Online, a collection of over 2,000 scientific images.

The PDQ cancer information summaries are developed by cancer experts and reviewed regularly.

Editorial Boards made up of experts in oncology and related specialties are responsible for writing and maintaining the cancer information summaries. The summaries are reviewed regularly and changes are made as new information becomes available. The date on each summary ("Date Last Modified") indicates the time of the most recent change.

PDQ also contains information on clinical trials.

A clinical trial is a study to answer a scientific question, such as whether one treatment is better than another. Trials are based on past studies and what has been learned in the laboratory. Each trial answers certain scientific questions in order to find new and better ways to help cancer patients. During treatment clinical trials, information is collected about the effects of a new treatment and how well it works. If a clinical trial shows that a new treatment is better than one currently being used, the new treatment may become "standard." 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.

Listings of clinical trials are included in PDQ and are available online at NCI's Web site. Descriptions of the trials are available in health professional and patient versions. Many cancer doctors who take part in clinical trials are also listed in PDQ. For more information, call the Cancer Information Service 1-800-4-CANCER (1-800-422-6237).


This information is provided by the National Cancer Institute.

This information was last updated on January 23, 2013.


General Information About Pancreatic Cancer

Incidence and Mortality

Estimated new cases and deaths from pancreatic cancer in the United States in 2013:[1]

  • New cases: 45,220.
  • Deaths: 38,460.

Carcinoma of the pancreas has had a markedly increased incidence during 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] Cancer of the exocrine pancreas is rarely curable and has an overall survival (OS) rate of less than 4%.[3] The highest cure rate occurs if the tumor is truly localized to the pancreas; however, this stage of the disease accounts for fewer than 20% of cases. For those 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 can yield actuarial 5-year survival rates of 18% to 24%.[4][Level of evidence: 3iA] Improvements in imaging technology, including spiral computed tomographic scans, magnetic resonance imaging scans, positron emission tomographic scans, endoscopic ultrasound examination, and laparoscopic staging can aid in the diagnosis and the identification of patients with disease that is not amenable to resection.[5] 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.[6] For patients with advanced cancers, the OS rate of all stages is less than 1% at 5 years with most patients dying within 1 year.[7][8][9][10]

No tumor-specific markers exist for pancreatic cancer; markers such as serum 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.[11][Level of evidence: 3iDiii] The presence of a normal CA 19-9, however, does not preclude recurrence.

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. Palliation of symptoms, however, may be achieved with conventional treatment. Symptoms caused by pancreatic cancer may depend on the site of the tumor within the pancreas and the degree of involvement. Palliative surgical or radiologic biliary decompression, relief of gastric outlet obstruction, and pain control may improve the quality of life while not affecting OS.[12][13] Palliative efforts may also be directed to the potentially disabling psychological events associated with the diagnosis and treatment of pancreatic cancer.[14] (Refer to the PDQ summary on Pain for more information.)

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

Related Summary

Another PDQ summary containing information related to pancreatic cancer includes:

  • Unusual Cancers of Childhood (pancreatic cancer in children)

References:

  1. American Cancer Society.: Cancer Facts and Figures 2013. Atlanta, Ga: American Cancer Society, 2013. Available online. Last accessed February 8, 2013.

  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. Greenlee RT, Murray T, Bolden S, et al.: Cancer statistics, 2000. CA Cancer J Clin 50 (1): 7-33, 2000 Jan-Feb.

  4. 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.

  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. 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.

  7. Lillemoe KD: Current management of pancreatic carcinoma. Ann Surg 221 (2): 133-48, 1995.

  8. Yeo CJ: Pancreatic cancer: 1998 update. J Am Coll Surg 187 (4): 429-42, 1998.

  9. Nitecki SS, Sarr MG, Colby TV, et al.: Long-term survival after resection for ductal adenocarcinoma of the pancreas. Is it really improving? Ann Surg 221 (1): 59-66, 1995.

  10. 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.

  11. 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.

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

Borderline Malignancies

  • Mucinous cystic tumor with dysplasia.
  • Intraductal papillary mucinous tumor with dysplasia.[3]
  • 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 that of resectable and unresectable is uncertain since state-of-the-art treatment has demonstrated little impact on survival. To communicate a uniform definition of disease, however, knowledge of the extent of the disease is necessary. 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.

Definitions of TNM

The American Joint Committee on Cancer has designated staging by TNM classification to define pancreatic cancer.[1]

Table 1. Primary Tumor (T)a

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).

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 "PanInIII" classification.

Table 2. Regional Lymph Nodes (N)a

NX

Regional lymph nodes cannot be assessed.

N0

No regional lymph node metastasis.

N1

Regional lymph node 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.

Table 3. Distant Metastasis (M)a

M0

No distant 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.

Table 4. Anatomic Stage/Prognostic Groupsa

Stage

T

N

M

0

Tis

N0

M0

IA

T1

N0

M0

IB

T2

N0

M0

IIA

T3

N0

M0

IIB

T1

N1

M0

T2

N1

M0

T3

N1

M0

III

T4

Any N

M0

IV

Any T

Any N

M1

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.

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

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 prior to selecting palliative approaches. To provide optimal palliation, determination of resectability must be made. Staging studies for resectability include helical computed tomographic scan, magnetic resonance imaging scan, and endoscopic ultrasound. The introduction of minimally invasive techniques, such as laparoscopy and laparoscopic ultrasound, may decrease the use of laparotomy.[1][2] Surgical resection remains the primary modality when feasible since, on occasion, resection can lead to long-term survival and provides effective palliation.[3][4][5][Level of evidence: 3iA] 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.[6][7][8][9][10] 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.) 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.)

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

References:

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

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

  8. 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.

  9. 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.

  10. 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 II Pancreatic Cancer

Approximately 20% of patients present with pancreatic cancer amenable to local surgical resection with operative mortality rates of approximately 1% to 16%.[1][2][3][4][5] 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).[1] 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.[6][7][8][Level of evidence: 3iA] The role of postoperative therapy (chemotherapy with or without chemoradiation therapy [CRT]) in the management of this disease remains controversial because much of the randomized clinical trial data available are statistically underpowered and provide conflicting results.[9][10][11][12][13]

Three phase III trials prior to 2000 examined the potential overall survival (OS) benefit of postoperative adjuvant 5-fluorouracil (5-FU)–based CRT. A small randomized trial conducted by the Gastrointestinal Study Group (GITSG) in 1985 demonstrated 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.[9][Level of evidence: 1iiA];[10][Level of evidence: 2A] An attempt by the European Organization for the Research and Treatment of Cancer to reproduce the results of the GITSG trial failed to confirm a significant benefit for adjuvant CRT over resection alone;[11][Level of evidence: 1iiA] however, this trial treated patients with pancreatic as well as periampullary cancers (with a potential better prognosis). A subset analysis of the patients with primary pancreatic tumors indicated a trend towards improved median, 2-year, and 5-year OS with adjuvant therapy compared with surgery alone (17.1 months, 37% and 20% vs. 12.6 months, 23% and 10%, P = .09 for median survival).

An updated analysis of a subsequent European Study for Pancreatic Cancer (ESPAC 1) trial examined only patients who underwent strict randomization following pancreatic resection. The patients were assigned to one of four groups (observation, bolus 5-FU chemotherapy, bolus 5-FU CRT, or CRT followed by additional chemotherapy). 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. These results were difficult to interpret, however, 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.[12][13][14][Level of evidence: 1iiA]

The United States Gastrointestinal Intergroup has reported the results of a randomized phase III trial (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.[15] The primary endpoints were OS for all patients and OS for patients with pancreatic head cancers.

The median OS for the 388 patients with pancreatic head tumors was 20.5 months in the gemcitabine arm versus 16.9 months in the 5-FU arm; 3-year survival was 31% versus 22%, respectively (P = .09; hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.65–1.03). OS for all patients was not reported in the publication; however, median survival estimates extrapolated from the presented survival curve were approximately 19 months for the gemcitabine group and 17 months for the 5-FU group.[15][Level of evidence: 1iiA]

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 six cycles of adjuvant gemcitabine versus observation.[16] 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, 11.4–15.3) and 6.9 months in the observation group (95% CI, 6.1–7.8; P < .001). However, there was no significant difference in OS between the gemcitabine arm (median 22.1 months, 95% CI, 18.4–25.8) and the control group (median 20.2 months, 95% CI, 17–23.4).[16][Level of evidence: 1iiDii] At the American Society of Clinical Oncology annual meeting in 2008, the investigators, with longer follow-up, reported a significant improvement in OS that favored gemcitabine (median survival 22.8 months vs. 20.2 months, P = .005; 5-year survival 21% vs. 9%).[17]

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 folinic acid (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.[18] Median OS was 23.0 months (95% CI, 21.1– 25.0) for patients treated with 5-FU plus folinic acid 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).[18][Level of evidence: 1iiA]

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

Standard treatment options:

  1. Radical pancreatic resection:
    • Whipple procedure (pancreaticoduodenal resection).
    • Total pancreatectomy when necessary for adequate margins.
    • Distal pancreatectomy for tumors of the body and tail of the pancreas.[19][20]
  2. Radical pancreatic resection with postoperative chemotherapy (gemcitabine or 5-FU/folinic acid).[18]
  3. Radical pancreatic resection with postoperative 5-FU chemotherapy and radiation therapy.[9][10][11][12][13]

Treatment options under clinical evaluation:

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

  2. 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.

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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

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

  11. 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.

  12. 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.

  13. 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.

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

  15. 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.

  16. 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.

  17. Neuhaus P, Riess H, Post S, et al.: CONKO-001: final results of the randomized, prospective, multicenter phase III trial of adjuvant chemotherapy with gemcitabine versus observation in patients with resected pancreatic cancer (PC). [Abstract] J Clin Oncol 26 (Suppl 15): A-LBA4504, 2008.

  18. 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.

  19. 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.

  20. 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.

Stage III Pancreatic Cancer

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.[1] A significant proportion of patients approaching one-third of all patients with pancreatic cancer will present with stage III or locally advanced disease. 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.[2][Level of evidence: 1iiA] Therefore, investigators have struggled with the question of whether chemoradiation for patients presenting with stage III disease is worthwhile.

Table 5. Randomized Studies in Stage III Pancreatic Cancer: Median Survival

Trial

Regimen

Chemoradiation

Radiation Alone

Chemotherapy Alone

P Value

Pre-2000

GITSG[3]

Radiation alone vs. 5-FU/60 Gy XRT

40 weeks

20 weeks

<.01

ECOG[4]

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

8.4 months

7.1 months

.16

Post-2000

FFCD[5]

GEM vs. GEM, cisplatin, 60 Gy XRT

8.6 months

13 months

.03

ECOG[6]

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.

Prior to 2000, several phase III trials evaluated combined modality therapy versus radiation therapy alone. Prior to 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 to receive concurrent EBRT (either 40 Gy or 60 Gy) plus bolus fluorouracil (5-FU).[3][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 with 40 Gy and 36% for patients who received chemoradiation 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 to the 40 Gy arm.[7] In contrast, investigators from the ECOG randomly assigned 114 patients to radiation therapy (59.4 Gy) alone or with concurrent infusional 5-FU (1,000 mg/m2 daily on days 2 through 5 and days 28 through 31) plus mitomycin (10 mg/m2 on day 2) and found no difference in OS between the two groups.[4]

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 through 5 for 6 weeks and 20 mg/m2/day of cisplatin on days 1 through 5 during weeks 1 and 5) or induction gemcitabine (1,000 mg/m2 weekly for 7 weeks).[8][Level of evidence: 1iiA] Maintenance gemcitabine was administered to both groups until stopped by disease progression or treatment discontinuation as a result of toxicity. 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 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 arm because of a greater incidence of grade 3 to 4 hematological toxicities (71% vs. 27%, P = .0001). As a result of this study, induction chemoradiation has fallen out of favor.

The results of the FFCD study stand in contrast to the results of a study from ECOG where investigators randomly assigned 74 patients to either gemcitabine alone or gemcitabine with radiation followed by gemcitabine.[6] Of note, the study was closed early as the result of poor accrual. The primary endpoint was survival, which was 9.2 months (95% 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). Grade 4 and 5 toxicity was greater in the chemoradiation arm than in the chemotherapy arm (41% vs. 9%).

Given the increased toxicity of chemoradiation 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. With this strategy, the selected patients have an absence of progressive disease locally or systemically after several months of chemotherapy. A retrospective analysis of 181 patients enrolled in prospective phase II and III GERCOR studies revealed that 29% had metastatic disease after three months of gemcitabine-based chemotherapy. For the remaining 71%, median OS was significantly longer among patients treated with chemoradiation compared to additional chemotherapy (15.0 months vs. 11.7 months, P = .0009).[9][Level of evidence: 3iiiA] 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 options:

Gemcitabine has demonstrated activity in patients with pancreatic cancer and is a useful palliative agent.[10][11][12] 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 as compared with 2% with 5-FU, P = .003).[11][Level of evidence: 1iiA]

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. They showed that the addition of erlotinib modestly prolonged survival when combined with gemcitabine versus gemcitabine alone (hazard ratio [HR], 0.81; 95% CI, P = .038).[13] 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.[13][Level of evidence: 1iiA]

Many phase III studies have evaluated a combination regimen with either a platinum analogue (cisplatin or oxaliplatin) or fluoropyrimidine versus single-agent gemcitabine.[14][15] 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.

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.[16] The patients were randomly assigned to receive FOLFIRINOX (oxaliplatin [85 mg/m2], irinotecan [180 mg/m2], leucovorin [400 mg/m2], and fluorouracil [400 mg/m2] given as a bolus followed by 2400 mg/m2 given as a 46-hour continuous infusion, every 2 weeks) or gemcitabine (1000 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 (HR for death, 0.57; 95% CI, 0.45–0.73; P < .001).[16][Level of evidence: 1iiA] 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). The objective response rate was 31.6% in the FOLFIRINOX group versus 9.4% in the gemcitabine group (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 the quality of life versus 66% in the gemcitabine group (HR, 0.47; 95% CI, 0.30–0.70; P < .001). Therefore, FOLFIRINOX is considered a standard treatment option for patients with advanced pancreatic cancer.

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 a regimen of 5-FU, leucovorin, and oxaliplatin (OFF regimen) or best supportive care (BSC).[17][18] The OFF regimen consisted of folinic acid (200 mg/m2) followed by 5-FU (2 g/m2 [24 hours] 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 second-line survival 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).[18][Level of evidence: 3iA] Median OS was 9.09 months for the sequence of gemcitabine/5-FU, leucovorin, and oxaliplatin or GEM-OFF and 7.90 months for gemcitabine/best supportive care or 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 associated with improved survival.

Standard treatment options:

  1. Palliative surgical biliary and/or gastric bypass, percutaneous radiologic biliary stent placement, or endoscopic biliary stent placement.[19][20]
  2. Chemotherapy with gemcitabine, gemcitabine and erlotinib, or FOLFIRINOX.
  3. Chemoradiation followed by chemotherapy.
  4. Chemotherapy followed by chemoradiation for patients without metastatic disease.

Treatment options under clinical evaluation:

  1. For patients with technically 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.[21][22]

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. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

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

  17. 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.

  18. 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.

  19. 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.

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

  21. 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.

  22. 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

The low objective response rate and lack of survival benefit with current chemotherapy indicates clinical trials as appropriate treatment of all newly diagnosed patients. Occasional patients have palliation of symptoms when treated by chemotherapy with well-tested older drugs such as fluorouracil (5-FU). Gemcitabine has demonstrated activity in patients with pancreatic cancer and is a useful palliative agent.[1][2][3] 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 as compared with 2% with 5-FU, P = .003).[2][Level of evidence: 1iiA] 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. They showed that the addition of erlotinib modestly prolonged survival when combined with gemcitabine alone (hazard ratio [HR], 0.81; 95% confidence interval [CI], P = .038).[4] 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.[4][Level of evidence: 1iiA]

Many phase III studies have evaluated a combination regimen with either a platinum analogue (cisplatin or oxaliplatin) or fluoropyrimidine versus single-agent gemcitabine.[5][6] 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.

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.[7] The patients were randomly assigned to receive FOLFIRINOX (oxaliplatin [85 mg/m2], irinotecan [180 mg/m2], leucovorin [400 mg/m2], and fluorouracil [400 mg/m2] given as a bolus followed by 2400 mg/m2 given as a 46-hour continuous infusion, every 2 weeks) or gemcitabine (1000 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 (HR for death, 0.57; 95% CI, 0.45–0.73; P < .001).[7][Level of evidence: 1iiA] 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). The objective response rate was 31.6% in the FOLFIRINOX group versus 9.4% in the gemcitabine group (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 the quality of life versus 66% in the gemcitabine group (HR, 0.47; 95% CI, 0.30–0.70; P < .001). Therefore, FOLFIRINOX is now considered a standard treatment option for patients with advanced pancreatic cancer.

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 a regimen of 5-FU, leucovorin, and oxaliplatin (OFF regimen) or best supportive care (BSC).[8][9] The OFF regimen consisted of folinic acid (200 mg/m2) followed by 5-FU (2 g/m2 [24 hours] 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 second-line survival 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).[9][Level of evidence: 3iA] Median OS was 9.09 months for the sequence of gemcitabine/5-FU, leucovorin, and oxaliplatin or GEM-OFF and 7.90 months for gemcitabine/best supportive care or 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 associated with improved survival.

Standard treatment options:

  1. Chemotherapy with gemcitabine, gemcitabine and erlotinib, or FOLFIRINOX.[1][10][11][12][13][14][15][16][17][18]
  2. Pain-relieving procedures (e.g., celiac or intrapleural block) and supportive care.[19]
  3. Palliative surgical biliary bypass, percutaneous radiologic biliary stent placement, or endoscopically placed biliary stents.[20][21][22]

Treatment options under clinical evaluation:

  • Clinical trials evaluating new anticancer agents alone or in combination with chemotherapy.[10][11][12][13][14][15][17][23][24][25][26][27][28]

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. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

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

  8. 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.

  9. 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.

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

  11. 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.

  12. 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.

  13. 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.

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

  15. 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.

  16. 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.

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

  18. 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.

  19. 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.

  20. 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.

  21. 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.

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

  23. 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.

  24. 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.

  25. 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.

  26. 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.

  27. 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.

  28. 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

Chemotherapy occasionally produces objective antitumor response, but the low percentage of significant responses and lack of survival advantage warrant use of therapies under evaluation.[1]

Standard treatment options:

  1. Chemotherapy with fluorouracil [2] or gemcitabine.[3][4][5]
  2. Palliative surgical bypass procedures, such as endoscopic or radiologically placed stents.[6][7]
  3. Palliative radiation procedures.
  4. Pain relief by celiac axis nerve or intrapleural block (percutaneous).[8]
  5. Other palliative medical care alone.

Treatment options under clinical evaluation:

  • Clinical trials evaluating pharmacologic modulation of fluorinated pyrimidines, new anticancer agents, or biologicals (phase I and II).

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. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

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

  8. 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.


This information is provided by the National Cancer Institute.

This information was last updated on February 14, 2013.


 
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