Purpose of This PDQ Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of gastric cancer. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.

Information about the following is included in this summary:

• Risk factors.
• Cellular classification.
• Staging.
• Treatment options by cancer stage.

This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.

This summary is available in a patient version, written in less technical language, and in Spanish.

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General Information About Gastric Cancer

Related Summaries

Other PDQ summaries containing information related to gastric cancer include:

• Unusual Cancers of Childhood.
• Gastric Cancer Prevention.
• Gastric Cancer Screening.

Statistics

Estimated new cases and deaths from gastric cancer in the United States in 2009:[1]

• New cases: 21,130.
• Deaths: 10,620.

Epidemiology

Management of adenocarcinoma histology, which accounts for 90% to 95% of all gastric malignancies, is discussed in this summary. The site of cancer origin within the stomach has changed in frequency in the United States over recent decades.[2] Cancer of the distal half of the stomach has been decreasing in the United States since the 1930s. However, in the last 2 decades, the incidence of cancer of the cardia and gastroesophageal junction has been rapidly rising. The incidence of this cancer has increased dramatically, especially in patients younger than 40 years.

Risk Factors

In the United States, gastric cancer ranks 14th in incidence among the major types of cancer malignancies. While the precise etiology is unknown, acknowledged risk factors for gastric cancer include:[3][4][5]

• Helicobacter pylori gastric infection.
• Advanced age.
• Male gender.
• Diet low in fruits and vegetables.
• Diet high in salted, smoked, or preserved foods.
• Chronic atrophic gastritis.
• Intestinal metaplasia.
• Pernicious anemia.
• Gastric adenomatous polyps.
• Family history of gastric cancer.
• Cigarette smoking.
• Menetrier disease (giant hypertrophic gastritis).
• Familial adenomatous polyposis.

Prognosis

The prognosis of patients with gastric cancer is related to tumor extent and includes both nodal involvement and direct tumor extension beyond the gastric wall.[6][7] Tumor grade may also provide some prognostic information.[8]

In localized distal gastric cancer, more than 50% of patients can be cured. However, early-stage disease accounts for only 10% to 20% of all cases diagnosed in the United States. The remaining patients present with metastatic disease in either regional or distant sites. The overall survival rate in these patients at 5 years ranges from almost no survival for patients with disseminated disease to almost 50% survival for patients with localized distal gastric cancers confined to resectable regional disease. Even with apparent localized disease, the 5-year survival rate of patients with proximal gastric cancer is only 10% to 15%. Although the treatment of patients with disseminated gastric cancer may result in palliation of symptoms and some prolongation of survival, long remissions are uncommon.

Gastrointestinal stromal tumors occur most commonly in the stomach. (Refer to the PDQ summary on Adult Soft Tissue Sarcoma Treatment for more information.)

References:

1. American Cancer Society.: Cancer Facts and Figures 2009. Atlanta, Ga: American Cancer Society, 2009. Also available online. Last accessed January 6, 2010.

2. Blot WJ, Devesa SS, Kneller RW, et al.: Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 265 (10): 1287-9, 1991.  

3. Kurtz RC, Sherlock P: The diagnosis of gastric cancer. Semin Oncol 12 (1): 11-8, 1985.  

4. Scheiman JM, Cutler AF: Helicobacter pylori and gastric cancer. Am J Med 106 (2): 222-6, 1999.  

5. Fenoglio-Preiser CM, Noffsinger AE, Belli J, et al.: Pathologic and phenotypic features of gastric cancer. Semin Oncol 23 (3): 292-306, 1996.  

6. Siewert JR, Böttcher K, Stein HJ, et al.: Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study. Ann Surg 228 (4): 449-61, 1998.  

7. Nakamura K, Ueyama T, Yao T, et al.: Pathology and prognosis of gastric carcinoma. Findings in 10,000 patients who underwent primary gastrectomy. Cancer 70 (5): 1030-7, 1992.  

8. Adachi Y, Yasuda K, Inomata M, et al.: Pathology and prognosis of gastric carcinoma: well versus poorly differentiated type. Cancer 89 (7): 1418-24, 2000.  

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Cellular Classification of Gastric Cancer

There are two major types of gastric adenocarcinoma:

• Intestinal.
• Diffuse.

Intestinal adenocarcinomas are well differentiated, and the cells tend to arrange themselves in tubular or glandular structures. The terms tubular, papillary, and mucinous are assigned to the various types of intestinal adenocarcinomas. Rarely, adenosquamous cancers can occur.

Diffuse adenocarcinomas are undifferentiated or poorly differentiated, and they lack a gland formation. Clinically, diffuse adenocarcinomas can give rise to infiltration of the gastric wall (i.e., linitis plastica).

Some tumors can have mixed features of intestinal and diffuse types.

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Stage Information for Gastric Cancer

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification.[1][2][3]

TNM Definitions

Primary tumor (T)  

• TX: Primary tumor cannot be assessed
• T0: No evidence of primary tumor
• Tis: Carcinoma in situ: intraepithelial tumor without invasion of the lamina propria
• T1: Tumor invades lamina propria or submucosa
• T2: Tumor invades the muscularis propria or the subserosa*
  • T2a: Tumor invades muscularis propria
  • T2b: Tumor invades subserosa
   
• T3: Tumor penetrates the serosa (visceral peritoneum) without invading adjacent structures**^,***
• T4: Tumor invades adjacent structures**^,***

*A tumor may penetrate the muscularis propria with extension into the gastrocolic or gastrohepatic ligaments, or into the greater or lesser omentum, without perforation of the visceral peritoneum covering these structures. In this case, the tumor is classified T2. If there is perforation of the visceral peritoneum covering the gastric ligaments or the omentum, the tumor should be classified T3.

**The adjacent structures of the stomach include the spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine, and retroperitoneum.

***Intramural extension to the duodenum or esophagus is classified by the depth of greatest invasion in any of these sites, including stomach.

Regional lymph nodes (N)  

The regional lymph nodes are the perigastric nodes, found along the lesser and greater curvatures, and the nodes located along the left gastric, common hepatic, splenic, and celiac arteries. For pN, a regional lymphadenectomy specimen will ordinarily contain at least 15 lymph nodes. Involvement of other intra-abdominal lymph nodes, such as the hepatoduodenal, retropancreatic, mesenteric, and para-aortic, is classified as distant metastasis.

• NX: Regional lymph node(s) cannot be assessed
• N0: No regional lymph node metastasis*
• N1: Metastasis in one to six regional lymph nodes
• N2: Metastasis in 7 to 15 regional lymph nodes
• N3: Metastasis in more than 15 regional lymph nodes

*A designation of pN0 should be used if all examined lymph nodes are negative, regardless of the total number removed and examined.

Distant metastasis (M)  

• MX: Distant metastasis cannot be assessed
• M0: No distant metastasis
• M1: Distant metastasis

AJCC Stage Groupings

Stage 0

• Tis, N0, M0

Stage IA

• T1, N0, M0

Stage IB

• T1, N1, M0
• T2a, N0, M0
• T2b, N0, M0

Stage II

• T1, N2, M0
• T2a, N1, M0
• T2b, N1, M0
• T3, N0, M0

Stage IIIA

• T2a, N2, M0
• T2b, N2, M0
• T3, N1, M0
• T4, N0, M0

Stage IIIB

• T3, N2, M0

Stage IV

• T4, N1, M0
• T4, N2, M0
• T4, N3, M0
• T1, N3, M0
• T2, N3, M0
• T3, N3, M0
• Any T, any N, M1

References:

1. Stomach. In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 99-106.  

2. Roder JD, Böttcher K, Busch R, et al.: Classification of regional lymph node metastasis from gastric carcinoma. German Gastric Cancer Study Group. Cancer 82 (4): 621-31, 1998.  

3. Ichikura T, Tomimatsu S, Uefuji K, et al.: Evaluation of the New American Joint Committee on Cancer/International Union against cancer classification of lymph node metastasis from gastric carcinoma in comparison with the Japanese classification. Cancer 86 (4): 553-8, 1999.  

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Treatment Option Overview

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Radical surgery represents the standard form of therapy that has curative intent. However, the incidences of local failure in the tumor bed and regional lymph nodes, and distant failures via hematogenous or peritoneal routes, remain high.[1] As such, adjuvant external-beam radiation therapy with combined chemotherapy has been evaluated in the United States.

In a phase III Intergroup trial (INT-0116), 556 patients with completely resected stage IB to stage IV (M0) adenocarcinoma of the stomach and gastroesophageal junction were randomly assigned to receive surgery alone or surgery plus postoperative chemotherapy (5-fluorouracil [5-FU] and leucovorin) and concurrent radiation therapy (45 Gy). With 5 years' median follow-up, a significant survival benefit was reported for patients who received adjuvant combined modality therapy.[2][Level of evidence: 1iiA] Median survival was 36 months for the adjuvant chemoradiation therapy group as compared to 27 months for the surgery-alone arm (P = .005). Three-year overall survival (OS) rates and relapse-free survival rates were 50% and 48%, respectively, with adjuvant chemoradiation therapy versus 41% and 31%, respectively, for surgery alone (P = .005). The rate of distant metastases was 32% for the surgery-alone arm and 40% for the chemoradiation therapy arm. Because distant disease remains a significant concern, the aim of the current Cancer and Leukemia Group B study (CALGB-80101) is to augment the postoperative chemoradiation regimen used in INT-0116. Neoadjuvant chemoradiation therapy such as in the RTOG-9904 trial also remains under clinical evaluation in the SWOG-S0425 trial.[3]

Investigators in Europe evaluated the role of preoperative and postoperative chemotherapy without radiation therapy.[4] In the randomized phase III trial (MRC-ST02), patients with stage II or higher adenocarcinoma of the stomach or of the lower third of the esophagus were assigned to receive three cycles of epirubicin, cisplatin, and continuous infusion 5-FU before and after surgery or to receive surgery alone. Compared with the surgery group, the perioperative chemotherapy group had a significantly higher likelihood of progression-free survival (hazard ratio [HR] for progression, 0.66; 95% confidence interval [CI], 0.53–0.81; P < .001) and of OS (HR for death, 0.75; 95% CI, 0.60–0.93; P = .009). Five-year OS was 36.3%; 95% CI, 29 to 43 for the perioperative chemotherapy group and 23%; 95% CI, 16.6 to 29.4 for the surgery group.[4][Level of evidence: 1iiA]

References:

1. Gunderson LL, Sosin H: Adenocarcinoma of the stomach: areas of failure in a re-operation series (second or symptomatic look) clinicopathologic correlation and implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 8 (1): 1-11, 1982.  

2. Macdonald JS, Smalley SR, Benedetti J, et al.: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345 (10): 725-30, 2001.  

3. Ajani JA, Winter K, Okawara GS, et al.: Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol 24 (24): 3953-8, 2006.  

4. Cunningham D, Allum WH, Stenning SP, et al.: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355 (1): 11-20, 2006.  

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Stage 0 Gastric Cancer

Standard treatment options:  

• Surgery.

Stage 0 is gastric cancer confined to mucosa. Experience in Japan, where stage 0 is diagnosed frequently, indicates that more than 90% of patients treated by gastrectomy with lymphadenectomy will survive beyond 5 years. An American series has confirmed these results.[1]

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage 0 gastric 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. Green PH, O'Toole KM, Slonim D, et al.: Increasing incidence and excellent survival of patients with early gastric cancer: experience in a United States medical center. Am J Med 85 (5): 658-61, 1988.  

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Stage I Gastric Cancer

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Standard treatment options:  

1. One of the following surgical procedures:
   • Distal subtotal gastrectomy (if the lesion is not in the fundus or at the cardioesophageal junction).
   • Proximal subtotal gastrectomy or total gastrectomy, both with distal esophagectomy (if the lesion involves the cardia). These tumors often involve the submucosal lymphatics of the esophagus.
   • Total gastrectomy (if the tumor involves the stomach diffusely or arises in the body of the stomach and extends to within 6 cm of the cardia or distal antrum).

   Regional lymphadenectomy is recommended with all of the above procedures. Splenectomy is not routinely performed.[1]

2. Postoperative chemoradiation therapy for patients with node-positive (T1 N1) and muscle-invasive (T2 N0) disease.[2]

Surgical resection including regional lymphadenectomy is the treatment of choice for patients with stage I gastric cancer.[1] If the lesion is not in the cardioesophageal junction and does not diffusely involve the stomach, subtotal gastrectomy is the procedure of choice, since it has been demonstrated to provide equivalent survival when compared with total gastrectomy and is associated with decreased morbidity.[3][Level of evidence: 1iiA] When the lesion involves the cardia, proximal subtotal gastrectomy or total gastrectomy (including a sufficient length of esophagus) may be performed with curative intent. If the lesion diffusely involves the stomach, total gastrectomy is required. At a minimum, surgical resection should include greater and lesser curvature perigastric regional lymph nodes. Note that in patients with stage I gastric cancer, perigastric lymph nodes may contain cancer.

In patients with node-positive (T1 N1) and muscle-invasive (T2 N0) disease, postoperative chemoradiation therapy may be considered. A prospective multi-institution phase III trial (INT-0116) evaluating postoperative combined chemoradiation therapy versus surgery alone in 556 patients with completely resected stage IB to stage IV (M0) adenocarcinoma of the stomach and gastroesophageal junction reported a significant survival benefit with adjuvant combined modality therapy.[2][Level of evidence: 1iiA] With a median follow-up of 5 years, median survival was 36 months for the adjuvant chemoradiation therapy group as compared to 27 months for the surgery-alone arm (P = .005). Three-year overall survival and relapse-free survival rates were 50% and 48% with adjuvant chemoradiation therapy versus 41% and 31% for surgery alone (P = .005). However, only 36 patients in the trial had stage IB tumors (18 patients in each arm).[4] Since the prognosis is relatively favorable for patients with completely resected stage IB disease, the effectiveness of adjuvant chemoradiation therapy for this group is less clear.

Treatment options under clinical evaluation:  

• Neoadjuvant chemoradiation therapy such as in the SWOG-S0425 and RTOG-9904 trials.[5]

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage I gastric 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. Brennan MF, Karpeh MS Jr: Surgery for gastric cancer: the American view. Semin Oncol 23 (3): 352-9, 1996.  

2. Macdonald JS, Smalley SR, Benedetti J, et al.: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345 (10): 725-30, 2001.  

3. Bozzetti F, Marubini E, Bonfanti G, et al.: Subtotal versus total gastrectomy for gastric cancer: five-year survival rates in a multicenter randomized Italian trial. Italian Gastrointestinal Tumor Study Group. Ann Surg 230 (2): 170-8, 1999.  

4. Kelsen DP: Postoperative adjuvant chemoradiation therapy for patients with resected gastric cancer: intergroup 116. J Clin Oncol 18 (21 Suppl): 32S-4S, 2000.  

5. Ajani JA, Winter K, Okawara GS, et al.: Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol 24 (24): 3953-8, 2006.  

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Stage II Gastric Cancer

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Standard treatment options:  

1. One of the following surgical procedures:
   • Distal subtotal gastrectomy (if the lesion is not in the fundus or at the cardioesophageal junction).
   • Proximal subtotal gastrectomy or total gastrectomy (if the lesion involves the cardia).
   • Total gastrectomy (if the tumor involves the stomach diffusely or arises in the body of the stomach and extends to within 6 cm of the cardia).

   Regional lymphadenectomy is recommended with all of the above procedures. Splenectomy is not routinely performed.[1]

2. Postoperative chemoradiation therapy.[2]
3. Perioperative chemotherapy.[3]

Surgical resection with regional lymphadenectomy is the treatment of choice for patients with stage II gastric cancer.[1] If the lesion is not in the cardioesophageal junction and does not diffusely involve the stomach, subtotal gastrectomy is the procedure of choice. When the lesion involves the cardia, proximal subtotal gastrectomy or total gastrectomy may be performed with curative intent. If the lesion diffusely involves the stomach, total gastrectomy and appropriate lymph node resection may be required. The role of extended lymph node (D2) dissection is uncertain [4] and in some series is associated with increased morbidity.[5][6]

Postoperative chemoradiation therapy may be considered for patients with stage II gastric cancer. A prospective multi-institution phase III trial (INT-0116) evaluating postoperative combined chemoradiation therapy versus surgery alone in 556 patients with completely resected stage IB to stage IV (M0) adenocarcinoma of the stomach and gastroesophageal junction reported a significant survival benefit with adjuvant combined modality therapy.[2][Level of evidence: 1iiA] With a median follow-up of 5 years, median survival was 36 months for the adjuvant chemoradiation therapy group as compared to 27 months for the surgery-alone arm (P = .005). Three-year overall survival (OS) and relapse-free survival rates were 50% and 48%, respectively, with adjuvant chemoradiation therapy versus 41% and 31%, respectively, for surgery alone (P = .005).The rate of distant metastases was 32% for the surgery-alone arm and 40% for the chemoradiation therapy arm. Because distant disease remains a significant concern, the aim of the current Cancer and Leukemia Group B study (CALGB-80101) is to augment the postoperative chemoradiation regimen used in INT-0116.[7] Neoadjuvant chemoradiation therapy remains under clinical evaluation such as in the SWOG-S0425 and RTOG-9904 trials.[8]

Investigators in Europe evaluated the role of preoperative and postoperative chemotherapy without radiation therapy.[3] In the randomized phase III trial (MRC-ST02), patients with stage II or higher adenocarcinoma of the stomach or of the lower third of the esophagus were assigned to receive three cycles of epirubicin, cisplatin, and continuous infusion fluorouracil (ECF) before and after surgery or to receive surgery alone. Compared with the surgery group, the perioperative chemotherapy group had a significantly higher likelihood of progression-free survival (hazard ratio [HR] for progression, 0.66; 95% confidence interval [CI], 0.53–0.81; P < .001) and of OS (HR for death, 0.75; 95% CI, 0.60–0.93; P = .009). Five-year OS was 36.3%, 95% CI, 29 to 43 for the perioperative chemotherapy group and 23%, 95% CI, 16.6 to 29.4 for the surgery group.[3][Level of evidence: 1iiA]

Treatment options under clinical evaluation:  

1. Postoperative chemoradiation therapy with ECF as evidenced in the CALGB-80101 trial.[7]
2. Neoadjuvant chemoradiation therapy as evidenced in the SWOG-S0425 and RTOG-9904 trials.[8]

All newly diagnosed patients with stage II gastric cancer should be considered candidates for clinical trials.

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage II gastric 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. Brennan MF, Karpeh MS Jr: Surgery for gastric cancer: the American view. Semin Oncol 23 (3): 352-9, 1996.  

2. Macdonald JS, Smalley SR, Benedetti J, et al.: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345 (10): 725-30, 2001.  

3. Cunningham D, Allum WH, Stenning SP, et al.: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355 (1): 11-20, 2006.  

4. Kitamura K, Yamaguchi T, Sawai K, et al.: Chronologic changes in the clinicopathologic findings and survival of gastric cancer patients. J Clin Oncol 15 (12): 3471-80, 1997.  

5. Bonenkamp JJ, Songun I, Hermans J, et al.: Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients. Lancet 345 (8952): 745-8, 1995.  

6. Cuschieri A, Fayers P, Fielding J, et al.: Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial.The Surgical Cooperative Group. Lancet 347 (9007): 995-9, 1996.  

7. Fuchs C, Tepper JE, Niedwiecki D, et al.: Postoperative adjuvant chemoradiation for gastric or gastroesophageal adenocarcinoma using epirubicin, cisplatin, and infusional (CI) 5-FU (ECF) before and after CI 5-FU and radiotherapy (RT): interim toxicity results from Intergroup trial CALGB 80101. [Abstract] American Society of Clinical Oncology 2006 Gastrointestinal Cancers Symposium, 26-28 January 2006, San Francisco, California. A-61, 2006.  

8. Ajani JA, Winter K, Okawara GS, et al.: Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol 24 (24): 3953-8, 2006.  

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Stage III Gastric Cancer

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Standard treatment options:  

1. Radical surgery. Curative resection procedures are confined to patients who at the time of surgical exploration do not have extensive nodal involvement.
2. Postoperative chemoradiation therapy.[1]
3. Perioperative chemotherapy.[2]

All patients with tumors that can be resected should undergo surgery. As many as 15% of selected stage III patients can be cured by surgery alone, particularly if lymph node involvement is minimal (<7 lymph nodes).

Postoperative chemoradiation therapy may be considered for patients with stage III gastric cancer. A prospective multi-institution phase III trial (INT-0116) evaluating postoperative combined chemoradiation therapy versus surgery alone in 556 patients with completely resected stage IB to stage IV (M0) adenocarcinoma of the stomach and gastroesophageal junction reported a significant survival benefit with adjuvant combined modality therapy.[1][Level of evidence: 1iiA] With a median follow-up of 5 years, median survival was 36 months for the adjuvant chemoradiation therapy group as compared to 27 months for the surgery-alone arm (P = .005). Three-year overall survival (OS) and relapse-free survival rates were 50% and 48%, respectively, with adjuvant chemoradiation therapy versus 41% and 31%, respectively, for surgery alone (P = .005). Because distant disease remains a significant concern, the aim of the current Cancer and Leukemia Group B study (CALGB-80101) is to augment the postoperative chemoradiation regimen used in the INT-0116 trial , for example, and the preoperative chemotherapy and chemoradiation therapy regimen used in the RTOG-9904 trial, as another example.

Investigators in Europe evaluated the role of preoperative and postoperative chemotherapy without radiation therapy.[2] In the randomized phase III trial (MRC-ST02), patients with stage II or higher adenocarcinoma of the stomach or of the lower third of the esophagus were assigned to receive three cycles of epirubicin, cisplatin, and continuous infusion 5-fluorouracil (ECF) before and after surgery or to receive surgery alone. Compared with the surgery group, the perioperative chemotherapy group had a significantly higher likelihood of progression-free survival (hazard ratio [HR] for progression, 0.66; 95% confidence interval [CI], 0.53–0.81; P < .001) and of OS (HR for death, 0.75; 95% CI, 0.60–0.93; P = .009). Five-year OS was 36.3%; 95% CI, 29 to 43 for the perioperative chemotherapy group and 23%; 95% CI, 16.6 to 29.4 for the surgery group.[2][Level of evidence: 1iiA]

Treatment options under clinical evaluation:  

1. Postoperative chemoradiation with ECF such as in the CALGB-80101 trial.[3].
2. Neoadjuvant chemoradiation therapy such as in the SWOG-S0425 and RTOG-9904 trials.[4]

All newly diagnosed patients with stage III gastric cancer should be considered candidates for clinical trials.

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage III gastric 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. Macdonald JS, Smalley SR, Benedetti J, et al.: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345 (10): 725-30, 2001.  

2. Cunningham D, Allum WH, Stenning SP, et al.: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355 (1): 11-20, 2006.  

3. Fuchs C, Tepper JE, Niedwiecki D, et al.: Postoperative adjuvant chemoradiation for gastric or gastroesophageal adenocarcinoma using epirubicin, cisplatin, and infusional (CI) 5-FU (ECF) before and after CI 5-FU and radiotherapy (RT): interim toxicity results from Intergroup trial CALGB 80101. [Abstract] American Society of Clinical Oncology 2006 Gastrointestinal Cancers Symposium, 26-28 January 2006, San Francisco, California. A-61, 2006.  

4. Ajani JA, Winter K, Okawara GS, et al.: Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol 24 (24): 3953-8, 2006.  

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Stage IV Gastric Cancer

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Treatment Options for Patients With No Distant Metastases (M0)

Standard treatment options:  

1. Radical surgery. Curative resection procedures are confined to patients who at the time of surgical exploration do not have extensive nodal involvement.
2. Postoperative chemoradiation therapy.[1]
3. Perioperative chemotherapy.[2]

All patients with tumors that can be resected should undergo surgery. As many as 15% of selected stage IV patients can be cured by surgery alone, particularly if lymph node involvement is minimal (<7 lymph nodes).

Postoperative chemoradiation therapy may be considered for patients with stage IV gastric cancer. A prospective multi-institution phase III trial (INT-0116) evaluating postoperative combined chemoradiation therapy versus surgery alone in 556 patients with completely resected stage IB to stage IV (M0) adenocarcinoma of the stomach and gastroesophageal junction reported a significant survival benefit with adjuvant combined modality therapy.[1][Level of evidence: 1iiA] With a median follow-up of 5 years, median survival was 36 months for the adjuvant chemoradiation therapy group as compared to 27 months for the surgery-alone arm (P = .005). Three-year overall survival (OS) and relapse-free survival rates were 50% and 48%, respectively, with adjuvant chemoradiation therapy versus 41% and 31%, respectively, for surgery alone (P = .005). Because distant disease remains a significant concern, the aim of the current Cancer and Leukemia Group B study (CALGB-80101) is to augment the postoperative chemoradiation regimen used in the INT-0116trial, for example, and the preoperative chemotherapy and chemoradiation therapy regimen used in the RTOG-9904 trial.

Investigators in Europe evaluated the role of preoperative and postoperative chemotherapy without radiation therapy.[2] In the randomized phase III trial (MRC-ST02), patients with stage II or higher adenocarcinoma of the stomach or of the lower third of the esophagus were assigned to receive three cycles of epirubicin, cisplatin, and continuous infusion 5-fluorouracil (ECF) before and after surgery or to receive surgery alone. Compared with the surgery group, the perioperative chemotherapy group had a significantly higher likelihood of progression-free survival (hazard ratio [HR] for progression, 0.66; 95% confidence interval [CI], 0.53–0.81; P < .001) and of OS (HR for death, 0.75; 95% CI, 0.60–0.93; P = .009). Five-year OS was 36.3%; 95% CI, 29 to 43 for the perioperative chemotherapy group and 23%; 95% CI, 16.6 to 29.4 for the surgery group.[2][Level of evidence: 1iiA]

Treatment options under clinical evaluation:  

1. Postoperative chemoradiation with ECF such as in the CALGB-80101 trial.[3].
2. Neoadjuvant chemoradiation therapy such as in the SWOG-S0425 and RTOG-9904 trials.[4]

All newly diagnosed patients with stage IV gastric cancer should be considered candidates for clinical trials.

Treatment Options for Patients With Distant Metastases (M1)

Standard treatment options:  

1. Palliative chemotherapy with:
   • Fluorouracil (5-FU).[5][6][7]
   • Epirubicin, cisplatin, and 5-FU (ECF).[8][9]
   • Cisplatin and 5-FU (CF).[10][7]
   • Etoposide, leucovorin, and 5-FU (ELF).[11]
   • 5-FU, doxorubicin, and methotrexate (FAMTX).[10]
    
2. Endoluminal laser therapy or endoluminal stent placement may be helpful to patients whose tumors have occluded the gastric inlet or outlet.[12]
3. Palliative radiation therapy may alleviate bleeding, pain, and obstruction.
4. Palliative resection should be reserved for patients with continued bleeding or obstruction.

Standard chemotherapy versus best supportive care for patients with metastatic gastric cancer has been tested in several clinical trials, and there is general agreement that patients who receive chemotherapy live for several months longer on average than patients who receive supportive care.[13][14][15][Level of evidence: 1iiA] During the last 20 years, multiple randomized studies evaluating different treatment regimens (monotherapy vs. combination chemotherapy) have been performed in patients with metastatic gastric cancer with no clear consensus emerging as to the best management approach. A meta-analysis of these studies demonstrated an HR of 0.83 for OS (95% CI, 0.74–0.93) in favor of combination chemotherapy.[16]

Of all the combination regimens, ECF is often considered the reference standard in the United States and Europe. In one European trial, 274 patients with metastatic esophagogastric cancer were randomly assigned to receive either ECF or FAMTX.[17] The group who received ECF had a significantly longer median survival (8.9 vs. 5.7 months, P = .0009) than the FAMTX group.[17][Level of evidence: 1iiA] In a second trial that compared ECF with mitomycin, cisplatin, and 5-FU (MCF), there was no statistically significant difference in median survival (9.4 vs. 8.7 months, P = .315).[9][Level of evidence: 1iiA]

An international collaboration of investigators randomly assigned 445 patients with metastatic gastric cancer to receive docetaxel, cisplatin, and 5-FU (DCF) or CF.[18] Time-to-treatment progression (TTP) was the primary endpoint. Patients who received DCF experienced a significantly longer TTP (5.6 months; 95% CI, 4.9–5.9; vs. 3.7 months; 95% CI, 3.4–4.5; HR, 1.47; 95% CI, 1.19–1.82; log-rank P < .001; risk reduction 32%). The median OS was significantly longer for patients who received DCF versus patients who received CF (9.2 months; 95% CI, 8.4–10.6; vs. 8.6 months; 95% CI, 7.2–9.5; HR, 1.29; 95% CI, 1.0–1.6; log-rank P = .02; risk reduction = 23%).[18][Level of evidence: 1iiA] There were high toxicity rates in both arms.[19] Febrile neutropenia was more common in patients who received DCF (29% vs. 12%), and the death rate on the study was 10.4% for patients on the DCF arm and 9.4% for patients on the CF arm.

Whether the CF regimen should be considered as an index regimen for the treatment of patients with metastatic gastric cancer is the subject of debate.[19] The results of a study that randomly assigned 245 patients with metastatic gastric cancer to receive CF, FAMTX, or ELF demonstrated no significant difference in response rate, progression-free survival, or OS between the arms.[10] Grades 3 and 4 neutropenia occurred in 35% to 43% of patients on all arms, but severe nausea and vomiting was more common in patients in the CF arm and occurred in 26% of those patients.[10][Level of evidence: 1iiDiv]

Treatment options under clinical evaluation:  

• Palliative chemotherapy with:
  • Irinotecan and cisplatin.
  • Folic acid, 5-FU, and irinotecan (FOLFIRI).
  • Leucovorin, 5-FU, and oxaliplatin (FOLFOX).
   

Phase II studies evaluating irinotecan-based or oxaliplatin-based regimens demonstrate similar response rates and TTP to those found with ECF or CF, but the former may be less toxic.[20][21][22][23][24][25] There are conflicting data regarding relative efficacy of any one regimen for another. Ongoing studies are evaluating these newer regimens.

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage IV gastric 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. Macdonald JS, Smalley SR, Benedetti J, et al.: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345 (10): 725-30, 2001.  

2. Cunningham D, Allum WH, Stenning SP, et al.: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355 (1): 11-20, 2006.  

3. Fuchs C, Tepper JE, Niedwiecki D, et al.: Postoperative adjuvant chemoradiation for gastric or gastroesophageal adenocarcinoma using epirubicin, cisplatin, and infusional (CI) 5-FU (ECF) before and after CI 5-FU and radiotherapy (RT): interim toxicity results from Intergroup trial CALGB 80101. [Abstract] American Society of Clinical Oncology 2006 Gastrointestinal Cancers Symposium, 26-28 January 2006, San Francisco, California. A-61, 2006.  

4. Ajani JA, Winter K, Okawara GS, et al.: Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol 24 (24): 3953-8, 2006.  

5. Comis RL, Carter SK: Integration of chemotherapy into combined modality treatment of solid tumors. III. Gastric cancer. Cancer Treat Rev 1 (3): 221-238, 1974.  

6. 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.  

7. Ohtsu A, Shimada Y, Shirao K, et al.: Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol 21 (1): 54-9, 2003.  

8. Waters JS, Norman A, Cunningham D, et al.: Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial. Br J Cancer 80 (1-2): 269-72, 1999.  

9. Ross P, Nicolson M, Cunningham D, et al.: Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol 20 (8): 1996-2004, 2002.  

10. Vanhoefer U, Rougier P, Wilke H, et al.: Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: A trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol 18 (14): 2648-57, 2000.  

11. Ajani JA, Ota DM, Jackson DE: Current strategies in the management of locoregional and metastatic gastric carcinoma. Cancer 67 (1 Suppl): 260-5, 1991.  

12. Ell C, Hochberger J, May A, et al.: Coated and uncoated self-expanding metal stents for malignant stenosis in the upper GI tract: preliminary clinical experiences with Wallstents. Am J Gastroenterol 89 (9): 1496-500, 1994.  

13. Murad AM, Santiago FF, Petroianu A, et al.: Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer 72 (1): 37-41, 1993.  

14. Pyrhönen S, Kuitunen T, Nyandoto P, et al.: Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer 71 (3): 587-91, 1995.  

15. Glimelius B, Ekström K, Hoffman K, et al.: Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol 8 (2): 163-8, 1997.  

16. Wagner AD, Grothe W, Haerting J, et al.: Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol 24 (18): 2903-9, 2006.  

17. Webb A, Cunningham D, Scarffe JH, et al.: Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 15 (1): 261-7, 1997.  

18. Ajani JA, Moiseyenko VM, Tjulandin S, et al.: Clinical benefit with docetaxel plus fluorouracil and cisplatin compared with cisplatin and fluorouracil in a phase III trial of advanced gastric or gastroesophageal cancer adenocarcinoma: the V-325 Study Group. J Clin Oncol 25 (22): 3205-9, 2007.  

19. Ilson DH: Docetaxel, cisplatin, and fluorouracil in gastric cancer: does the punishment fit the crime? J Clin Oncol 25 (22): 3188-90, 2007.  

20. Ilson DH, Saltz L, Enzinger P, et al.: Phase II trial of weekly irinotecan plus cisplatin in advanced esophageal cancer. J Clin Oncol 17 (10): 3270-5, 1999.  

21. Beretta E, Di Bartolomeo M, Buzzoni R, et al.: Irinotecan, fluorouracil and folinic acid (FOLFIRI) as effective treatment combination for patients with advanced gastric cancer in poor clinical condition. Tumori 92 (5): 379-83, 2006 Sep-Oct.  

22. Pozzo C, Barone C, Szanto J, et al.: Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study. Ann Oncol 15 (12): 1773-81, 2004.  

23. Bouché O, Raoul JL, Bonnetain F, et al.: Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol 22 (21): 4319-28, 2004.  

24. Ajani JA, Baker J, Pisters PW, et al.: CPT-11 plus cisplatin in patients with advanced, untreated gastric or gastroesophageal junction carcinoma: results of a phase II study. Cancer 94 (3): 641-6, 2002.  

25. Cavanna L, Artioli F, Codignola C, et al.: Oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic gastric cancer (MGC). Am J Clin Oncol 29 (4): 371-5, 2006.  

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Recurrent Gastric Cancer

Standard treatment options:  

1. Palliative chemotherapy with:
   • Fluorouracil (5-FU).[1][2][3]
   • Epirubicin, cisplatin, and 5-FU (ECF).[4][5]
   • Cisplatin and 5-FU (CF).[6][3]
   • Etoposide, leucovorin, and 5-FU (ELF).[7]
   • 5-FU, doxorubicin, and methotrexate (FAMTX).[6]
    
2. Endoluminal laser therapy or endoluminal stent placement may be helpful to patients whose tumors have occluded the gastric inlet or outlet.[8]
3. Palliative radiation therapy may alleviate bleeding, pain, and obstruction.
4. Palliative resection should be reserved for patients with continued bleeding or obstruction.

Standard chemotherapy versus best supportive care for patients with metastatic gastric cancer has been tested in several clinical trials, and there is general agreement that patients who receive chemotherapy live for several months longer on average than patients who receive supportive care.[9][10][11][Level of evidence: 1iiA] During the last 20 years, multiple randomized studies evaluating different treatment regimens (monotherapy vs. combination chemotherapy) have been performed in patients with metastatic gastric cancer with no clear consensus emerging as to the best management approach. A meta-analysis of these studies demonstrated an HR of 0.83 for OS (95% CI, 0.74–0.93) in favor of combination chemotherapy.[12]

Of all the combination regimens, ECF is often considered the reference standard in the United States and Europe. In one European trial, 274 patients with metastatic esophagogastric cancer were randomly assigned to receive either ECF or FAMTX.[13] The group who received ECF had a significantly longer median survival (8.9 vs. 5.7 months, P = .0009) than the FAMTX group.[13][Level of evidence: 1iiA] In a second trial that compared ECF with mitomycin, cisplatin, and 5FU (MCF), there was no statistically significant difference in median survival (9.4 vs. 8.7 months, P = .315).[5][Level of evidence: 1iiA]

An international collaboration of investigators randomly assigned 445 patients with metastatic gastric cancer to receive docetaxel, cisplatin, and 5-FU (DCF) or CF.[14] Time-to-treatment progression (TTP) was the primary endpoint. Patients who received DCF experienced a significantly longer TTP (5.6 months; 95% CI, 4.9–5.9; vs. 3.7 months; 95% CI, 3.4–4.5; HR, 1.47; 95% CI, 1.19–1.82; log-rank P < .001; risk reduction 32%). The median OS was significantly longer for patients who received DCF versus patients who received CF (9.2 months; 95% CI, 8.4–10.6; vs. 8.6 months; 95% CI, 7.2–9.5; HR, 1.29; 95% CI, 1.0–1.6; log-rank P = .02; risk reduction = 23%).[14][Level of evidence: 1iiA] There were high toxicity rates in both arms.[15] Febrile neutropenia was more common in patients who received DCF (29% vs. 12%), and the death rate on the study was 10.4% for patients on the DCF arm and 9.4% for patients on the CF arm.

Whether the CF regimen should be considered as an index regimen for the treatment of patients with metastatic gastric cancer is the subject of debate.[15] The results of a study that randomly assigned 245 patients with metastatic gastric cancer to receive CF, FAMTX, or ELF demonstrated no significant difference in response rate, progression-free survival, or OS between the arms.[6] Grades 3 and 4 neutropenia occurred in 35% to 43% of patients on all arms, but severe nausea and vomiting was more common in patients in the CF arm and occurred in 26% of those patients.[6][Level of evidence: 1iiDiv]

Treatment options under clinical evaluation:  

• Palliative chemotherapy with:
  • Irinotecan and cisplatin.
  • Folic acid, 5 FU, and irinotecan (FOLFIRI).
  • Leucovorin, 5 FU, and oxaliplatin (FOLFOX).
   

Phase II studies evaluating irinotecan-based or oxaliplatin-based regimens demonstrate similar response rates and TTP to those found with ECF or CF, but the former may be less toxic.[16][17][18][19][20][21] There are conflicting data regarding relative efficacy of any one regimen over another. Ongoing studies are evaluating these newer regimens.

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent gastric 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. Comis RL, Carter SK: Integration of chemotherapy into combined modality treatment of solid tumors. III. Gastric cancer. Cancer Treat Rev 1 (3): 221-238, 1974.  

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. Ohtsu A, Shimada Y, Shirao K, et al.: Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol 21 (1): 54-9, 2003.  

4. Waters JS, Norman A, Cunningham D, et al.: Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial. Br J Cancer 80 (1-2): 269-72, 1999.  

5. Ross P, Nicolson M, Cunningham D, et al.: Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol 20 (8): 1996-2004, 2002.  

6. Vanhoefer U, Rougier P, Wilke H, et al.: Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: A trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol 18 (14): 2648-57, 2000.  

7. Ajani JA, Ota DM, Jackson DE: Current strategies in the management of locoregional and metastatic gastric carcinoma. Cancer 67 (1 Suppl): 260-5, 1991.  

8. Ell C, Hochberger J, May A, et al.: Coated and uncoated self-expanding metal stents for malignant stenosis in the upper GI tract: preliminary clinical experiences with Wallstents. Am J Gastroenterol 89 (9): 1496-500, 1994.  

9. Murad AM, Santiago FF, Petroianu A, et al.: Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer 72 (1): 37-41, 1993.  

10. Pyrhönen S, Kuitunen T, Nyandoto P, et al.: Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer 71 (3): 587-91, 1995.  

11. Glimelius B, Ekström K, Hoffman K, et al.: Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol 8 (2): 163-8, 1997.  

12. Wagner AD, Grothe W, Haerting J, et al.: Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol 24 (18): 2903-9, 2006.  

13. Webb A, Cunningham D, Scarffe JH, et al.: Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 15 (1): 261-7, 1997.  

14. Ajani JA, Moiseyenko VM, Tjulandin S, et al.: Clinical benefit with docetaxel plus fluorouracil and cisplatin compared with cisplatin and fluorouracil in a phase III trial of advanced gastric or gastroesophageal cancer adenocarcinoma: the V-325 Study Group. J Clin Oncol 25 (22): 3205-9, 2007.  

15. Ilson DH: Docetaxel, cisplatin, and fluorouracil in gastric cancer: does the punishment fit the crime? J Clin Oncol 25 (22): 3188-90, 2007.  

16. Ilson DH, Saltz L, Enzinger P, et al.: Phase II trial of weekly irinotecan plus cisplatin in advanced esophageal cancer. J Clin Oncol 17 (10): 3270-5, 1999.  

17. Beretta E, Di Bartolomeo M, Buzzoni R, et al.: Irinotecan, fluorouracil and folinic acid (FOLFIRI) as effective treatment combination for patients with advanced gastric cancer in poor clinical condition. Tumori 92 (5): 379-83, 2006 Sep-Oct.  

18. Pozzo C, Barone C, Szanto J, et al.: Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study. Ann Oncol 15 (12): 1773-81, 2004.  

19. Bouché O, Raoul JL, Bonnetain F, et al.: Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol 22 (21): 4319-28, 2004.  

20. Ajani JA, Baker J, Pisters PW, et al.: CPT-11 plus cisplatin in patients with advanced, untreated gastric or gastroesophageal junction carcinoma: results of a phase II study. Cancer 94 (3): 641-6, 2002.  

21. Cavanna L, Artioli F, Codignola C, et al.: Oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic gastric cancer (MGC). Am J Clin Oncol 29 (4): 371-5, 2006.  

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More Information

About PDQ  

• PDQ® - NCI's Comprehensive Cancer Database.
  • Full description of the NCI PDQ database.
   

Additional PDQ Summaries  

• PDQ® Cancer Information Summaries: Adult Treatment
  • Treatment options for adult cancers.
   
• PDQ® Cancer Information Summaries: Pediatric Treatment
  • Treatment options for childhood cancers.
   
• PDQ® Cancer Information Summaries: Supportive and Palliative Care
  • Side effects of cancer treatment, management of cancer-related complications and pain, and psychosocial concerns.
   
• PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer)
  • Tests or procedures that detect specific types of cancer.
   
• PDQ® Cancer Information Summaries: Prevention
  • Risk factors and methods to increase chances of preventing specific types of cancer.
   
• PDQ® Cancer Information Summaries: Genetics
  • Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.
   
• PDQ® Cancer Information Summaries: Complementary and Alternative Medicine
  • Information about complementary and alternative forms of treatment for patients with cancer.
   

Important:  

This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

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This information is provided by the National Cancer Institute.

This information was last updated on July 2, 2009.