RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known if surgery alone or surgery combined with chemotherapy is more effective in treating stomach cancer.

PURPOSE: Randomizedphase III trial to compare the effectiveness of surgery with or without combination chemotherapy in treating patients who have stage II, stage III, or stage IV stomach cancer.

Condition	Treatment or Intervention	Phase
stage II gastric cancer stage III gastric cancer stage IV gastric cancer intestinal adenocarcinoma of the stomach diffuse adenocarcinoma of the stomach mixed adenocarcinoma of the stomach	Drug: cisplatin  Drug: fluorouracil  Drug: leucovorin calcium  Procedure: chemotherapy  Procedure: neoadjuvant therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare overall survival in patients with locally advanced gastric cancer treated with surgery alone or in combination with neoadjuvant cisplatin, leucovorin calcium and fluorouracil.
• Compare these two regimens in terms of the rate of complete resection, time to progression, and morbidity in these patients.
• Evaluate toxicity of and disease response to neoadjuvant chemotherapy in these patients.
• Evaluate quality of life and performance status in these patients pre- and post-surgery and compare quality of life for both regimens.

OUTLINE: This is a randomized, open label, multicenter study. Patients are stratified according to center, primary tumor category (cT3 or cT4), localization of tumor (upper third including cardia II or III vs middle and lower third), gender, and histological subtype (intestinal vs nonintestinal). Patients are randomized to one of two treatment arms.

• Patients receive cisplatin IV over 1 hour on days 1, 15, and 29. Patients also receive leucovorin calcium IV over 2 hours followed by fluorouracil IV over 24 hours on days 1, 8, 15, 22, 29, and 36. A second course is administered beginning 2 weeks later in the absence of disease progression or unacceptable toxicity. Patients undergo resection and lymphadenectomy on days 57-63 of the second course of chemotherapy.
• Arm II: Patients undergo resection and lymphadenectomy within 14 days of randomization. Quality of life is assessed before randomization, every 3 months for 1 year and at 2 years after randomization.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, then every 3 months thereafter until death.

PROJECTED ACCRUAL: A total of 360 patients (180 per arm) will be accrued for this study over 4 years.

Ages Eligible for Study:  18 Years   -   69 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically proven stage II-IV adenocarcinoma of the stomach including cardia carcinoma types II and III
• Locally resectable disease
• No distant metastases except M1 lymph nodes
• No evidence of peritoneal carcinomatosis
• Free tumor cells in lavage at laparoscopy allowed
• No uncontrolled bleeding of the primary tumor
• No gastric outlet syndrome or complete tumor stenosis that would require total parenteral nutrition

PATIENT CHARACTERISTICS: Age:

• 18 to 69

Performance status:

• WHO 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 4,000/mm^3
• Absolute neutrophil count greater than 2,000/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.25 times upper limit of normal (ULN)
• Prothrombin rate at least 70%

Renal:

• Creatinine no greater than 1.25 times ULN
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• No prior atrial or ventricular arrhythmias
• No prior congestive heart failure
• No myocardial infarction within the past 6 months

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other prior or concurrent neoplasm except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix
• No active infection
• No allergy to protocol drugs
• No dementia or significantly altered mental status
• No other serious medical condition that would prevent compliance

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No filgrastim (G-CSF) within 48 hours prior to chemotherapy

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• See Disease Characteristics
• No prior stent implantation
• No prior laser therapy

Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium
Egypt
      National Cancer Institute of Egypt, Cairo,  Egypt
Germany
      Department of Medicine III, Erlangen,  D-91054,  Germany
      Evangelisches Bethesda Krankenhaus GmbH, ESSEN,  D-45355,  Germany
      Klinik & Poliklinik fur Strahlentherapie der Universitat zu Koln, Koln,  D-50924,  Germany
      Kliniken Essen - Mitte, ESSEN,  D-45136,  Germany
      Klinikum der J.W. Goethe Universitaet, Frankfurt,  D-60590,  Germany
      Klinikum Rechts Der Isar/Technische Universitaet Muenchen, Munich,  D-81675,  Germany
      Krankenhaus Nordwest, Frankfurt,  D-60488,  Germany
      Kreiskrankenhaus Meissen, Meissen,  D-01657,  Germany
      Medizinische Klinik I, Dresden,  D-01307,  Germany
      Robert Roessle Klinik, Berlin,  D-13122,  Germany
      Staedtisches Krankenhaus, Solingen,  D-42653,  Germany
      Universitaetsklinik Duesseldorf, Duesseldorf,  D-40225,  Germany
      Universitatsklinik - Saarland, Homburg,  D-66421,  Germany
      Westfaelische Wilhelms-Universitaet, Muenster,  DOH-48149,  Germany
Netherlands
      Academisch Ziekenhuis Maastricht, Maastricht,  6202 AZ,  Netherlands
Portugal
      Instituto Portugues de Oncologia Centro do Porto, SA, Porto,  4200,  Portugal

Study chairs or principal investigators

Christoph Schuhmacher,  Klinikum Rechts Der Isar/Technische Universitaet Muenchen   

Study ID Numbers:  CDR0000067315; EORTC-40954
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  December 10, 1999
ClinicalTrials.gov Identifier:  NCT00004099
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08