Combination Chemotherapy in Treating Patients With Advanced Stomach Cancer

OBJECTIVES:

• Compare the efficacy and tolerability of docetaxel, cisplatin, and fluorouracil (TCF) versus docetaxel and cisplatin (TC) versus epirubicin, cisplatin, and fluorouracil (ECF) in patients with advanced gastric carcinoma.
• Compare the time to treatment failure, time to progression, and survival in this patient population treated with these regimens.
• Compare the quality of life during the treatment period and after failure in this patient population.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center, performance status (0 vs 1), and liver involvement (yes vs no). Patients are randomized to one of three treatment arms.

• Arm I: Patients receive epirubicin IV bolus and cisplatin IV over 4 hours on day 1 plus fluorouracil IV continuously on days 1-21.
• Arm II: Patients receive docetaxel IV over 1 hour and cisplatin IV over 4 hours on day 1.
• Arm III: Patients receive docetaxel and cisplatin as in arm II and fluorouracil as in arm I.

Treatment regimen is repeated every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed before randomization; at day 1 of courses 2, 4, and 6; and one month after treatment failure.

Patients with complete response or partial response are followed monthly for 3 months.

PROJECTED ACCRUAL: Approximately 111 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed gastric carcinoma not amenable to curative surgery or in relapse after primary surgical resection

• Locally advanced disease (i.e., measurable locoregional lymph nodes) OR
• Metastatic disease
• Bidimensionally measurable disease

• At least 10 mm X 20 mm by chest x-ray or physical examination
• At least 10 mm X 10 mm by CT scan
• No CNS metastasis

PATIENT CHARACTERISTICS:

Age:

• 18 to 70

Performance status:

• 0-1

Life expectancy:

• Greater than 12 weeks

Hematopoietic:

• WBC count at least 4,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.25 times upper limit of normal (ULN)
• AST/ALT no greater than 2.5 times ULN
• Alkaline phosphatase no greater than 5 times ULN

Renal:

• BUN normal
• Creatinine normal
• Creatinine clearance at least 60 mL/min
• No severe hypercalcemia

Cardiovascular:

• No unstable cardiac disease requiring treatment
• No congestive heart failure
• No angina pectoris even if medically controlled
• No significant arrhythmias
• No prior myocardial infarction unless ejection fraction at least 50% by MUGA scan or echocardiogram

Neurologic:

• No prior significant neurologic or psychiatric disorders, including psychotic disorders, dementia or seizures that would preclude study
• No peripheral neuropathy of any origin (alcohol, etc.) greater than grade 1

Other:

• Fertile patients must use adequate contraception
• No prior malignancy except basal cell skin cancer or adequately treated carcinoma in situ of the cervix
• No active uncontrolled infection
• No other serious illness or medical condition that would preclude study participation
• No contraindication to corticosteroid use

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior palliative chemotherapy
• At least 12 months since prior adjuvant or neoadjuvant chemotherapy
• No prior taxanes
• Prior fluorouracil allowed in bolus form only
• Prior cumulative dose of adjuvant or neoadjuvant cisplatin no greater than 300 mg/m2

Endocrine therapy:

• Prior or concurrent prednisone (or equivalent) allowed for prophylaxis, acute hypersensitivity reactions, or chronic therapy (greater than 6 months) at doses no greater than 20 mg

Radiotherapy:

• Not specified

Surgery:

• See Disease Characteristics

Other:

• No other concurrent experimental drugs
• No other concurrent anticancer therapies
• At least 30 days since treatment in prior clinical trial