Randomized Phase III Study of Preoperative Chemotherapy Followed by Surgery Versus Surgery Alone in Locally Advanced Gastric Cancer (cT3 and cT4NxM0)

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.

• Arm I: 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.