Phase II study of sequential high-dose methotrexate and fluorouracil combined with doxorubicin as a neoadjuvant chemotherapy for scirrhous gastric cancer

Background. The prognosis of scirrhous gastric cancer remains poor when it is treated with surgical resection alone or chemotherapy alone. A phase II study of sequential high-dose methotrexate and fluorouracil, combined with doxorubicin, as a neoadjuvant chemotherapy was conducted in an attempt to evaluate the efficacy of this regimen in improving the survival of patients with scirrhous gastric cancer. Methods. Patients were eligible if they had potentially resectable scirrhous gastric cancer with adequate organ functions and no prior treatment. The treatment schedule consisted of methotrexate (1 g/m², day 1) fluorouracil (1.5 g/m², day 1), leucovorin (15 mg/m², days 2–4), and doxorubicin (30 mg/m², day 15), repeated at a 28-day interval, and followed by radical surgery. Results. A total of 20 eligible patients were registered. Objective responses in the neoadjuvant chemotherapy segment were observed in 3 of the 20 (15%) patients. No complete remission was observed. The neoadjuvant chemotherapy was associated with grade 3 or 4 neutropenia in 14 of the 20 (70%) patients. The median time from the initial therapy to the operative day was 82 days. Thirteen of the 20 (65%) patients underwent curative resection. No treatment-related deaths occurred. However, the 2-year survival rate in this treatment program (25%) did not show any superiority over that in historical controls. Conclusions. Sequential high-dose methotrexate and fluorouracil, combined, with doxorubicin, as a neoadjuvant chemotherapy for scirrhous gastric cancer did not improve the survival rate in spite of improving the curative resection rate. Received: August 2, 2001 / Accepted: September 27, 2001