A phase II study of biweekly mitomycin C and irinotecan combination therapy in patients with fluoropyrimidine-resistant advanced gastric cancer: a report from the Gastrointestinal Oncology Group of the Japan Clinical Oncology Group (JCOG0109-DI Trial)

Background Preclinical studies have shown that mitomycin C (MMC) acts synergistically with irinotecan (CPT-11). In this phase II study, we evaluated the efficacy and toxicity of MMC/CPT-11 therapy as second-line chemotherapy for patients with fluoropyrimidine-resistant advanced gastric cancer. Methods Eligible patients had evidence of tumor progression despite prior treatment with fluoropyrimidine-based regimens or had relapsed within 6 months after completion of therapy with adjuvant fluoropyrimidines. Treatment consisted of MMC (5 mg/m(2)) and CPT-11 (150 mg/m(2)) administered i.v. every 2 weeks. The primary endpoint was the response rate (RR). Our hypothesis was that this combination therapy was efficacious when the lower boundary of the 95% confidence interval (CI) of the RR exceeded 20% of the threshold RR. Results Between April 2002 and July 2003, 45 eligible patients were registered and analyzed. Among the 45 patients, 40 (89%) had previously received chemotherapy for metastasis and 24 (53%) had a performance status (PS) of 0. Thirteen partial responses were obtained among the 45 patients, resulting in an overall RR of 29% (95% CI, 16-42%). The median time to progression was 4.1 months, and the median survival time was 10 months, with a 1-year survival rate of 36%. Grade 4 neutropenia was observed in 29% of the patients, whereas febrile neutropenia occurred in 9%. The incidence rates of grade 3 nausea and diarrhea were 13 and 2%, respectively. Conclusions Although this study did not achieve the per-protocol definition of activity, the progression-free survival and overall survival appeared to be promising, with acceptable tolerability. Thus, MMC/CPT-11 therapy as second-line chemotherapy for fluoropyrimidine-resistant advanced gastric cancer presents a potential treatment option in patients with a good PS.