Phase I study of combination therapy with irinotecan, leucovorin, and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for advanced colorectal cancer in Japanese patients.

BACKGROUND Irinotecan, leucovorin, and bolus and continuous-infusion 5-fluorouracil administered every two weeks (FOLFIRI regimen) is active in patients with metastatic colorectal cancer. However, the efficacy and toxicity of this regimen in Japanese patients with metastatic colorectal cancer remain unknown. PATIENTS AND METHODS We investigated the maximum tolerated dose, dose-limiting toxicity, and recommended dose at Step 1. Twenty-one patients with metastatic colorectal cancer were enrolled in Step 1. At the five dose levels, fixed doses of bolus 5-fluorouracil (400 mg/m(2)) and leucovorin (200 mg/m(2)) were administered in combination with escalating doses of irinotecan from 120-180 mg/m(2) with 46-h continuous infusion of 5-fluorouracil 2000-3000 mg/m(2) every two weeks. In Step 2, an additional 24 patients received the recommended doses determined in Step 1, and safety and antitumor efficacy were evaluated in terms of tumor response. RESULTS No dose-limiting toxicities were observed at dose levels 1-4. Four out of eight patients experienced a dose-limiting toxicity at level 5; therefore, this level was considered the maximum tolerated dose. Consequently, the recommended doses were determined to be 180 mg/m(2) of irinotecan and 2,400 mg/m(2) of 5-fluorouracil in continuous i.v. infusion. At this level (FOLFIRI-180), National Cancer Institute common terminology criteria grade 3-4 neutropenia, leukopenia, and vomiting were common but manageable. Other hematological and non-hematological toxicities were mild. Seven out of 23 response-assessable patients achieved an objective response (response rate=30%). CONCLUSION This FOLFIRI-180 regimen is manageable and effective in Japanese patients with metastatic colorectal cancer.