Phase I study of irinotecan combined with mitomycin-C and 5-fluorouracil for gynecological malignancies: the JGOG study.

BACKGROUND A phase I study to evaluate combined therapy with irinotecan (CPT-11), mitomycin-C (MMC), and 5-fluorouracil (5-FU) was performed in patients with gynecological malignancy, especially non-squamous cell carcinoma of the uterine cervix. MATERIALS AND METHODS Eligibility for the study included patients with previously untreated, chemotherapy-naïve cervical and ovarian carcinoma. CPT-11 and MMC were administered on days 1 and 15 by intravenous infusion, while 5-FU was given on days 3 to 7. This regimen was repeated after 5 weeks. Four escalating dose levels were carried out (CPT-11/MMC: 120/5, 120/6, 150/6, and 150/7 mg/m2; 5-FU 600 mg/m2 fixed). RESULTS Fourteen patients were enrolled in the study. Although all the patients had no previous chemotherapy, three patients had undergone a simple hysterectomy and nine had a radical hysterectomy performed before this chemotherapy. The maximum tolerated dose was not reached by using CPT-11 150 mg/m2, MMC 7 mg/m2, and 5-FU 600 mg/m2 because none of the patients experienced any hematological or non-hematological toxicities of grade 4 during the first cycle. CONCLUSION The recommended doses of this new regimen are CPT-11 150 mg/m2, MMC 7 mg/m2, and 5-Fu 600 mg/m2 which can be well tolerated for gynecological malignancies.