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.


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.


CONCLUSIONS
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.
Kokawa
Katsuji
K
Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama, Japan.
Umesaki
Naohiko
N
Yamamoto
Kaichiro
K
Takizawa
Ken
K
Konishi
Ikuo
I
Hasegawa
Kazuo
K
D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy; D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D000077146:Irinotecan; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
D016685:Mitomycin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin