[Combination chemotherapy with nedaplatin, bleomycin and ifosfamide for advanced cervical cancer of the uterus--a preliminary study for phase III clinical study].

A preliminary co-operative study by 7 institutes was conducted to determine the optimal dosage of the combination regimen with nedaplatin, bleomycin and ifosfamide, which is used in a phase III clinical study, to investigate its efficacy as neoadjuvant chemotherapy against advanced cervical cancer of the uterus. The drug administration consisted of 3 step; in the first step, nedaplatin and bleomycin were administered in a single dose at 80 mg/m2 and a 6-day dose at 7.5 mg/body/day, respectively, and this combination treatment was repeated every 4 weeks. After confirming the safety and efficacy of this combination regimen, the second-step treatment was started in which a 5-day dose of ifosfamide at 600 mg/m2/day was added to the combination regimen of the first step. In the third step, this three-drug combination regimen was used with the daily dose of ifosfamide increased up to 1,200 mg/m2. The drug administration was conducted in a total of 16 cases, consisting of 3 cases in the first step, 7 in the second step and 6 in the third step, which were all evaluable for tumor response and safety. Regarding tumor response, a 33.3% (1/3) of response rate was obtained in the first step, 71.4% (5/7) in the second step and 66.7% (4/6) in the third step. As for safety, bone marrow suppression indicated by grade 4 abnormal clinical laboratory test values was found in one case each in the second step (leukopenia and thrombocytopenia) and the third step (leukopenia). Thus, bone marrow suppression, mainly leukopenia and thro mbocytopenia, was regarded as the dose limiting factor of this three-drug combination regimen. The leucocyte and thrombocyte counts reached their nadirs at two weeks after administration with recovery in about two weeks. The other abnormal changes in clinical laboratory test values such as those indicating the effects on renal function were slight even in the third step. Nausea and vomiting, anorexia and fever were found in every step with high incidences. Alopecia was found in all cases of the third step. Based on the above results, the dosage of the third step (combination regimen with a single dose of nedaplatin at 80 mg/m2, 6-day dose of bleomycin at 7.5 mg/body/day and 5-day dose of ifosfamide at 1,200 mg/m2/day, repeated every 4 weeks) was considered to be the optimal dosage in the phase III clinical study for advanced cervical cancer of the uterus.