Phase I study of combination chemotherapy using irinotecan hydrochloride and nedaplatin for advanced or recurrent cervical cancer

OBJECTIVE: We performed a phase I clinical study to evaluate combination chemotherapy with irinotecan hydrochloride (CPT-11) and nedaplatin (CPT-11/nedaplatin) for cervical cancer. METHODS: This study included patients with primary or recurrent cervical cancer. The regimen for CPT-11/nedaplatin therapy consisted of CPT-11 administered 3 times over 2 weeks (days 1, 8 and 15) and nedaplatin infused intravenously as a single dose (day 1). This course was repeated at 4-week intervals. The step 1 doses of the two agents were 50 mg/m(2), respectively. Dose escalation was performed in tandem. Plasma CPT-11, SN-38, total platinum, and filterable platinum levels were measured. RESULTS: In step 3 (CPT-11, 60 mg/m(2); nedaplatin, 60 mg/m(2)), dose-limiting toxicity was observed in 2 of 3 patients. The step 3 doses were regarded as the maximum tolerated doses. The incidences of grade 3/4 adverse events in the first courses (n = 12) [and all courses (n = 45)] were: leukopenia 33% (22%), neutropenia 42% (31%), anemia 17% (20%), nausea 8% (7%), and diarrhea 8% (7%). Following CPT-11 administration, the mean areas under the curve (AUC; ng.h/ml) of SN-38 were 0.11 at 50 mg/m(2) and 0.17 at 60 mg/m(2). Following nedaplatin administration, the mean AUCs (microg x h/ml) of filterable platinum were 6.0 at 50 mg/m(2), and 6.0 at 60 mg/m(2). The response rate was 50% (2 complete responses and 2 partial responses). CONCLUSION: The recommended doses of CPT-11 and nedaplatin for a phase II clinical study were established as 50 and 60 mg/m(2), respectively.