Phase I-II study of irinotecan (CPT-11) and nedaplatin (254-S) with recombinant human granulocyte colony stimulating factor support in patients with advanced and recurrent cervical cancer

Abstract

5065 Background: Combination chemotherapy (CT) with CPT-11 and platinum compounds is effective for cervical cancer. 254-S is a new cisplatin analogue that achieves a high response rate (53%) for primary cervical cancer (CC). We performed a phase I-II study of combination CT with CPT-11 and 254-S for advanced or recurrent CC. Methods: Inclusion criteria were stage IV or recurrent disease, bidimensionaly measurarable lesions, PS 0–2, age<75 years, and adequate hematologic, renal, and liver functions. Primary endpoints were toxicity and the response rate. Twenty seven patients (IV=7, recurrence=20) were enrolled with a median age of 54 (32–67) years. CPT-11 and 254-S were administered intravenously on day 1 and rhG-CSF (50μg) was given on days 3–12. This treatment was repeated every 4 weeks for a total of two cycles. Dose escalation was done in tandem. DLTs were defined as G4 hematologic toxicity (HT) or G3 nonhematologic toxicity (NHT). The MTD was reached when the incidence of DLTs exceeded 33.3%. Results: G4 HT occurred in 33%, but there was no G3 NHT. The MTD of CPT-11/254-S were 60/80 mg/m2 and the RD was 50/80 mg/m2 for a phase II study. Response rate (RR) of 68% (95%CI: 49–84%) in phase II study. In 19 patients with disease outside radiation fields and 3 patients with disease inside radiation fields, the RRs were 74% (95%CI: 52–89%) and 33% (95%CI: 10–90%). In 12 responders with recurrent disease, the median time to progression was 161 days (59–711 days). Conclusions: The RD of CPT-11/254-S with rhG-CSF was 50/80 mg/m2, respectively. This is promising for CC. No significant financial relationships to disclose.