A randomized, phase III trial of paclitaxel plus carboplatin (TC) versus paclitaxel plus cisplatin (TP) in stage IVb, persistent or recurrent cervical cancer: Japan Clinical Oncology Group study (JCOG0505).

Abstract

5006 Background: TC is a less toxic regimen in terms of milder nephropathy, neuropathy and no need of hospitalization. This multicenter phase III trial was designed to evaluate the clinical benefits of TC compared with TP which is current standard chemotherapy for stage IVB or recurrent cervical cancer. Methods: Patients (pts) with stage IVB or recurrent cervical cancer; not amenable to curative therapy; 0-1 prior platinum; no prior taxanes; were randomized with minimization method to either TP (T 135 mg/m2 24h d1 + P 50 mg/m2 2h d2) or TC (T 175 mg/m2 3h d1 + C AUC5 1h d1), both for maximum 6 cycles every 21 days. Primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), toxicities, and the proportion of non-hospitalization periods (NHP) as a surrogate for QoL. The trial was powered at least 70% to confirm the non-inferiority of TC to TP (threshold hazard ratio [HR] 1.29) in terms of OS, and the planned sample size was 250 pts with one-sided alpha 5%. HR is estimated by a stratified Cox regression. Results: From 2/06 to 11/09, 253 pts were enrolled. 71% pts of TP arm and TC arm each received 6 cycles. Median follow-up is 17.4 mo. Results are as below. As an alpha level for an interim analysis was less than 0.0001, significance level for the final analysis is approximately 5% even after the multiplicity adjustment. Conclusions: This first randomized controlled trial comparing carboplatin doublet with cisplatin doublet showed significant non-inferiority of TC in terms of OS. More feasible and less toxic TC can be recommended as the new standard treatment for stage IVB or recurrent cervical cancer. [Table: see text]