A RANDOMIZED PHASE III TRIAL OF PACLITAXEL PLUS CARBOPLATIN (TC) VERSUS PACLITAXEL PLUS CISPLATIN (TP) IN STAGE IVB OR RECURRENT CERVICAL CANCER: JAPAN CLINICAL ONCOLOGY GROUP STUDY (JCOG0505)

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Abstract

Background

TC is a less toxic regimen in terms of milder nephropathy, neuropathy and no need of hospitalization. This phase III trial was designed to evaluate the clinical benefits of TC compared with TP which is the current standard chemotherapy for stage IVB or recurrent cervical cancer.

Methods

Patients with stage IVB or recurrent cervical cancer—not amenable to curative therapy; 0-1 prior platinum; no prior taxanes—were randomized with the 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 six cycles every 21 days. Primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), toxic effects, and the proportion of non-hospitalization periods (NHP) as a surrogate for QoL. The planned sample size was 250 patients with one-sided α = 5% and at least 70% power to confirm the non-inferiority of TC to TP (threshold hazard ratio [HR] 1.29) in terms of OS. HR is estimated by a stratified Cox regression.

Results

From February 2006 to November 2009, 253 patients were enrolled. The median follow-up is 17.4 months. 71% of patients of the TP arm and TC arm each received six cycles. Results are as follows: as an αlevel for an interim analysis was <0.0001, the significance level for the final analysis is ∼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 of stage IVB or recurrent cervical cancer. TP TCOS (median) 18.3 months, 17.5 months, HR 0.99 (multiplicity adjusted 90% CI: 0.79–1.25); non-inferiority P = 0.032 PFS (median) HR 1.04 (95% CI: 0.80–1.35) 6.90 months 6.21 months neutropenia G3–4 85.1% 76.4% thrombocytopenia G3–4 3.3% 23.6% febrile neutropenia G3–4 16.0% 7.3% creatinine G2–4 9.8% 4.1% neuropathy (motor) G3–4 0.8% 2.4% neuropathy (sensory) G3–4 0% 4.9% NHP (P < 0.0001, Wilcoxon rank sum test) 46.4% 61.9%

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