Lancet 2002; 360: 505-15 (August 17, 2002)

Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial

The International Collaborative Ovarian Neoplasm (ICON) Group*
*Members listed at end of paper
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Correspondence to: ICON Trials, Cancer Division, MRC Clinical Trials Unit, London NW1 2DA, UK (e-mail:icon@ctu.mrc.ac.uk)

Summary

Background

Previously, we have shown that the combination of cyclophosphamide, doxorubicin, and cisplatin (CAP) and single-agent carboplatin produce similar survival and progression-free survival rates in women with ovarian cancer. Subsequently, paclitaxel combined with platinum has become a widely accepted treatment for the disease. We aimed to compare the safety and efficacy of paclitaxel plus carboplatin with a control of either CAP or carboplatin alone.

Methods

Between February, 1995, and October, 1998, we enrolled 2074 patients from 130 centres in eight countries. Women were randomly assigned paclitaxel plus carboplatin or control, the control (CAP or single-agent carboplatin) being chosen by the patient and clinician before randomisation. The primary outcome measure was overall survival. Secondary outcomes were progression-free survival and toxicity. Analysis was by intention to treat.

Findings

With a median follow-up of 51 months, 1265 patients had died, and survival curves showed no evidence of a difference in overall survival between paclitaxel plus carboplatin and control (hazard ratio 0·98, 95% CI 0·87-1·10, p=0·74). The median overall survival was 36·1 months on paclitaxel plus carboplatin and 35·4 months on control (difference 0·7 months, 95% CI -3·6 to 4·7). 1538 patients had progressive disease or died, and again, Kaplan-Meier curves showed no evidence of a difference between the groups (hazard ratio 0·93, 95% CI 0·84-1·03, p=0·16). Median progression-free survival was 17·3 months on paclitaxel plus carboplatin and 16·1 months on control (difference 1·2 months, 95% CI -0·5 to 2·8). Paclitaxel plus carboplatin caused more alopecia, fever, and sensory neuropathy than carboplatin alone, and more sensory neuropathy than CAP. CAP was associated with more fever than paclitaxel plus carboplatin.

Interpretation

Single-agent carboplatin and CAP are as effective as paclitaxel plus carboplatin as first-line treatment for women requiring chemotherapy for ovarian cancer. The favourable toxicity profile of single-agent carboplatin suggests that this drug is a reasonable option as first-line chemotherapy for ovarian cancer.

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Accompanying Editorial, appearing in the same issue of Lancet (Abstract not available on-line)

Commentary

Ovarian cancer chemotherapy: carboplatin as standard

Martin H N Tattersall
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Department of Cancer Medicine, University of Sydney, NSW 2006, Australia (e-mail:mtatt@med.usyd.edu.au)