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Chemotherapy Compared With Biochemotherapy for the Treatment of Metastatic Melanoma: A Meta-Analysis of 18 Trials Involving 2,621 Patients

Natalie J. Ives, Rebecca L. Stowe, Paul Lorigan, Keith Wheatley

From the Birmingham Clinical Trials Unit, Division of Medical Sciences, Robert Aitken Institute, University of Birmingham, Edgbaston, Birmingham; and the CRUK Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, United Kingdom

Address reprint requests to Natalie Ives, MSc, Birmingham Clinical Trials Unit, Division of Medical Sciences, Robert Aitken Institute, University of Birmingham, Edgbaston, Birmingham B15 2TT; e-mail: n.j.ives{at}bham.ac.uk

Purpose To assess the effect of adding interferon- (IFN) ± interleukin-2 (IL-2) to chemotherapy in patients with metastatic melanoma.

Methods A published data meta-analysis of trials of biochemotherapy versus chemotherapy in patients with metastatic melanoma was undertaken. End points evaluated were rates of partial response (PR), complete response (CR) and overall (partial + complete) response (OR); response duration; progression-free survival; overall survival (OS); and toxicity. The only subgroup analysis performed was by type of immunotherapy, with trials divided according to whether IFN only or IFN and IL-2 were administered in the biochemotherapy arm.

Results Eighteen randomized trials were identified: 11 trials of chemotherapy ± IFN and seven trials of chemotherapy ± IFN and IL-2. More than 2,600 patients were entered onto the trials, with 555 responses and 2,039 deaths. There was a clear benefit for biochemotherapy for PR (odds ratio = 0.66; 95% CI, 0.53 to 0.82; P = .0001), CR (odds ratio = 0.50; 95% CI, 0.35 to 0.73; P = .0003) and OR (odds ratio = 0.59; 95% CI, 0.49 to 0.72; P < .00001). For OR, these benefits were significant for both the IFN (odds ratio = 0.60; 95% CI, 0.46 to 0.79; P = .0002) and IFN + IL-2 (odds ratio = 0.58; 95% CI, 0.44 to 0.77; P = .0001) subgroups. In contrast, there was no benefit overall in OS (odds ratio = 0.99; 95% CI, 0.91 to 1.08; P = .9), but there was evidence of heterogeneity of treatment effect between the individual trials (P = .006).

Conclusion This meta-analysis provides a comprehensive summary of all the data currently available, and shows that although biochemotherapy clearly improves response rates, this does not appear to translate into a survival benefit.

Supported by the National Co-ordinating Centre for Research Capacity Development.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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