University of Birmingham Clinical Trials Unit, Park Grange, Birmingham, UK (E-mail: k.wheatley@bham.ac.uk)
In their recent review, Punt and Eggermont [1] state that "combined data from low-dose IFN- [interferon-
] trials does not suggest a benefit in ... DFS [disease-free survival]". This conclusion is inconsistent with the results of a meta-analysis of these trials [2]. It is surprising that Punt and Eggermont [1] do not mention this study, especially as the latter was an author on the meta-analysis. The meta-analysis indicates a significant benefit for IFN-
on DFS: odds ratio (OR) = 0.87, 95% confidence interval (CI) 0.790.96, P = 0.007. The corresponding OR for high-dose trials was 0.76 (95% CI 0.650.89, P = 0.0009). Overall, there is good evidence that IFN-
re-duces recurrence (OR = 0.84, 95% CI 0.770.92, P = 0.0001), but the appropriate test for interaction (P = 0.2) provides no clear evidence that high-dose is more effective than low-dose (Figure 1).
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The use of qualitative scoring systems (i.e. simple + or depending on statistical significance or not) to review treatment efficacy is unsatisfactory and potentially misleading. It is preferable to employ the quantitative methods of systematic meta-analysis. Thus, we agree with Punt and Eggermont that the evidence for a survival benefit with IFN- remains unclear, at all doses, and that a further meta-analysis of all the trials should be undertaken. This should use individual patient data, thereby permitting the inclusion of more mature data, with longer follow-up, than are available in most publications and investigation of whether particular types of melanoma patient benefit from adjuvant IFN-
therapy.
K. Wheatley & N. Ives
University of Birmingham Clinical Trials Unit, Park Grange, Birmingham, UK (E-mail: k.wheatley@bham.ac.uk)
References
1. Punt CJA, Eggermont AMM. Adjuvant interferon- for melanoma revisited: news from old and new studies. Ann Oncol 2001; 12: 16631666.[Abstract]
2. Wheatley K, Hancock B, Gore M et al. Interferon- as adjuvant therapy for melanoma: a meta-analysis of the randomised trials. Proc Am Soc Clin Oncol 2001; 20: 349a (Abstr 1394).
3. Gardner MJ, Altman DG. Confidence intervals rather than P values. In Altman DG, Machin D, Bryant TN, Gardner MJ. Statistics with Confidence, 2nd edition. Bristol: BMJ Books 2000; 1527.
4. Early Breast Cancer Trialists Collaborative Group. Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. Lancet 1992; 339: 115, 7185.[ISI][Medline]
5. Hancock BW, Wheatley K, Harrison G, Gore M. Aim high-adjuvant interferon in melanoma (high risk), a United Kingdom Co-ordinating Committee on Cancer Research (UKCCCR) randomised study of observation versus adjuvant low dose extended duration interferon -2a in high risk resected malignant melanoma. Proc Am Soc Clin Oncol 2001; 20: 349a (Abstr 1393).