Chemotherapy compared with biochemotherapy for the treatment of metastatic melanoma: a meta-analysis of 18 trials involving 2,621 patients.
OBJECTIVE
To assess the effect of adding interferon-alpha (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).


CONCLUSIONS
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.
Birmingham Clinical Trials Unit, Division of Medical Sciences, Robert Aitken Institute, University of Birmingham, Edgbaston, Birmingham, United Kingdom. n.j.ives@bham.ac.uk
Natalie J
NJ
Ives
Rebecca L
RL
Stowe
Paul
P
Lorigan
Keith
K
Wheatley
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage*; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic
D000970:Antineoplastic Agents; D016898:Interferon-alpha; D007376:Interleukin-2