Single-agent DTIC versus combination chemotherapy with or without immunotherapy in metastatic melanoma: a meta-analysis of 3273 patients from 20 randomized trials
M. Huncharek et al., Single-agent DTIC versus combination chemotherapy with or without immunotherapy in metastatic melanoma: a meta-analysis of 3273 patients from 20 randomized trials, MELANOMA RE, 11(1), 2001, pp. 75-81
It is currently unclear whether any combination therapy for the treatment o
f metastatic melanoma is superior to standard single-agent dacarbazine (DTI
C) in terms of tumour response and overall survival. The available randomiz
ed clinical trial data were combined in a meta-analysis to address this que
stion. Initially a thorough MEDLARS search was conducted covering the time
period from January 1970 to January 1999. This literature search was supple
mented by manual searches of study bibliographies (including review article
s) and review of relevant textbooks. The meta-analysis was performed accord
ing to a prospective protocol using strict study eligibility criteria. Data
derived from randomized controlled trials comparing single-agent DTIC with
combination chemo/immunotherapy were combined using a fixed effects model.
Data were stratified into three combination therapy groups: DTIC-containin
g regimens, non-DTIC-containing therapy, and chemotherapy plus immunotherap
y. The primary outcome of interest was the proportion of patients demonstra
ting a complete or partial response to treatment. A total of 20 randomized
trials comprising 3273 patients were initially combined in a meta-analysis.
This yielded an odds ratio (OR) of 1.23 (95% confidence interval [CI] 1.02
-1.48), demonstrating that combination drug therapies are associated with a
23% increase in response rate compared with single-agent DTIC. The combina
tion of DTIC plus interferon-a produced a tumour response rate 53% greater
(95% CI 1.10-2.13) than that seen with DTIC alone. This increase was greate
r than that seen with DTIC-containing multi-drug regimens, which had an OR
of 1.33 (95% CI 0.99-1.78). No difference in overall survival was demonstra
ted. Non-DTIC-containing treatment programmes showed no advantage over DTIC
in terms of tumour response rate (OR = 0.77, 95% CI 0.45-1.32). The combin
ation of DTIC and interferon-a appears more active than standard single-age
nt DTIC in metastatic melanoma. Further randomized clinical trials employin
g a DTIC plus interferon arm are necessary to confirm these results. (C) 20
01 Lippincott Williams & Wilkins.