The review concluded that the maintenance or the consolidation therapy approach failed to improve the outcomes of small-cell lung cancer. A survival advantage was suggested for maintenance chemotherapy and interferon-alpha, but further research is needed. The authors' conclusions were suitably cautious and are likely to be reliable.

To assess the role of maintenance or consolidation therapy in the treatment of small-cell lung cancer.

EMBASE, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) and CANCERLIT were searched up to December 2008. Search terms were reported. Four conference proceedings were scanned.

Randomised controlled trials (RCTs) of maintenance or consolidation therapy versus placebo or follow-up alone in patients with small-cell lung cancer were eligible for inclusion. Consolidation therapy was defined as the administration of the same drug as induction therapy with an a priori duration cut-off point. Maintenance therapy was defined as the administration of additional different drugs at the end of induction therapy with no a priori duration cut-off; maintenance therapy was also used as an all-encompassing term throughout the review. Full definitions were provided in the review.

The primary outcomes were overall survival and progression-free survival. The secondary outcome was compliance.

The included trials studied maintenance/consolidation therapy with chemotherapy, interferons (alpha and gamma), and other biological agents (vandetanib, thalidomide, marimastat, or Bec2/BCG vaccine) compared with control in patients with small-cell lung cancer. The type of induction therapy varied, as did the type of maintenance therapy. Most included patients had extensive disease, but the inclusion of patients who responded completely and those with non-progressive disease varied.

Two reviewers independently performed study selection.

Two reviewers independently assessed trial quality using the Jadad scale, which assessed blinding, randomisation, intention to treat, and allocation concealment. Disagreements between reviewers were resolved by discussion.

Two reviewers extracted data on overall survival and progression-free survival and used the data to calculate hazard ratios (HRs), using Parmar's method, with 95% confidence intervals (CIs). Data on adverse events and compliance were also extracted.

A fixed-effects meta-analysis was undertaken to calculate pooled hazard ratios and 95% confidence intervals. Random-effects meta-analysis was used when significant statistical heterogeneity was detected. Statistical heterogeneity was assessed using the X² and I² statistic.

Subgroup analysis was undertaken by type of drug.

Publication bias was assessed using funnel plots.

Twenty-one trials were included in the review (n=3,687 patients; number cited in figure 1). There were 11 RCTs of chemotherapy, six RCTs of interferons, one RCT of vandetanib, one RCT of thalidomide, one RCT of marimastat, and one RCT of Bec2/BCG vaccine. The included trials were generally poorly reported and may be at risk of bias. Only five trials reported an adequate method of allocation concealment, three reported blinding, and six reported an intention-to-treat analysis.

Total population (all drugs): Compared with control, maintenance therapy did not have a statistically significantly difference in overall survival (HR 0.93, 95% CI 0.87 to 1.00; 3,687 patients) or progression-free survival (HR 0.98, 95% CI 0.91 to 1.06; 2,783 patients). There was substantial heterogeneity in both analyses (I²=60% for overall survival and I²=71% for progression-free survival).

Drug subgroups: Compared with control, maintenance therapy with interferon-gamma or other biological agents did not have a statistically significantly difference for overall survival, but there was a statistically significant benefit in overall survival with maintenance chemotherapy (HR 0.89, 95% CI 0.81 to 0.98; I²=70%; n=1,727 patients) and interferon-alpha (HR 0.78, 95% CI 0.64 to 0.96; I²=0%; n=488 patients). Using a random-effects meta-analysis did not alter the results for interferon-alpha, but the results were no longer significant for chemotherapy (HR 0.87, 95% CI 0.72 to 1.06). Compared with control, the no maintenance therapy drug group had a statistically significantly difference for progression-free survival.

Compliance: The percentage of patients who stopped maintenance therapy due to adverse events was higher with interferons and other biological agents compared with chemotherapy.

There was no evidence of publication bias.

The maintenance or the consolidation approach failed to improve the outcomes of small-cell lung cancer. A survival advantage was suggested for maintenance chemotherapy and interferon-alpha, but the clinical impact needs to be confirmed in further studies.

Inclusion criteria for the review were broadly defined and several relevant data sources were searched. Publication bias was assessed and not detected. Attempts were made to reduce reviewer error and bias throughout the review process.

Quality assessment was undertaken using a standard tool, which indicated that most of the trials were poorly reported and potentially at risk of biases. Trials were pooled using meta-analysis and statistical heterogeneity was assessed. However, the authors were not able to fully explore the sources of heterogeneity due to a lack of data. The authors also stated that the clinical importance of the benefit may be questionable.

Overall, the review had some methodological issues and data problems, but the authors' conclusions were suitably cautious and are likely to be reliable.

Practice: The authors stated that maintenance therapy cannot be considered for routine use in small-cell lung cancer.

Research: The authors stated that further research on maintenance therapy for small-cell lung cancer is needed. They also stated that better selection of drugs for maintenance therapy is needed.

Not stated.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.