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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Does maintenance/consolidation chemotherapy have a role in the management of small cell lung cancer (SCLC): a metaanalysis of the published randomized controlled trials

H Bozcuk, M Artac, M Ozdogan, and B Savas.

Review published: 2005.

CRD summary

This review investigated the use of maintenance/consolidation chemotherapy in the management of small-cell lung cancer (SCLC). The authors concluded that maintenance/consolidation chemotherapy improves survival in SCLC, but further large clinical trials are needed to confirm and refine these findings. Given some uncertainty in the review methodology, the authors' cautious conclusions highlighting the need for further research would seem appropriate.

Authors' objectives

To determine the role of maintenance/consolidation chemotherapy in the management of small-cell lung cancer (SCLC).

Searching

MEDLINE and the Cochrane CENTRAL Register were searched for studies published in the English language after 1966; the search terms were provided. References from relevant reviews and textbooks were also checked.

Study selection

Study designs of evaluations included in the review

Randomised controlled trials (RCTs) were eligible for inclusion.

Specific interventions included in the review

Studies that compared a maintenance/consolidation chemotherapy regimen with a no-treatment (follow-up) arm after the completion of induction therapy were eligible for inclusion. Studies had to use 4 to 6 cycles of induction chemotherapy, and a total of more than 6 cycles for the induction and maintenance/consolidation phases combined. Details of the specific chemotherapy regimens used in each study were presented.

Participants included in the review

Studies of patients with SCLC were eligible for inclusion. In the included studies, the stage of disease in patients at randomisation to maintenance treatment was limited disease, extensive disease, or both limited and extensive disease. Required response status prior to maintenance treatment was complete response plus partial response plus stable disease, complete response and partial response, complete response only, or complete response and good response.

Outcomes assessed in the review

The outcomes included in the review were overall survival and progression-free survival. Toxicity was also assessed.

How were decisions on the relevance of primary studies made?

Two medical oncologists independently and then collaboratively reviewed potentially relevant abstracts and selected full-text articles for further review.

Assessment of study quality

The quality of the included trials was assessed using the European Lung Cancer Working Party (ELCWP) score, referring to published ELCWP scores. If the scores had not been published before they were calculated according to published guidelines. The authors did not state how the quality assessment was performed.

Data extraction

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction. Odds ratios (ORs) for 1- and 2-year overall survival and 1- and 2-year progression-free survival were extracted. Where these measures were not directly reported in the primary studies, they were abstracted from reported survival curves. Data on toxicity were also extracted.

Methods of synthesis

How were the studies combined?

The pooled ORs of 1- and 2- year overall survival and progression-free survival were calculated, along with 95% confidence intervals (CIs), using the Mantel-Haenszel test with both fixed-effect and random-effects models. Publication bias was assessed using funnel plots.

How were differences between studies investigated?

Statistical heterogeneity was assessed using chi-squared-based Q tests and was assessed visually in forest plots. Meta-regression analyses were used to investigate differences in effect sizes across studies based on the following prognostic factors: proportion of patients with complete response to induction regimen; proportion of patients with limited disease at the onset of trial; type of induction therapy; type of maintenance/consolidation regimen; year of trial onset; ELCWP scores; and size of trial.

Results of the review

Fourteen RCTs (n=2,550) were included in the review.

There was no indication of publication bias (no further results reported). The ELCWP quality scores ranged from 37 to 85 out of a maximum 102.

Overall survival (14 studies).

Maintenance chemotherapy was associated with a statistically significant improved likelihood of overall survival at both 1 year (OR 0.67, 95% CI: 0.56, 0.79, p<0.001) and 2 years (OR 0.67, 95% CI: 0.53, 0.86, p<0.001) compared with no maintenance therapy, based on a fixed-effect model. Similar results were obtained when using a random-effects model. No statistically significant heterogeneity was detected in either analysis (p=0.186 and p=0.018, respectively).

Progression-free survival (8 studies).

Maintenance chemotherapy was associated with a statistically significant improved likelihood of better progression-free survival at both 1 year (OR 0.49, 95% CI: 0.37, 0.63, p<0.001) and 2 years (OR 0.64, 95% CI: 0.45, 0.92, p=0.015) compared with no maintenance therapy, based on a fixed-effect model. When using a random-effects model, similar results were found for 1-year survival but not for 2-year survival: the results for 2-year survival were no longer statistically significant (OR 0.65, 95% CI: 0.39, 1.09, p=0.099). No statistically significant heterogeneity was detected in either analysis (p=0.210 and p=0.099, respectively).

The results of the meta-regression showed that none of the prognostic factors investigated were significantly associated with any of the outcomes. Where available, data for toxicity were also presented.

Authors' conclusions

Maintenance/consolidation chemotherapy improves survival and should have a role in the management of patients with SCLC. Further large RCTs are needed to confirm and further refine these findings.

CRD commentary

The authors set out a clear objective at the beginning of the review and inclusion criteria were defined. Two relevant databases were searched; however, the search was restricted to English language papers, which increases the risk of language bias, and relevant studies might have been missed. The study selection process was carried out in duplicate, which helps reduce the risk of reviewer error and bias, but it was unclear whether similar methods were used for the quality assessment and data extraction. Study quality appears to have been assessed using appropriate criteria and summary scores were presented. However, it was not clear whether the reviewer authors assessed all studies or whether published scores from previous assessments were used; this might have introduced bias.

Adequate study details were presented. Abstracting event rates from survival curves reported in the primary studies might have introduced error. Although there were some differences between the studies, the statistical pooling seems appropriate: statistical heterogeneity was assessed and known differences between the studies were examined using appropriate techniques. The authors' conclusions accurately reflect the results they presented. Given some uncertainty in the review methodology, the authors' cautious conclusions highlighting the need for further research to confirm their findings would seem appropriate.

Implications of the review for practice and research

Practice: The authors stated that if confirmed, their findings suggest that maintenance/consolidation chemotherapy should play a part in the management of SCLC.

Research: The authors stated that large, well-designed clinical trials are needed to further refine their findings. They stated that studies which stratify patients into prognostic groups and that evaluate different maintenance regimens would help determine which patients should be treated and which treatment regimens should be used.

Funding

Supported in part by Pfizer.

Bibliographic details

Bozcuk H, Artac M, Ozdogan M, Savas B. Does maintenance/consolidation chemotherapy have a role in the management of small cell lung cancer (SCLC): a metaanalysis of the published randomized controlled trials Cancer 2005; 104(12): 2650-2657. [PubMed: 16284984]

Indexing Status

Subject indexing assigned by NLM

MeSH

Adult; Aged; Antineoplastic Combined Chemotherapy Protocols /therapeutic use; Carcinoma, Small Cell /drug therapy /mortality /pathology; Confidence Intervals; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Lung Neoplasms /drug therapy /mortality /pathology; Male; Middle Aged; Neoplasm Staging; Odds Ratio; Patient Selection; Probability; Randomized Controlled Trials as Topic; Risk Assessment; Survival Analysis

AccessionNumber

12006000131

Database entry date

31/10/2007

Record Status

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.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 16284984

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