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Maintenance chemotherapy for small cell lung cancer: a critical review of the literature |
Sculier J P, Berghmans T, Castaigne C, Luce S, Sotiriou C, Vermylen P, Paesmans M |
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Authors' objectives To perform a critical review of the effectiveness of maintenance chemotherapy for small cell lung cancer (SCLC).
Searching Current Contents (Life Sciences) was searched for trials published between 1980 and 1996 in English or French. Additional studies were identified by examining the bibliographies of retrieved papers, textbooks and reviews. Trials already known by the authors were also considered.
Study selection Study designs of evaluations included in the reviewRandomised controlled trials (RCTs) evaluating maintenance or consolidation chemotherapy, after an induction regimen for SCLC, as an objective.
Specific interventions included in the reviewFor induction therapy, participants received varying combinations of the following: cyclophosphamide, methotrexate, vincristine, doxorubicin, cisplatin, hexamethylmelamine, ifosfamide, vindesine, and thoracic irradiation. The number of courses varied from 3 to 8. Maintenance chemotherapy was carried out with the same agents as induction in 8 trials, partially with the same agents in 3 trials, and with different agents in 2 trials. The number of courses ranged from 2 to 22, or in one trial, until relapse.
Participants included in the reviewThe participants were people who had received induction chemotherapy for SCLC, who were classified as either complete responders, objective responders, or non-progressing patients at randomisation. In three trials, the participants were allocated to a maintenance regimen at the outset of treatment.
Outcomes assessed in the reviewThe outcomes were survival rates (overall and progression-free), and relationship of trial validity to survival.
How were decisions on the relevance of primary studies made?The authors do not state how the papers were selected for the review, or how many of the authors performed the selection.
Assessment of study quality Internal validity, external validity, protocol design and analysis performance were assessed.Two quality scoring systems were applied, namely those described by Chalmers et al. (see Other Publications of Related Interest) and the European Lung Cancer Working Party (full details provided in the paper). Each trial was independently assessed by seven reviewers. The final scores were arrived at by consensus, during meetings where at least two thirds of the reviewers had to be present. The final scores were converted into percentages.
Data extraction The relationship between quality scores and continuous variables was estimated by correlation. The quality scores were compared with reference to positive versus negative impact on survival, using non-parametric Mann-Whitney tests.
Methods of synthesis How were the studies combined?A narrative overview was conducted.
How were differences between studies investigated?Sensitivity analyses were performed to investigate the relationship between study quality and the reported survival rates.
Results of the review Thirteen RCTs reporting on 2,474 patients were included.
Data on survival rates.
One trial showed a statistically-significant survival advantage with maintenance therapy, whilst another was significantly not in favour. Five trials showed some significant survival advantages in subgroups and/or in multivariate analysis. Progression-free survival was globally significantly improved by maintenance therapy in 4 trials and in subgroups in another. However, it was also unchanged in 4 trials and not assessed in another 4.
Data on quality assessment of trials.
The European Lung Cancer Working Party scores ranged between 37 and 85% (mean 57, standard deviation 14), whilst the Chalmers score ranged from 20 to 77% (mean 46, standard deviation 17). The correlation between both scores was high.
Relationship between survival rates and study quality.
There was no statistically-significant difference in scores between those trials that did, and did not, demonstrate a survival advantage of maintenance therapy. However, a time effect was observed, with earlier trials having lower scores.
Authors' conclusions The trials showing a negative effect of maintenance chemotherapy were not qualitatively better than those showing a positive effect. It can thus be concluded that maintenance therapy can be associated with some survival advantage, as shown by some particular trials. Examples include patients with limited disease where complete response is obtained with cyclophosphamide; cases of objective response after induction with a vincristine-adriamycin- cyclophosphamide regimen and a cisplatin-etoposide regimen; patients where salvage therapy at relapse is not accepted.
CRD commentary This review focused primarily on the methodological aspects of the included trials. The selection criteria for primary studies were clear with regard to study design, but less so for other aspects, namely participants, interventions and outcomes. The quality assessment of the trials was reported in great detail, using text, tables and appendices. However, other details of the primary studies were more sparse. The search strategy was limited to one database and published data only, therefore the possibility of publication bias cannot be excluded. The authors have, appropriately, avoided conducting a meta-analysis due to likely heterogeneity across the trials. The authors' conclusions appeared to be broadly consistent with the findings of the review, although more discussion of the effectiveness of specific chemotherapy regimens within the results section would have been informative.
Implications of the review for practice and research The authors state that 'maintenance chemotherapy could have some indications and good-quality trials, as reflected by very high-quality scores, need to be carried out in the future'.
Bibliographic details Sculier J P, Berghmans T, Castaigne C, Luce S, Sotiriou C, Vermylen P, Paesmans M. Maintenance chemotherapy for small cell lung cancer: a critical review of the literature. Lung Cancer 1998; 19(2): 141-151 Other publications of related interest Chalmers TC, Smith H, Blackburn B, Silverman B, Schroeder B, Reitman D, et al. A method for assessing the quality of a randomized control trial. Control Clin Trials 1981;2:31-49.
Indexing Status Subject indexing assigned by NLM MeSH Antineoplastic Combined Chemotherapy Protocols /therapeutic use; Carcinoma, Small Cell /drug therapy /mortality; Humans; Lung Neoplasms /drug therapy /mortality; Randomized Controlled Trials as Topic; Remission Induction; Survival Rate AccessionNumber 11998000709 Date bibliographic record published 30/09/1999 Date abstract record published 30/09/1999 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. |
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