Journal of Clinical Oncology, Vol 10, 484-498, Copyright © 1992 by American Society of Clinical Oncology
Single-agent chemotherapy trials in small-cell lung cancer, 1970 to 1990: the case for studies in previously treated patients
SC Grant, RJ Gralla, MG Kris, J Orazem and EA Kitsis
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
PURPOSE: This review was undertaken (1) to determine the antitumor activity
of agents studied in phase II trials in small-cell lung cancer (SCLC)
patients, (2) to evaluate the adequacy of published trials, (3) to
determine if previously treated patients are suitable for phase II trials
in SCLC, and (4) to develop an improved design for phase II trials. DESIGN:
English-language, single-agent efficacy trials in SCLC, published from 1970
to 1990, were reviewed. Study design and reporting of results were assessed
for clinical and statistical methodology. Response rates observed in
previously treated patients were compared with those observed in previously
untreated patients. RESULTS: One hundred forty-one articles evaluating 57
agents in 3,042 patients were reviewed. Eleven drugs were active (defined
as a response rate greater than or equal to 20% in a trial with greater
than or equal to 14 assessable patients), and 12 were inactive. Due to
methodologic problems with the clinical trials, the usefulness of the
remaining 34 drugs (60%) remains uncertain. Deficiencies identified in
trials include inappropriate sample sizes, poorly defined response
criteria, and failure to report important prognostic factors. When studied
in adequate trials, all agents known to be active in SCLC had an observed
response rate greater than or equal to 10% in previously treated patients.
CONCLUSIONS: Over the past 2 decades, phase II trials in SCLC have failed
in their primary task of effectively identifying agents that warrant
further clinical study and rejecting inactive agents. If only previously
treated patients had been entered into these trials, no useful agent would
have been missed provided that a lower observed response rate had been used
as evidence of antitumor activity. We propose a two-stage sequential study
design, entering previously treated patients, for future phase II trials in
SCLC.
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