A model to select chemotherapy regimens for phase III trials for extensive-stage small-cell lung cancer

Background: Many more phase ZI studies have favorable outcomes than the sub sequent phase III trials, We used historical data from phase II and phase I II studies for patients with extensive-stage small-cell lung cancer (SCLC) to generate a statistical model to provide assistance in selecting chemothe rapy regimens from phase II studies for subsequent use in phase III randomi zed studies. Methods: Information from 21 phase III trials for patients wit h extensive-stage SCLC initiated during the period from 1972 through 1990 w as reviewed to identify those that were preceded by phase II studies of the same regimen. We used data from all the trial pairs to develop a statistic al model in which the number of patients, the median survival of patients, and the number of deaths observed in the phase II trial are used to estimat e the statistical power of the subsequent phase III trial. All statistical tests were two-sided. Results: Nine phase II studies were identified that p receded phase III trials of the same regimen. The regimens from two phase I I studies with the greatest expected power in the phase III trial (0.62 and 0.58) both demonstrated significantly prolonged survival when compared wit h standard treatment in subsequent phase III trials (P<.001 and P = .002, r espectively). The regimens from six of the other phase LT studies, for whic h the median power expected in the phase III trial was 0.28 (range, 0.19-0. 52), showed no difference when compared with standard treatment in a phase III trial. Conclusions: Phase II studies for particular regimens that have an expected power of greater than 0.55 provide a reasonable basis for proce eding with a phase III trial.