A model to select chemotherapy regimens for phase III trials for extensive-stage small-cell lung cancer.
BACKGROUND
Many more phase II studies have favorable outcomes than the subsequent phase III trials. We used historical data from phase II and phase III studies for patients with extensive-stage small-cell lung cancer (SCLC) to generate a statistical model to provide assistance in selecting chemotherapy regimens from phase II studies for subsequent use in phase III randomized studies.


METHODS
Information from 21 phase III trials for patients with extensive-stage SCLC initiated during the period from 1972 through 1990 was 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 statistical 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 estimate the statistical power of the subsequent phase III trial. All statistical tests were two-sided.


RESULTS
Nine phase II studies were identified that preceded phase III trials of the same regimen. The regimens from two phase II studies with the greatest expected power in the phase III trial (0. 62 and 0.58) both demonstrated significantly prolonged survival when compared with standard treatment in subsequent phase III trials (P<. 001 and P =.002, respectively). The regimens from six of the other phase II studies, for which 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 proceeding with a phase III trial.
Chen
T T
TT
Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA. tchen001@umaryland.edu
Chute
J P
JP
Feigal
E
E
Johnson
B E
BE
Simon
R
R
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic / Q000379:methods; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D004334:Drug Administration Schedule; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015233:Models, Statistical; D009367:Neoplasm Staging; D016032:Randomized Controlled Trials as Topic / Q000379:methods*
D000970:Antineoplastic Agents