PURPOSE: The optimal end point for randomized phase II trials of anticancer 
therapies remains controversial. We simulated phase II trials by resampling 
patients from N9741, a randomized phase III trial of chemotherapy regimens for 
metastatic colorectal cancer, and compared the power of various end points to 
detect the superior therapy (FOLFOX [infusional fluorouracil, leucovorin, and 
oxaliplatin] had longer overall survival than both IROX [irinotecan plus 
oxaliplatin] and IFL [irinotecan and bolus fluorouracil plus leucovorin]).
METHODS: Tumor measurements and progression-free survival (PFS) data were 
obtained for 1,471 patients; 1,002 had consistently measured tumors and were 
resampled (5,000 replicates) to simulate two-arm, randomized phase II trials 
with α = 0.10 (one sided) and 20 to 80 patients per arm. End points included log 
ratio of tumor size at 6, 12, and 18 weeks relative to baseline; time to tumor 
growth (TTG), estimated using a nonlinear mixed-effects model; and PFS. Arms 
were compared using rank sum tests for log ratio and TTG and a log-rank test for 
PFS.
RESULTS: For FOLFOX versus IFL, TTG and PFS had similar power, with both 
exceeding the power of log ratio at 18 weeks; for FOLFOX versus IROX, TTG and 
log ratio at 18 weeks had similar power, with both exceeding the power of PFS. 
The best end points exhibited > 80% power with 60 to 80 patients per arm.
CONCLUSION: TTG is a powerful end point for randomized phase II trials of 
cytotoxic therapies in metastatic colorectal cancer; it was either comparable or 
superior to PFS and log ratio at 18 weeks. Additional studies will be needed to 
clarify the potential of TTG as a phase II end point.