Using Delayed Toxicities to Re-evaluate Tolerability in Phase 2 Trials: A Case Example using Bortezomib.

In advanced stage patients enrolled in dose-finding trials, it is difficult to assess delayed toxicities because frequently patients discontinue after one or two cycles of treatment. Patients enrolled in phase 2 trials are typically followed longer to assess efficacy. Thus, their data may be useful for evaluating long-term tolerability. We illustrate this using as example two phase 2 bortezomib trials (total N = 172) conducted by SWOG. While treatment-related severe toxicity rates based on cycle 1 were acceptable (23% and 31%), they were notably higher over extended administration (37% and 70%). This additional information should be considered when designing subsequent trials.