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

ABSTRACT

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.

KEYWORDS:

• Delayed toxicities
• Long-term tolerability
• Cumulative toxicities
• Tolerable dose

Disclaimer

SWOG is a member of the National Clinical Trials Network supported by the National Cancer Institute (NCI). This manuscript was prepared using a limited access data set obtained from SWOG and does not necessarily reflect the opinions or views of SWOG or the NCI.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Funding

This work was supported by the American Cancer Society (grant number MRSG-13-146-01-CPHPS).