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

Cancer Invest. 2017 Aug 9;35(7):484-489. doi: 10.1080/07357907.2017.1340479. Epub 2017 Jul 10.

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: Cumulative toxicities; Delayed toxicities; Long-term tolerability; Tolerable dose.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects*
  • Bortezomib / administration & dosage*
  • Bortezomib / adverse effects*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Dosage Calculations
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Maximum Tolerated Dose
  • Time Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Bortezomib