Abstract
Background: Conventional phase I algorithms for finding a phase-2 recommended dose (P2RD) based on toxicity alone is problematic because the maximum tolerated dose (MTD) is not necessarily the optimal dose with the most desirable risk- benefit trade-off. Moreover, the increasingly common practice of treating an expansion cohort at a chosen MTD has undesirable consequences that may not be obvious. Patients and methods: We review the phase I-II paradigm and the EffTox design, which utilizes both efficacy and toxicity to choose optimal doses for successive patient cohorts and find the optimal P2RD. We conduct a computer simulation study to compare the performance of the EffTox design with the traditional 3+3 design and the continuous reassessment method. Results: By accounting for the risk-benefit trade-off, the EffTox phase I-II design overcomes the limitations of conventional toxicity-based phase I designs. Numerical simulations show that the EffTox design has higher probabilities of identifying the optimal dose and treats more patients at the optimal dose. Conclusions: Phase I-II designs, such as the EffTox design, provide a coherent and efficient approach to finding the optimal P2RD by explicitly accounting for risk-benefit trade-offs underlying medical decisions.
Original language | English (US) |
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Pages (from-to) | 694-699 |
Number of pages | 6 |
Journal | Annals of Oncology |
Volume | 29 |
Issue number | 3 |
DOIs | |
State | Published - Mar 1 2018 |
Keywords
- Adaptive design
- Dose finding
- Immunotherapy
- Molecularly targeted agents
- Phase I-II trials
- Risk-benefit tradeoff
ASJC Scopus subject areas
- Hematology
- Oncology
MD Anderson CCSG core facilities
- Biostatistics Resource Group