Oral anticancer drugs: how limited dosing options and dose reductions may affect outcomes in comparative trials and efficacy in patients.
Historically, cancer medicine has avoided the problem of unequal dosing by comparing maximum-tolerated doses of intravenous regimens with proportionate dose reductions for toxicity. However, in recent years, with the development of numerous oral anticancer agents, dosing options are arbitrarily and increasingly limited by the size of pills. We contend that an underappreciated consequence of pill size is unequal dosing in comparative clinical trials and that this can have an impact on outcomes. We discuss how comparative effectiveness trials can be unbalanced and how the use of doses that are not sustainable might affect outcomes, especially marginal ones. We further argue that because of their poor tolerability and their limited dosing options, which often result in large dose adjustments in response to toxicity, the real-world clinical effectiveness of oral anticancer agents may be diminished and may not emulate results achieved in registration trials.
Vinay Prasad and Tito Fojo, National Cancer Institute, National Institutes of Health, Bethesda, MD; and Paul R. Massey, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. vinayak.prasad@nih.gov.
Vinay
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Prasad
Vinay Prasad and Tito Fojo, National Cancer Institute, National Institutes of Health, Bethesda, MD; and Paul R. Massey, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Paul R
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Massey
Vinay Prasad and Tito Fojo, National Cancer Institute, National Institutes of Health, Bethesda, MD; and Paul R. Massey, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Tito
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Fojo
D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002986:Clinical Trials as Topic / Q000379:methods*; D057186:Comparative Effectiveness Research; D004305:Dose-Response Relationship, Drug; D054796:Drug Dosage Calculations; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D012107:Research Design; D016896:Treatment Outcome
D000970:Antineoplastic Agents