The role of a meal on gastrointestinal toxicity and maximum tolerated dose

Unlike bosutinib, phase 1 dose-escalation trials of ceritinib did not account for the effect of a meal on gastrointestinal toxicities and ceritinib pharmacokinetics, raising the concern that the optimum dose for treatment with this drug had not been established.6,7 In the dose-escalation phase, ceri...

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Bibliographic Details
Published in:The lancet oncology 2016, Vol.17 (1), p.e2-e3
Main Authors: Yu, Guo, Wang, Da-Xin, Li, Guo-Fu, Zhou, Hong-Hao
Format: Article
Language:English
Subjects:
Antineoplastic Agents - adverse effects
Clinical trials
Clinical Trials, Phase I as Topic - methods
Cytotoxicity
Diarrhea
Drug dosages
Food
Hematology, Oncology and Palliative Medicine
Humans
Lung cancer
Nausea
Pharmacokinetics
Research Design
Studies
Toxicity
Vomiting
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Summary:Unlike bosutinib, phase 1 dose-escalation trials of ceritinib did not account for the effect of a meal on gastrointestinal toxicities and ceritinib pharmacokinetics, raising the concern that the optimum dose for treatment with this drug had not been established.6,7 In the dose-escalation phase, ceritinib was only given without a meal and the maximum tolerated dose was determined as 750 mg, at which a high frequency of extended grade 1-2 nausea, vomiting, and diarrhoea were reported.8 750 mg dose to patients under fasted conditions was then chosen to be the recommended dose for phase 1 expansion.9 Although 750 mg dose of ceritinib taken without food is highly active in the indicated patients, an unresolved dosing issue raised by the US Food and Drug Administration (FDA) reviewers was the high occurrence of gastrointestinal toxicities (eg, diarrhoea [86%], nausea [80%], and vomiting [60%]), at this dose when administered without food, leading to dose...
ISSN:1470-2045
1474-5488
DOI:10.1016/S1470-2045(15)00552-5