SynthesisClinical cancer research : an official journal of the American Association for Cancer Research2013
Evaluation of utility of pharmacokinetic studies in phase I trials of two oncology drugs.
Synthesis in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
3 citing papers in PubMed.
- Anti-cancer drug combinations approved by US FDA from 2011 to 2021: main design features of clinical trials and role of pharmacokinetics.Cancer chemotherapy and pharmacology · 2022Review
- Metabolism-related pharmacokinetic drug-drug interactions with tyrosine kinase inhibitors: current understanding, challenges and recommendations.British journal of clinical pharmacology · 2015Review
- Design of phase I combination trials: recommendations of the Clinical Trial Design Task Force of the NCI Investigational Drug Steering Committee.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
purposeThere are many phase I trials of oncology drug combinations, very few of which report clinically significant pharmacokinetic interactions. We hypothesized that the utility of such pharmacokinetic drug-drug interaction (DDI) studies is low in the absence of a mechanistic hypothesis. EXPERIMENTAL
designWe retrospectively reviewed 152 phase I (two drug) combination studies published between 2007 and 2011.
resultsOnly 28 (18%) studies had an implicit or explicit rationale, either inhibition/induction of a drug-metabolizing enzyme or transporter, cosubstrates for the same enzyme or transporter, potential for end-organ toxicity, or protein binding. Only 12 (8%) studies demonstrated a statistically significant DDI, on the basis of change in clearance (or area under the curve) of parent drug and/or active metabolite. There was a strong association between a rationale and a demonstrable drug interaction, as only 2% of studies without a rationale demonstrated a DDI, compared with 32% of studies with a rationale (Fisher exact test; P < 10(-6)).
conclusionDDI studies should not be routinely performed as part of phase I trials of oncology combinations.
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What OpenQuestion holds
Registered trials
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