ArticleInvestigational new drugs2012
Predictors for establishing recommended phase 2 doses: analysis of 320 dose-seeking oncology phase 1 trials.
Article in Investigational new drugs, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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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.
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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.
- A population pharmacokinetic model of AT9283 in adults and children to predict the maximum tolerated dose in children with leukaemia.British journal of clinical pharmacology · 2017Article
- Dose-finding designs using a novel quasi-continuous endpoint for multiple toxicities.Statistics in medicine · 2013Article
- Tumor control versus adverse events with targeted anticancer therapies.Nature reviews. Clinical oncology · 2011Review
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Authors and funding
7 authors.
Funding
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Abstract
introductionFor decades, determination of the recommended Phase 2 dose (RP2D) was based on the toxicity (especially the maximum tolerated dose or MTD) experienced by patients enrolled in dose-escalating Phase 1 trials investigating anti-cancer agents. Recent studies suggest that this toxicity-based strategy is not suitable for modern anti-cancer agents. We conducted a retrospective study to identify the risk factor(s) for failing to determine the RP2D according to the MTD. MATERIAL AND
methodsWe analyzed 320 recently published (1997-2008) Phase 1 trials using the maximum tolerated dose (MTD) to define the P2RD. We analyzed the current definitions of RP2D and then identified the risk factors for not establishing the RP2D using the odds ratio and 95% confidence intervals. Interactions between these risk factors were explored using the logistic regression model and CHAID algorithm.
results18% of contemporary dose-seeking Phase 1 trials did not identify a RP2D. The logistic regression analysis showed that the risk factors for not identifying the RP2D were: investigation of molecular targeted therapies (RR = 3.0, p = 0.0017), lack of justification of the starting dose (RR = 5.9, p = 0.0121) and lack of definition of the MTD (RR = 8.4, p = 0.0006). The CHAID algorithm confirmed the importance of the methodological parameters. DISCUSSION: This study confirms the difficulty of determining the RP2D of molecular targeted therapy using conventional methods. However, it underlines the major importance of two methodological points: definition of the MTD and justification of the starting dose.
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