ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2012
Defining the risk of toxicity in phase I oncology trials of novel molecularly targeted agents: a single centre experience.
Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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15 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- The role of age on dose-limiting toxicities in phase I dose-escalation trials.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Pooled it
- Safety, efficacy and survival of patients with primary malignant brain tumours (PMBT) in phase I (Ph1) trials: the 12-year Royal Marsden experience.Journal of neuro-oncology · 2018Trial
- Recruitment, outcomes, and toxicity trends in phase I oncology trials: Six-year experience in a large institution.Cancer reports (Hoboken, N.J.) · 2022Article
- Article
- Cancer drug development: The missing links.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- A study of 1088 consecutive cases of electrolyte abnormalities in oncology phase I trials.European journal of cancer (Oxford, England : 1990) · 2018Article
- Delayed adverse events in phase I trials of molecularly targeted and cytotoxic agents.Oncotarget · 2018Article
- Systems Pharmacology Model of Gastrointestinal Damage Predicts Species Differences and Optimizes Clinical Dosing Schedules.CPT: pharmacometrics & systems pharmacology · 2018Article
- Article
- Dose Titration Algorithm Tuning (DTAT) should supersede 'the' Maximum Tolerated Dose (MTD) in oncology dose-finding trials.F1000Research · 2017Article
- Complications of hyperglycaemia with PI3K-AKT-mTOR inhibitors in patients with advanced solid tumours on Phase I clinical trials.British journal of cancer · 2015Article
- Evaluation of the Safety and Benefit of Phase I Oncology Trials for Patients With Primary CNS Tumors.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015Article
- Higher Risk of Infections with PI3K-AKT-mTOR Pathway Inhibitors in Patients with Advanced Solid Tumors on Phase I Clinical Trials.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- Nomogram to predict cycle-one serious drug-related toxicity in phase I oncology trials.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2014Article
- Creatinine clearance is associated with toxicity from molecularly targeted agents in phase I trials.Oncology · 2012Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThis study defined the risk of serious toxicity in phase I trials of molecularly targeted agents (MTA). PATIENTS AND
methodsA retrospective analysis of toxicity data from patients treated in phase I trials of MTAs was carried out to define the rate of treatment-related grade 3/4 toxic effects, deaths and risk factors associated with grade 3 or more toxicity.
resultsData from 687 patients [median age, 59.1 years (range 12.5-85.5)] treated in 36 trials were analysed. Two hundred and eleven patients were of Eastern Cooperative Oncology Group performance status (PS) zero, 432 of PS one, 38 of PS two and 6 unknown. The rate of grade 3 and 4 events was 14.1% (n=97) and 1.9% (n=13), respectively. Twenty-four percent of events were gastrointestinal, 22% constitutional and 20% metabolic. PS two was associated with a higher risk of toxicity [odds ratio (OR), 2.6; 95% confidence interval (CI) 1.1-6.1; P=0.032] as was receiving >100% of maximum tolerated dose or maximum administered dose (OR 2.5; CI 1.6-3.9; P<0.001). Mortality rate was 0.43% (n=3).
conclusionsTherapy with novel MTAs in phase I trials is associated with a moderate risk of significant toxicity. This appears less than in phase I studies involving cytotoxic agents, particularly in relation to grade 4 toxicity. The risk of death is low.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.