Defining the risk of toxicity in phase I oncology trials of novel molecularly targeted agents: a single centre experience
Menée sur 687 patients inclus dans 36 essais cliniques de phase I ayant évalué une thérapie ciblée, cette étude analyse le degré de sévérité des effets indésirables associés aux traitements
Background: This study defined the risk of serious toxicity in phase I trials of molecularly targeted agents (MTA).Patients and methods: A 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.Results: Data 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).Conclusions: Therapy 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.
Annals of Oncology , résumé, 2012