Evaluation of toxicities for intravesical drugs in phase 1 bladder cancer trials
A partir d'une recherche d'essais cliniques de phase I et d'une revue de la littérature (42 études), cette étude analyse la fréquence des toxicités limitant la dose et des événements indésirables graves lors d'instillations intravésicales par rapport à d'autres voies d'administration de médicaments anticancéreux
Background: Improving clinical trial design is important for optimizing approval of safe and effective drugs. Phase 1 clinical trials seek to determine phase 2 doses by investigating predefined dose-limiting toxicities. Traditional definitions of dose-limiting toxicity may not be applicable to intravesical therapies for bladder cancer. This study compared the frequency of dose-limiting toxicities and serious adverse events in bladder cancer trials for intravesical therapies to other routes of administration. Methods: Studies were abstracted from ClinicalTrials.gov and reconciled with a PubMed search. Primary and secondary end points were predefined before data abstraction, and the primary end point was subject–level dose-limiting toxicity rate. Fisher exact tests were performed with p < .05 designated as significant. Results: Eighteen intravesical studies and 24 studies with other routes of administration (the per os/intravenous/intramuscular [PO/IV/IM] group) were identified. Dose-limiting toxicities were reported in 38.9% of intravesical studies, affecting 3.29% of subjects, compared with 30.0% of PO/IV/IM studies representing 4.19% of subjects (p = .52 for study-level and p = .60 for subject-level comparisons). Serious adverse events occurred in 53.9% of intravesical studies in 10.3% of subjects versus 91.0% of studies reporting serious adverse events affecting 41.4% of subjects in the PO/IV/IM group (p = .03 for subject-level and p < .0001 for study-level comparisons). Conclusions: There was no difference in subject–level dose-limiting toxicity rate between intravesical and PO/IV/IM bladder cancer trials. The serious adverse event rate was lower in the intravesical group. Heterogeneity of dose-limiting toxicity definition may affect interpretation of toxicity in phase 1 bladder cancer clinical trials studying different routes of administration.
Cancer 2022