BACKGROUND: Dermatologic adverse events (AEs) can be key determinants of overall drug tolerability and of the maximum tolerated and recommended phase 2 doses in phase 1 trials. The authors present the largest dedicated analysis of dermatologic AEs on phase 1 trials to date. METHODS: Data from a prospectively maintained database of patients with solid tumors who were enrolled onto Cancer Therapeutics Evaluation Program (CTEP)-sponsored phase 1 trials of cytotoxic or molecularly targeted agents (MTAs) from 2000 to 2010 were analyzed. Cumulative incidence, site, and type of drug-related dermatologic AEs were described and compared. The timing of worst drug-related dermatologic AEs was summarized. RESULTS: In total, 3517 patients with solid tumors and 6165 unique, drug-related dermatologic AEs were analyzed, including 1545 patients on MTA-only trials, 671 on cytotoxic-only trials, and 1392 on combination MTA and cytotoxic trials. Of 1270 patients who had drug-related dermatologic events, the timing of the worst AE was as follows: 743 (cycle 1), 303 (cycle 2), and 224 (cycle 3 or later). Although the cumulative incidence of grade ≥3 drug-related AEs increased to 2.4% by cycle 6, it was only 1.6% at the end of cycle 1. The cumulative incidence of drug-related AEs was highest in patients who received MTA-only therapy (P < .001) and differed by dose level (P < .001). In patients who received MTA-only therapy, drug-related AEs were most common for combination kinase inhibitor-containing therapy (P < .001). CONCLUSIONS: A substantial proportion of drug-related dermatologic AEs occur after the traditional dose-limiting toxicity monitoring period of phase 1 clinical trials. Future designs should account for late toxicities.
BACKGROUND: Dermatologic adverse events (AEs) can be key determinants of overall drug tolerability and of the maximum tolerated and recommended phase 2 doses in phase 1 trials. The authors present the largest dedicated analysis of dermatologic AEs on phase 1 trials to date. METHODS: Data from a prospectively maintained database of patients with solid tumors who were enrolled onto Cancer Therapeutics Evaluation Program (CTEP)-sponsored phase 1 trials of cytotoxic or molecularly targeted agents (MTAs) from 2000 to 2010 were analyzed. Cumulative incidence, site, and type of drug-related dermatologic AEs were described and compared. The timing of worst drug-related dermatologic AEs was summarized. RESULTS: In total, 3517 patients with solid tumors and 6165 unique, drug-related dermatologic AEs were analyzed, including 1545 patients on MTA-only trials, 671 on cytotoxic-only trials, and 1392 on combination MTA and cytotoxic trials. Of 1270 patients who had drug-related dermatologic events, the timing of the worst AE was as follows: 743 (cycle 1), 303 (cycle 2), and 224 (cycle 3 or later). Although the cumulative incidence of grade ≥3 drug-related AEs increased to 2.4% by cycle 6, it was only 1.6% at the end of cycle 1. The cumulative incidence of drug-related AEs was highest in patients who received MTA-only therapy (P < .001) and differed by dose level (P < .001). In patients who received MTA-only therapy, drug-related AEs were most common for combination kinase inhibitor-containing therapy (P < .001). CONCLUSIONS: A substantial proportion of drug-related dermatologic AEs occur after the traditional dose-limiting toxicity monitoring period of phase 1 clinical trials. Future designs should account for late toxicities.
Authors: David M Hyman; Anne A Eaton; Mrinal M Gounder; Gary L Smith; Erika G Pamer; Martee L Hensley; David R Spriggs; Percy Ivy; Alexia Iasonos Journal: J Clin Oncol Date: 2014-01-13 Impact factor: 44.544
Authors: Sophie Postel-Vinay; Carlos Gomez-Roca; L Rhoda Molife; Bhavesh Anghan; Antonin Levy; Ian Judson; Johann De Bono; Jean-Charles Soria; Stan Kaye; Xavier Paoletti Journal: J Clin Oncol Date: 2011-03-28 Impact factor: 44.544
Authors: A Doussau; R Thiébaut; B Geoerger; P Schöffski; A Floquet; M C Le Deley; S Mathoulin-Pélissier; E Rizzo; P Fumoleau; C Le Tourneau; X Paoletti Journal: Ann Oncol Date: 2014-11-17 Impact factor: 32.976
Authors: Mario E Lacouture; Dirk Schadendorf; Chia-Yu Chu; Martina Uttenreuther-Fischer; Uz Stammberger; Dennis O'Brien; Axel Hauschild Journal: Expert Rev Anticancer Ther Date: 2013-03-18 Impact factor: 4.512
Authors: Sophie Postel-Vinay; Laurence Collette; Xavier Paoletti; Elisa Rizzo; Christophe Massard; David Olmos; Camilla Fowst; Bernard Levy; Pierre Mancini; Denis Lacombe; Percy Ivy; Lesley Seymour; Christophe Le Tourneau; Lillian L Siu; Stan B Kaye; Jaap Verweij; Jean-Charles Soria Journal: Eur J Cancer Date: 2014-05-28 Impact factor: 9.162