PURPOSE: The mammalian target of rapamycin complex 1 (mTORC1) is aberrantly activated in many head and neck squamous cell carcinomas (HNSCCs). This phase I study combines the mTORC1 inhibitor temsirolimus with carboplatin and paclitaxel. METHODS: This was a single institution phase I study for patients with R/M HNSCC with a standard 3 + 3 design. Three doses of temsirolimus were planned: 15, 20, and 25 mg. Due to excessive toxicity with the original study regimen, the protocol was amended to carboplatin AUC 1.5, paclitaxel 80 mg/m(2), and temsirolimus (according to dose escalation plan), all on days 1 and 8 of a 21-day cycle. RESULTS: 18 patients (14 male, 4 female) enrolled, with median age 56 years (range 33-78). The most common toxicities were anemia, leukopenia, thrombocytopenia, and hyperglycemia. Among all patients treated, the confirmed objective partial response (cPR) rate was 22 %. DLT was not exceeded among 6 patients treated at dose level 3 of the revised protocol, and 4 of 6 subjects treated at this dose level had cPRs. CONCLUSION: The phase II recommended regimen is temsirolimus 25 mg, carboplatin AUC 1.5, and paclitaxel 80 mg/m(2), all on days 1 and 8 of a 21-day cycle. A phase II study of this regimen in R/M HNSCC is ongoing.
PURPOSE: The mammalian target of rapamycin complex 1 (mTORC1) is aberrantly activated in many head and neck squamous cell carcinomas (HNSCCs). This phase I study combines the mTORC1 inhibitor temsirolimus with carboplatin and paclitaxel. METHODS: This was a single institution phase I study for patients with R/M HNSCC with a standard 3 + 3 design. Three doses of temsirolimus were planned: 15, 20, and 25 mg. Due to excessive toxicity with the original study regimen, the protocol was amended to carboplatin AUC 1.5, paclitaxel 80 mg/m(2), and temsirolimus (according to dose escalation plan), all on days 1 and 8 of a 21-day cycle. RESULTS: 18 patients (14 male, 4 female) enrolled, with median age 56 years (range 33-78). The most common toxicities were anemia, leukopenia, thrombocytopenia, and hyperglycemia. Among all patients treated, the confirmed objective partial response (cPR) rate was 22 %. DLT was not exceeded among 6 patients treated at dose level 3 of the revised protocol, and 4 of 6 subjects treated at this dose level had cPRs. CONCLUSION: The phase II recommended regimen is temsirolimus 25 mg, carboplatin AUC 1.5, and paclitaxel 80 mg/m(2), all on days 1 and 8 of a 21-day cycle. A phase II study of this regimen in R/M HNSCC is ongoing.
Authors: Leo Mascarenhas; Yueh-Yun Chi; Pooja Hingorani; James R Anderson; Elizabeth R Lyden; David A Rodeberg; Daniel J Indelicato; Simon C Kao; Roshni Dasgupta; Sheri L Spunt; William H Meyer; Douglas S Hawkins Journal: J Clin Oncol Date: 2019-09-12 Impact factor: 44.544
Authors: David M Hyman; Alexandra E Snyder; Richard D Carvajal; John F Gerecitano; Martin H Voss; Alan L Ho; Jason Konner; Jennifer L Winkelmann; Megan A Stasi; Kelsey R Monson; Alexia Iasonos; David R Spriggs; Philip Bialer; Mario E Lacouture; Jerrold B Teitcher; Nora Katabi; Matthew G Fury Journal: Cancer Chemother Pharmacol Date: 2015-02-12 Impact factor: 3.333
Authors: Matthew G Fury; Eric Sherman; Alan L Ho; Han Xiao; Frank Tsai; Oby Nwankwo; Camelia Sima; Adrian Heguy; Nora Katabi; Sofia Haque; David G Pfister Journal: Cancer Date: 2013-02-13 Impact factor: 6.860
Authors: L A Dunn; M G Fury; H Xiao; S S Baxi; E J Sherman; S Korte; C Pfister; S Haque; N Katabi; A L Ho; D G Pfister Journal: Ann Oncol Date: 2017-10-01 Impact factor: 32.976