TY - JOUR
T1 - RTOG 0913
T2 - A phase 1 study of daily everolimus (RAD001) in combination with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma
AU - Chinnaiyan, Prakash
AU - Won, Minhee
AU - Wen, Patrick Y.
AU - Rojiani, Amyn M.
AU - Wendland, Merideth
AU - Dipetrillo, Thomas A.
AU - Corn, Benjamin W.
AU - Mehta, Minesh P.
N1 - Funding Information:
Conflicts of interest: Dr Chinnaiyan received a research grant from Merck . Dr Wen received a grant and performed consulting/received an honorarium from Merck Novartis, Genentech, and Vascular Biogenics. Dr Dipetrillo performed consultancy for Source Product Equipment Co. Dr Mehta received a consulting fee/honorarium from Roche , Bristol-Meyers Squibb, Abbott, Elekta, Novelos, Novocure, Viewray, and Merck and performed consultancy for Roche, Merck, and the Pharmacyclics Board of Directors (also a Board member).
Funding Information:
This trial was conducted by the Radiation Therapy Oncology Group and was supported by Radiation Therapy Oncology Group grant U10 CA21661 , Community Clinical Oncology Program grant U10 CA37422 from the National Cancer Institute, and Novartis Pharmaceuticals . This manuscript's contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.
PY - 2013/8/1
Y1 - 2013/8/1
N2 - Purpose: To determine the safety of the mammalian target of rapamycin inhibitor everolimus (RAD001) administered daily with concurrent radiation and temozolomide in newly diagnosed glioblastoma patients. Methods and Materials: Everolimus was administered daily with concurrent radiation (60 Gy in 30 fractions) and temozolomide (75 mg/m2 per day). Everolimus was escalated from 2.5 mg/d (dose level 1) to 5 mg/d (dose level 2) to 10 mg/d (dose level 3). Adjuvant temozolomide was delivered at 150 to 200 mg/m2 on days 1 to 5, every 28 days, for up to 12 cycles, with concurrent everolimus at the previously established daily dose of 10 mg/d. Dose escalation continued if a dose level produced dose-limiting toxicities (DLTs) in fewer than 3 of the first 6 evaluable patients. Results: Between October 28, 2010, and July 2, 2012, the Radiation Therapy Oncology Group 0913 protocol initially registered a total of 35 patients, with 25 patients successfully meeting enrollment criteria receiving the drug and evaluable for toxicity. Everolimus was successfully escalated to the predetermined maximum tolerated dose of 10 mg/d. Two of the first 6 eligible patients had a DLT at each dose level. DLTs included gait disturbance, febrile neutropenia, rash, fatigue, thrombocytopenia, hypoxia, ear pain, headache, and mucositis. Other common toxicities were grade 1 or 2 hypercholesterolemia and hypertriglyceridemia. At the time of analysis, there was 1 death reported, which was attributed to tumor progression. Conclusions: Daily oral everolimus (10 mg) combined with both concurrent radiation and temozolomide followed by adjuvant temozolomide is well tolerated, with an acceptable toxicity profile. A randomized phase 2 clinical trial with mandatory correlative biomarker analysis is currently under way, designed to both determine the efficacy of this regimen and identify molecular determinants of response.
AB - Purpose: To determine the safety of the mammalian target of rapamycin inhibitor everolimus (RAD001) administered daily with concurrent radiation and temozolomide in newly diagnosed glioblastoma patients. Methods and Materials: Everolimus was administered daily with concurrent radiation (60 Gy in 30 fractions) and temozolomide (75 mg/m2 per day). Everolimus was escalated from 2.5 mg/d (dose level 1) to 5 mg/d (dose level 2) to 10 mg/d (dose level 3). Adjuvant temozolomide was delivered at 150 to 200 mg/m2 on days 1 to 5, every 28 days, for up to 12 cycles, with concurrent everolimus at the previously established daily dose of 10 mg/d. Dose escalation continued if a dose level produced dose-limiting toxicities (DLTs) in fewer than 3 of the first 6 evaluable patients. Results: Between October 28, 2010, and July 2, 2012, the Radiation Therapy Oncology Group 0913 protocol initially registered a total of 35 patients, with 25 patients successfully meeting enrollment criteria receiving the drug and evaluable for toxicity. Everolimus was successfully escalated to the predetermined maximum tolerated dose of 10 mg/d. Two of the first 6 eligible patients had a DLT at each dose level. DLTs included gait disturbance, febrile neutropenia, rash, fatigue, thrombocytopenia, hypoxia, ear pain, headache, and mucositis. Other common toxicities were grade 1 or 2 hypercholesterolemia and hypertriglyceridemia. At the time of analysis, there was 1 death reported, which was attributed to tumor progression. Conclusions: Daily oral everolimus (10 mg) combined with both concurrent radiation and temozolomide followed by adjuvant temozolomide is well tolerated, with an acceptable toxicity profile. A randomized phase 2 clinical trial with mandatory correlative biomarker analysis is currently under way, designed to both determine the efficacy of this regimen and identify molecular determinants of response.
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U2 - 10.1016/j.ijrobp.2013.04.036
DO - 10.1016/j.ijrobp.2013.04.036
M3 - Article
C2 - 23725999
AN - SCOPUS:84880045561
SN - 0360-3016
VL - 86
SP - 880
EP - 884
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 5
ER -
