Phase II radiation therapy oncology group trial of weekly paclitaxel and conventional external beam radiation therapy for supratentorial glioblastomamultiforme

Purpose: Fractionated external beam radiotherapy (EBRT) +/- carmustine (BCN U) is the standard of care for patients with glioblastoma multiforme (GBM), but survival results remain poor. Preclinical studies indicate synergy bet ween RT and paclitaxel (TAX) in astrocytoma cell lines. Phase I studies in GBM have demonstrated a maximum tolerated dose for TAX of 225 mg/m(2)/3h/we ek x 6, during EBRT, with no exacerbation of typical RT-induced toxicities. The Radiation Therapy Oncology Group (RTOG) therefore mounted a Phase II s tudy to determine the feasibility and efficacy of conventional EBRT and con current weekly TAX at its MTD. Patients and Methods: Sixty-two patients with histologic diagnosis of GBM w ere enrolled from 8/16/96 through 3/21/97 in a multi-institutional Phase II trial of EBRT and TAX 225 mg/m(2)/3 h (1-3 h before EBRT), administered th e first treatment day of each RT week. Total EBRT dose was 60 Gy (200 cGy/f raction), 5 days per week. A smaller treatment field, to include gross dise ase plus a margin only, was used after 46 Gy. Results: Sixty-one patients (98%) were evaluable. Median age was 55 years ( range, 28-78). Seventy-four percent were greater than or equal to 50 years. Recursive partitioning analysis (RPA) Classes III, IV, V, VI included 10 ( 17%), 21 (34%), 25 (41%), and 5 (8%) patients, respectively. Gross total re section was performed in only 16%. There was no Grade 3 or 4 neutropenia or thrombocytopenia. Hypersensitivity reactions precluding further use of TAX occurred in 4 patients. There were 2 instances of late neurotoxicity (4% G rade 3 or 4). Ninety-one percent of patients received treatment per protoco l. Seventy-seven percent completed prescribed treatment (6 weeks). Of 35 pa tients with measurable disease, CR/PR was observed in 23%, MR in 17%, and S D in 43%. Seventeen percent demonstrated progression at first follow-up. Me dian potential follow-up time is 20 months. Median survival is 9.7 months, with median survivals for RPA classes III, IV, V, and VI of 16.3, 10.2, 9.5 , 2.5 months, respectively. Ten patients remain alive. Conclusion: Concurrent full-dose EBRT and weekly high-dose TAX is feasible in the majority of GBM patients. Acute toxicity is acceptable; myelosuppres sion and peripheral sensory neuropathy are surprisingly modest, despite con siderably higher overall dose intensity, compared to that achievable in oth er disease sites. Median survival by RPA class without prolonged adjuvant t herapy is comparable to RTOG controls treated with standard EBRT and BCNU ( 1 year of BCNU). (C) 2001 Elsevier Science Inc.