title: Hypofractionated intensity modulated radiotherapy with temozolomide in newly diagnosed glioblastoma multiforme.
abstract: We conducted a phase I study to determine (a) the maximum tolerated dose of peri-radiation therapy temozolomide (TMZ) and (b) the safety of a selected hypofractionated intensity modulated radiation therapy (HIMRT) regimen in glioblastoma multiforme (GBM) patients. Patients with histological diagnosis of GBM, Karnofsky performance status (KPS)≥ 60 and adequate bone marrow function were eligible for the study. All patients received peri-radiation TMZ; 1 week before the beginning of radiation therapy (RT), 1 week after RT and for 3 weeks during RT. Standard 75 mg/m(2)/day dose was administered to all patients 1 week post-RT. Dose escalation was commenced at level I: 50mg/m(2)/day, level II: 65 mg/m(2)/day and level III: 75 mg/m(2)/day for 4 weeks. HIMRT was delivered at 52.5 Gy in 15 fractions to the contrast enhancing lesion (or surgical cavity) plus the surrounding edema plus a 2 cm margin. Six men and three women with a median age of 67 years (range, 44-81) and a median KPS of 80 (range, 80-90) were enrolled. Three patients were accrued at each TMZ dose level. Median follow-up was 10 months (range, 1-15). Median progression free survival was 3.9 months (95% confidence interval [CI]: 0.9-7.4; range, 0.9-9.9 months) and the overall survival 12.7 months (95% CI: 2.5-17.6; range, 2.5-20.7 months). Time spent in a KPS ≥ 70 was 8.1 months (95% CI: 2.4-15.6; range, 2.4-16 months). No instance of irreversible grade 3 or higher acute toxicity was noted. HIMRT at 52.5 Gy in 15 fractions with peri-RT TMZ at a maximum tolerated dose of 75 mg/m(2)/day for 5 weeks is well tolerated and is able to abate treatment time for these patients.
authors.affiliation: Dardinger Microneurosurgical Skull Base Laboratory, Department of Neurological Surgery, Ohio State University Medical Center, N1025 Doan Hall, 410 W. 10th Avenue, Columbus, OH 43210, USA. Electronic address: Mario.Ammirati@osumc.edu.
authors.forename: Mario
authors.initials: M
authors.lastname: Ammirati
authors.affiliation: Dardinger Microneurosurgical Skull Base Laboratory, Department of Neurological Surgery, Ohio State University Medical Center, N1025 Doan Hall, 410 W. 10th Avenue, Columbus, OH 43210, USA.
authors.forename: Silky
authors.initials: S
authors.lastname: Chotai
authors.affiliation: Department of Neurology, Ohio State University, Columbus, OH, USA.
authors.forename: Herbert
authors.initials: H
authors.lastname: Newton
authors.affiliation: Dardinger Microneurosurgical Skull Base Laboratory, Department of Neurological Surgery, Ohio State University Medical Center, N1025 Doan Hall, 410 W. 10th Avenue, Columbus, OH 43210, USA.
authors.forename: Tariq
authors.initials: T
authors.lastname: Lamki
authors.affiliation: Center for Biostatistics, Ohio State University, Columbus, OH, USA.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Radiation Oncology, Ohio State University, Columbus, OH, USA.
authors.forename: John
authors.initials: J
authors.lastname: Grecula
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D024221:Antineoplastic Protocols; D001932:Brain Neoplasms / Q000628:therapy*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods*; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Concurrent; Glioblastoma multiforme; Hypofractionated; Temozolomide