At-32a Phase I Dose-escalation Study of Gemcitabine Plus Standard Radiation Therapy for Malignant High Grade Gliomas
Year: 2014
Type: conference-abstract
Abstract: BACKGROUND: Based on preclinical data that gemcitabine (GEM) is an effective radiosensitizer in a mouse glioma model, a phase I study was undertaken assessing the feasibility of administering GEM during radiation therapy (RT) in patients with newly-diagnosed high-grade gliomas. METHODS: Adult patients with pathologically confirmed WHO grade III-IV supratentorial gliomas were eligible. Five dose levels of weekly GEM were tested starting the last 2 weeks of RT and advancing stepwise into earlier weeks (500 mg/m2 weeks 5,6; 1000 mg/m2 weeks 5,6; 1000 mg/m2 weeks 4,5,6; 750 mg/m2 weeks 3,4,5,6 and 1000 mg/m2 weeks 3,4,5,6). All patients received 60 Gy in 30 fractions. Primary objective was to determine the maximum tolerated dose (MTD) associated with DLT (any ≥grade 4 hematologic or ≥grade 3 non-hematologic toxicity) in 20% of patients within 90 days from start RT. Secondary objectives included estimates of ≥grade 3 toxicity, progression-free (PFS) and overall survival (OS). RESULTS: Between 2004-2012, 29 patients were enrolled (6 oligodendroglioma, 10 oligoastrocytoma, 9 astrocytoma and 4 glioblastoma), with 24 evaluable for toxicity. With median follow-up of 35.7 months (IQR, 36.6-58.6), OS for 22 evaluable patients with grade III tumors was 48.0 months (95% CI 26.2-inestimable), and PFS was 26.0 months (95% CI 11.7-48.5). MTD was 750 mg/m2/week given the last 4 weeks of RT. DLT events (grade 3 nausea, venous thromboembolism and syncope at dose levels 3-5) occurred in 4 patients, and three patients had biopsy-confirmed radiation necrosis (1 at dose level 1, 2 at dose level 5). No grade 5 toxicities related to therapy were observed. CONCLUSIONS: Among patients with high-grade gliomas, the MTD of GEM delivered with 60 Gy in 30 fractions was 750 mg/m2/week given the last 4 weeks of RT in this study. The combination of GEM and RT was well-tolerated, and preliminary estimates of efficacy are promising.
Source: Neuro-Oncology
Institution: University of Michigan
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2332548327