Gemcitabine Plus Radiation Therapy for High-Grade Glioma: Long-Term Results of a Phase 1 Dose-Escalation Study

Journal Article · Mon Feb 01 04:00:00 EST 2016 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/J.IJROBP.2015.10.032· OSTI ID:22645079

Camelo-Piragua, Sandra ^[1]; Schipper, Matthew; Tao, Yebin ^[2]; Normolle, Daniel ^[3]; Junck, Larry; Mammoser, Aaron ^[4]; Betz, Bryan L. ^[1]; Cao, Yue ^[2]; Kim, Christopher J. ^[2]; Heth, Jason; Sagher, Oren ^[5]; Lawrence, Theodore S. ^[2]; Tsien, Christina I. ^[6]

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1. Department of Pathology, University of Michigan, Ann Arbor, Michigan (United States)
2. Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)
3. Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania (United States)
4. Department of Neurology, University of Michigan, Ann Arbor, Michigan (United States)
5. Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan (United States)
6. Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States)

Purpose: To evaluate the tolerability and efficacy of gemcitabine plus radiation therapy (RT) in this phase 1 study of patients with newly diagnosed malignant glioma (HGG). Patients and Methods: Between 2004 and 2012, 29 adults with HGG were enrolled. After any extent of resection, RT (60 Gy over 6 weeks) was given concurrent with escalating doses of weekly gemcitabine. Using a time-to-event continual reassessment method, 5 dose levels were evaluated starting at 500 mg/m{sup 2} during the last 2 weeks of RT and advanced stepwise into earlier weeks. The primary objective was to determine the recommended phase 2 dose of gemcitabine plus RT. Secondary objectives included progression-free survival, overall survival (OS), and long-term toxicity. Results: Median follow-up was 38.1 months (range, 8.9-117.5 months); 24 patients were evaluable for toxicity. After 2005 when standard practice changed, patients with World Health Organization grade 4 tumors were no longer enrolled. Median progression-free survival for 22 patients with grade 3 tumors was 26.0 months (95% confidence interval [CI] 15.6-inestimable), and OS was 48.5 months (95% CI 26.8-inestimable). In 4 IDH mutated, 1p/19q codeleted patients, no failures occurred, with all but 1 alive at time of last follow-up. Seven with IDH mutated, non-codeleted tumors with ATRX loss had intermediate OS of 73.5 months (95% CI 32.8-inestimable). Six nonmutated, non-codeleted patients had a median OS of 26.5 months (95% CI 25.4-inestimable). The recommended phase 2 dose of gemcitabine plus RT was 750 mg/m{sup 2}/wk given the last 4 weeks of RT. Dose reductions were most commonly due to grade 3 neutropenia; no grade 4 or 5 toxicities were seen. Conclusions: Gemcitabine concurrent with RT is well-tolerated and yields promising outcomes, including in patients with adverse molecular features. It is a candidate for further study, particularly for poor-prognosis patient subgroups with HGG.

• OSTI ID: 22645079
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 2 Vol. 94; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
GLIOMAS
GY RANGE 10-100
PATIENTS
RADIATION DOSES
RADIOTHERAPY
TOXICITY