TY - JOUR
T1 - Gemcitabine Plus Radiation Therapy for High-Grade Glioma
T2 - Long-Term Results of a Phase 1 Dose-Escalation Study
AU - Kim, Michelle M.
AU - Camelo-Piragua, Sandra
AU - Schipper, Matthew
AU - Tao, Yebin
AU - Normolle, Daniel
AU - Junck, Larry
AU - Mammoser, Aaron
AU - Betz, Bryan L.
AU - Cao, Yue
AU - Kim, Christopher J.
AU - Heth, Jason
AU - Sagher, Oren
AU - Lawrence, Theodore S.
AU - Tsien, Christina I.
N1 - Funding Information:
This study was partially funded through the University of Michigan Taubman Institute Scholar Grant (T.S.L.), the National Institutes of Health through the University of Michigan Cancer Center Support Grant ( P30 CA046592 ) by the use of the Cancer Center Tissue Core (S.C.-P. and B.L.B.), and the Biostatistics Facility of the University of Pittsburgh Cancer Institute Support Grant ( P30 CA047904 ) (D.N.).
Funding Information:
This study was partially funded through the University of Michigan Taubman Institute Scholar Grant (T.S.L.), the National Institutes of Health through the University of Michigan Cancer Center Support Grant (P30 CA046592) by the use of the Cancer Center Tissue Core (S.C.-P. and B.L.B.), and the Biostatistics Facility of the University of Pittsburgh Cancer Institute Support Grant (P30 CA047904) (D.N.).
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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/m2 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/m2/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.
AB - 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/m2 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/m2/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.
UR - http://www.scopus.com/inward/record.url?scp=84953400742&partnerID=8YFLogxK
U2 - 10.1016/j.ijrobp.2015.10.032
DO - 10.1016/j.ijrobp.2015.10.032
M3 - Article
C2 - 26853339
AN - SCOPUS:84953400742
SN - 0360-3016
VL - 94
SP - 305
EP - 311
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 2
ER -