Reference Detail

Ref Type

Journal Article

PMID

(26853339)

Authors

Kim MM, Camelo-Piragua S, Schipper M, Tao Y, Normolle D, Junck L, Mammoser A, Betz BL, Cao Y, Kim CJ, Heth J, Sagher O, Lawrence TS, Tsien CI

Title

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

Journal	Vol	Issue	Date	Pages	Journal Short Title
International journal of radiation oncology, biology, physics	94	2	2016 Feb 01	305-11	Int J Radiat Oncol Biol Phys

URL

Abstract Text

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).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(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.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(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.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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
ATRX loss IDH1 mut	high grade glioma	predicted - sensitive	Gemcitabine + Radiotherapy	Phase I	Actionable	In a Phase I trial, Gemzar (gemcitabine) plus radiation therapy resulted in median overall survival of 73.5 months in 7 high-grade glioma patients with IDH mutated, non-codeleted tumors with ATRX loss (PMID: 26853339).	26853339