Faculty Collaboration Database

Phase 2 Study of Radiation Therapy Plus Low-Dose Temozolomide Followed by Temozolomide and Irinotecan for Glioblastoma: NRG Oncology RTOG Trial 0420. Int J Radiat Oncol Biol Phys 2019 Mar 15;103(4):878-886

Date

11/30/2018

Pubmed ID

30496882

Pubmed Central ID

PMC7034757

DOI

10.1016/j.ijrobp.2018.11.008

Scopus ID

2-s2.0-85061550338 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

PURPOSE: To evaluate the toxicity and efficacy of adjuvant temozolomide (TMZ) and irinotecan (CPT-11) for 12 months after concurrent chemoradiation in patients with newly diagnosed glioblastoma (GBM).

METHODS AND MATERIALS: Trial RTOG 04-20, a single-arm, multi-institutional phase 2 trial, was designed to determine the efficacy and toxicity of concomitant TMZ and radiation therapy (RT) followed by adjuvant TMZ combined with CPT-11 given for 12 cycles compared with historical controls of adjuvant TMZ alone given for 6 cycles.

RESULTS: A total of 170 patients were enrolled, 152 of whom were eligible. Adjuvant CPT-11 combined with TMZ was more toxic than expected. A higher rate of hematologic and gastrointestinal toxicities was more frequently noted with the combination regimen compared with adjuvant TMZ alone. Grade 3/4 hematologic toxicity was 38% compared with 14% reported in the Stupp trial. After an early interim analysis, the adjuvant CPT-11 dose was reduced to 100 mg/m² on days 1 and 5 for the first cycle. CPT-11 dose escalation proceeded over the first 3 cycles if tolerated. Median overall survival for all eligible patients was 16.9 months compared with 13.7 months of the historical control (P = .03). Post hoc subgroup analysis suggested an improvement in overall survival for patients with Radiation Therapy Oncology Group recursive partitioning analysis class 3, although improvement was limited to 22 patients (14% of eligible patients).

CONCLUSIONS: Although irinotecan and TMZ for 12 cycles given after chemoradiation for patients with newly diagnosed glioblastoma significantly improved median survival compared with historical control data at the time the study was conducted, the historical control median survival time of 13.7 months does not represent the current benchmark for this patient population. Treatment intensification does prolong overall survival compared with the current standard.

Author List

Lieberman FS, Wang M, Robins HI, Tsien CI, Curran WJ Jr, Werner-Wasik M, Smith RP, Schultz C, Hartford AC, Zhang P, Mehta MP

Author

Christopher J. Schultz MD Chair, Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Combined Modality Therapy
Dose-Response Relationship, Drug
Female
Glioblastoma
Humans
Male
Middle Aged
Safety
Survival Analysis
Treatment Outcome
Young Adult