Dataset Information

Phase 1/2 trials of Temozolomide, Motexafin Gadolinium, and 60-Gy fractionated radiation for newly diagnosed supratentorial glioblastoma multiforme: final results of RTOG 0513.

ABSTRACT: PURPOSE:The purpose of phase 1 was to determine the maximum tolerated dose (MTD) of motexafin gadolinium (MGd) given concurrently with temozolomide (TMZ) and radiation therapy (RT) in patients with newly diagnosed supratentorial glioblastoma multiforme (GBM). Phase 2 determined whether this combination improved overall survival (OS) and progression-free survival (PFS) in GBM recursive partitioning analysis class III to V patients compared to therapies for recently published historical controls. METHODS AND MATERIALS:Dose escalation in phase 1 progressed through 3 cohorts until 2 of 6 patients experienced dose-limiting toxicity or a dose of 5 mg/kg was reached. Once MTD was established, a 1-sided 1-sample log-rank test at significance level of .1 had 85% power to detect a median survival difference (13.69 vs 18.48 months) with 60 deaths over a 12-month accrual period and an additional 18 months of follow-up. OS and PFS were estimated using the Kaplan-Meier method. RESULTS:In phase 1, 24 patients were enrolled. The MTD established was 5 mg/kg, given intravenously 5 days a week for the first 10 RT fractions, then 3 times a week for the duration of RT. The 7 patients enrolled in the third dose level and the 94 enrolled in phase 2 received this dose. Of these 101 patients, 87 were eligible and evaluable. Median survival time was 15.6 months (95% confidence interval [CI]: 12.9-17.6 months), not significantly different from that of the historical control (P=.36). Median PFS was 7.6 months (95% CI: 5.7-9.6 months). One patient (1%) experienced a grade 5 adverse event possibly related to therapy during the concurrent phase, and none experience toxicity during adjuvant TMZ therapy. CONCLUSIONS:Treatment was well tolerated, but median OS did not reach improvement specified by protocol compared to historical control, indicating that the combination of standard RT with TMZ and MGd did not achieve a significant survival advantage.

SUBMITTER: Brachman DG

PROVIDER: S-EPMC4706375 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Phase 1/2 trials of Temozolomide, Motexafin Gadolinium, and 60-Gy fractionated radiation for newly diagnosed supratentorial glioblastoma multiforme: final results of RTOG 0513.

Brachman David G DG Pugh Stephanie L SL Ashby Lynn S LS Thomas Theresa A TA Dunbar Erin M EM Narayan Samir S Robins H Ian HI Bovi Joseph A JA Rockhill Jason K JK Won Minhee M Curran Walter P WP

International journal of radiation oncology, biology, physics 20150401 5

<h4>Purpose</h4>The purpose of phase 1 was to determine the maximum tolerated dose (MTD) of motexafin gadolinium (MGd) given concurrently with temozolomide (TMZ) and radiation therapy (RT) in patients with newly diagnosed supratentorial glioblastoma multiforme (GBM). Phase 2 determined whether this combination improved overall survival (OS) and progression-free survival (PFS) in GBM recursive partitioning analysis class III to V patients compared to therapies for recently published historical co ...[more]

PMID: 25832688

Similar Datasets

Project description:PurposeThis open-label, prospective, multicenter single-arm phase II study combined bevacizumab (BV) with radiation therapy (RT) and temozolomide (TMZ) for the treatment of newly diagnosed glioblastoma (GBM). The objectives were to determine the efficacy of this treatment combination and the associated toxicity.Patients and methodsSeventy patients with newly diagnosed GBM were enrolled between August 2006 and November 2008. Patients received standard RT starting within 3 to 6 weeks after surgery with concurrent administration of daily TMZ and biweekly BV. After completion of RT, patients resumed TMZ for 5 days every 4 weeks and continued biweekly BV. MGMT promoter methylation was assessed on patient tumor tissue. A University of California, Los Angeles/Kaiser Permanente Los Angeles (KPLA) control cohort of newly diagnosed patients treated with first-line RT and TMZ who had mostly received BV at recurrence was derived for comparison.ResultsThe overall survival (OS) and progression-free survival (PFS) were 19.6 and 13.6 months, respectively, compared to 21.1 and 7.6 months in the University of California, Los Angeles/KPLA control cohort, and 14.6 and 6.9 months in the European Organisation for Research and Treatment of Cancer-National Cancer Institute of Canada cohort. Correlation of MGMT promoter methylation and improved OS and PFS was retained in the study group. Comparative subset analysis showed that poor prognosis patients (recursive partitioning analysis class V/VI) may derive an early benefit from the use of first-line BV. Toxicity attributable to RT/TMZ was similar, and additional toxicities were consistent with those reported in other BV trials.ConclusionPatients treated with BV and TMZ during and after RT showed improved PFS without improved OS compared to the University of California, Los Angeles/KPLA control group. Additional studies are warranted to determine if BV administered first-line improves survival compared to BV at recurrence.

Project description:PURPOSE:We report a longitudinal assessment of health-related quality of life (HRQOL) in patients with glioblastoma (GBM) treated on a prospective dose escalation trial of 5-fraction stereotactic radiosurgery (25-40 Gy in 5 fractions) with concurrent and adjuvant temozolomide. METHODS:HRQOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire core-30 (QLQ-C30) general, the EORTC quality of life questionnaire-brain cancer specific module (QLQ-BN20), and the M.D. Anderson Symptom Inventory-Brain Tumor (MDASI-BT). Questionnaires were completed at baseline and at every follow-up visit after completion of radiosurgery. Changes from baseline for 9 predefined HRQOL measures (global quality of life, physical functioning, social functioning, emotional functioning, motor dysfunction, communication deficit, fatigue, insomnia, and future uncertainty) were calculated at every time point. RESULTS:With a median follow-up time of 10.4 months (range, 0.4-52 months), 139 total HRQOL questionnaires were completed by the 30 patients on trial. Compliance with HRQOL assessment was 76% at 12 months. Communication deficit significantly worsened over time, with a decline of 1.7 points per month (P=.008). No significant changes over time were detected in the other 8 scales of our primary analysis, including global quality of life. Although 8 patients (27%) experienced adverse radiation effects (ARE) on this dose escalation trial, it was not associated with a statistically significant decline in any of the primary HRQOL scales. Disease progression was associated with communication deficit, with patients experiencing an average worsening of 13.9 points per month after progression compared with 0.7 points per month before progression (P=.01). CONCLUSION:On this 5-fraction dose escalation protocol for newly diagnosed GBM, overall HRQOL remained stable and appears similar to historical controls of 30 fractions of radiation therapy. Tumor recurrence was associated with worsening communication deficit, and ARE did not correlate with a decline in HRQOL.

Dataset Information

Phase 1/2 trials of Temozolomide, Motexafin Gadolinium, and 60-Gy fractionated radiation for newly diagnosed supratentorial glioblastoma multiforme: final results of RTOG 0513.

Publications

Phase 1/2 trials of Temozolomide, Motexafin Gadolinium, and 60-Gy fractionated radiation for newly diagnosed supratentorial glioblastoma multiforme: final results of RTOG 0513.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure