Treatment > Carmustine · Chemotherapy-Enhancing Agents

Meeting Abstract

Evaluation of safety and tolerance of escalating doses of RSR13 administered with a fixed dose of BCNU every six weeks in patients with recurrent malignant glioma: preliminary data of NABTT 9806 phase I/II clinical trial

Pamela Z New, Stuart A Grossman, Tracy Batchelor, Fred Hochberg, Surasak Phuphanich, Kathryn Carson, Regina Priett

University of Texas Health Science Center, San Antonio, TX; Johns Hopkins Oncology Center, Baltimore, MD; Massachusetts General Hospital, Boston, MA; H. Lee Moffitt Cancer Center, Tampa, FL.

The primary objectives of this study are to evaluate safety and tolerance of escalating doses of RSR13 when administered concomitantly with BCNU in patients with recurrent malignant glioma, to determine a maximum tolerated dose (MTD) of RSR13 when administered with BCNU, and to determine the pharmacokinetic profile of the combination.
In Phase II, the efficacy of the determined MTD will be estimated based on response assessment.
RSR13, a synthetic allosteric modifier of hemoglobin, enhances the diffusion of oxygen from blood to tissue.
By increasing tumor oxygenation, RSR13 may augment the cytotoxic effects of chemotherapy, as shown invitro.
Patients receive BCNU at 200 mg/m-2 intravenously over 60 to 120 minutes, every 6 weeks for a maximum of 6 cycles.
RSR13 is administered over 30 min, 30 min prior to the BCNU infusion.
Supplemental oxygen is administered at 4 Liters/min during and after RSR13 infusion.
Adequate pulmonary function tests must be maintained.
RSR13 dose escalation is planned as follows: 25, 50, 75, 100 mg/kg.
Cohorts of 6 patients were anticipated for each dose level.
MRI scans are obtained prior to each odd cycle.

Results. After each of the first 6 patients, completed at least the first cycle (BCNU + RSR13 25 mg/kg), dose-limiting toxicity (grade 4 neutropenia) was observed in 2 patients.
Therefore, this cohort has been expanded to evaluate a total of 12 patients.
In addition, grade 3 leukopenia occurred in 1 patient and grade 3 thrombocytopenia in 2 patients.
No pulmonary complications have occurred.
Survival ranges from 44 to 227 days.

Conclusions. The expanded first cohort (12 patients receiving BCNU + 25 mg/kg RSR13) will help determine the hematologic toxicity of the combination of BCNU and RSR13.
At the dose level of 25 mg/kg, pulmonary toxicity secondary to the combination of nitrosourea and RSR13 has not been identified.
No other significant side effects have been reported to date.
Although statistically significant accrual has not yet been achieved, 3 patients have surpassed 6 month survival post diagnosis of recurrence.

© Copyright 2002 American Society of Clinical Oncology