Phase 2 study of weekly irinotecan in adults with recurrent malignant glioma: final report of NABTT 97-11

Abstract

The primary objective of this study was to determine the proportion of patients exhibiting a radiographic response in a cohort of patients with recurrent malignant glioma who were treated with irinotecan. Secondary objectives were to determine progression-free survival, overall survival, and toxicity. The trial was terminated after the first 18 patients were enrolled in this multicenter, 2-stage, phase 2 study. Twelve patients received concurrent enzyme-inducing antiepileptic drugs, and 6 did not. Each cycle consisted of a 90-min i.v. infusion of irinotecan every week for 4 consecutive weeks, followed by 2 weeks off. One patient had a complete response, 5 patients had stable disease, 5 patients had radiographic progression, 6 patients were removed from the study because of toxicity, and 1 patient refused further therapy and was removed from the study. The response rate in this study was 6% (1/18), and 28% (5/18) of these patients progressed while receiving irinotecan. Dose-limiting toxicities consisted of diarrhea in 5 patients, neutropenia in 1 patient, infection in 1 patient, and respiratory failure in 1 patient. Irinotecan had minimal efficacy in this cohort of 18 patients with recurrent malignant glioma. Toxicity was significant but similar to that reported in other patient populations.

Figures

Fig. 1

Axial (L) and coronal (R) MRI images of the 1 patient who had a complete response. Top Panels. Prechemotherapy, contrast-enhanced, T1-weighted axial and coronal magnetic resonance images demonstrate heterogeneous enhancement of the tumor in the left temporal lobe. Bottom Panels. The enhancement has resolved after CPT-11 therapy, consistent with a complete response.

Fig. 2

Kaplan-Meier curve of overall survival (solid line) and progression-free survival (broken line) of the 18 patients with recurrent glioma.