edotecarin and Brain-Neoplasms

Recent clinical trial results suggest that anti-angiogenic therapy may be effective against recurrent malignant glioma. Though these treatments prolong progression-free survival, the extent to which they prolong overall survival is unknown. We pooled data from 34 patients treated at a single institution on phase II clinical trials of bevacizumab and cediranib, and we compared these data to 18 patients treated on clinical trials of cytotoxic chemotherapies. In univariate and multivariate analyses, treatment group was a significant predictor of progression-free but not overall survival. Median progression-free survival was 8 vs. 22 weeks in patients treated with cytotoxic as compared to anti-angiogenic therapy (P = 0.01). Median overall survival was nearly identical in the two groups (39 vs. 37 weeks). The results of this exploratory analysis suggest that anti-angiogenic therapy may fail to prolong overall survival in patients with recurrent malignant glioma. If this conclusion proves correct, progression-free survival may be an inappropriate endpoint for phase II trials of anti-angiogenic therapies.

Topics: Adult; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Brain Neoplasms; Camptothecin; Carbazoles; Clinical Trials as Topic; Disease-Free Survival; Female; Glioma; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Recurrence, Local; Quinazolines; Survival Analysis

We describe the response to a new chemotherapy agent, topoisomerase I inhibitor edotecarin in an 18-year-old woman with recurring glioblastoma. The therapy was administered for 17 months. The radiological partial response and clinical improvement have been achieved, with minor toxicity. Median survival of patients with glioblastoma is 10 months. With edotecarin we have achieved promising result, which should encourage further investigations to develop more efficient therapy for such a deadly disease.

Topics: Adolescent; Antineoplastic Agents; Brain Neoplasms; Carbazoles; Combined Modality Therapy; Female; Glioblastoma; Humans; Indoles; Topoisomerase I Inhibitors

The in vivo antitumor activity of a novel topoisomerase I inhibitor, J-107088, was tested in athymic nude mice bearing subcutaneous or intracranial pediatric and adult malignant CNS tumor-derived xenografts.. J-107088 was administered to animals on days 1-5 and 8-12 via intraperitoneal injection at a dose of 54 mg/kg (162 mg/m2) per day in 10% dimethyl sulfoxide in 0.9% saline. The xenografts evaluated were derived from a childhood glioblastoma multiforme (D-456 MG), a childhood medulloblastoma (D-341 MED), an adult anaplastic astrocytoma (D-54 MG), an adult glioblastoma multiforme (D-245 MG), and a procarbazine-resistant subline of D-245 MG [D-245 MG (PR)].. J-107088 produced regressions and significant growth inhibition in all five of the xenograft lines growing subcutaneously. Growth delays ranged from 7.6 days with D-245 MG to 62.1 days with D-456 MG (P < 0.001). J-107088 also produced an 83% increase in survival in mice bearing intracranial D-456 MG (P < 0.001).. These results indicate that J-107088 may be active in the treatment of childhood and adult malignant brain tumors and provide the rationale for initiation of clinical trials with this agent.

Topics: Adult; Animals; Antineoplastic Agents; Brain Neoplasms; Carbazoles; Child; Enzyme Inhibitors; Female; Glioma; Glucosides; Humans; Indoles; Injections, Intraperitoneal; Injections, Subcutaneous; Male; Mice; Mice, Nude; Neoplasm Transplantation; Survival Rate; Topoisomerase I Inhibitors; Transplantation, Heterologous; Treatment Outcome; Tumor Cells, Cultured