Clinical trial of CPT-11 and VM-26/VP-16 for patients with recurrent malignant brain tumors.

Author(s): Feun LG, Marini A, Landy H, Markoe A, Heros D, Robles C, Herrera C, Savaraj N

Affiliation(s): Sylvester Comprehensive Cancer Center, University of Miami, and VA Medical Center, Miami, FL 33136, USA. lfeun@med.miami.edu

Publication date & source: 2007-04, J Neurooncol., 82(2):177-81. Epub 2006 Oct 19.

Publication type: Clinical Trial, Phase II

CPT-11 is a potent inhibitor of topoisomerase I and has shown antitumor activity in brain xenografts and in clinical trials in recurrent/progressive malignant glioma. VM-26 and VP-16 are topoisomerase II inhibitors and have also shown activity in phase II trials. We performed a phase II trial of intravenous CPT-11 (125 mg/m2) followed 24 h later by VM-26 (125 mg/m2). VP-16 (125 mg/m2) was later substituted for VM-26 due to drug shortage. For patients on anticonvulsants, the starting dose for all drugs was 150 mg/m2. Drugs were given weekly for 3 weeks followed by 1-week rest. Twenty-five patients were entered into the study. Three patients (12%) had improvement in CAT/MRI brain scans (95% confidence interval 3-31%). Fatigue and myelosuppression, mainly leukopenia, were the main toxicities. This combination of the topoisomerase I inhibitor CPT-11 followed by the topoisomerase II inhibitor, VM-26 or VP-16, has shown modest antitumor activity comparable to that reported for each drug singly. Myelosuppression is the main toxicity when topoisomerase I and II inhibitors are combined together.