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

Author： Feun Lynn Marini Angela Landy Howard Markoe Arnold Heros Deborah Robles Carlos Herrera Cristina Savaraj Niramol

ISSN： 0167-594X

Source： Journal of Neuro-Oncology, Vol.82, Iss.2, 2007-04, pp. : 177-181

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Abstract

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.