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

Lynn G. Feun, Angela Marini, Howard Landy, Arnold Markoe, Deborah Heros, Carlos Robles, Cristina Herrera, Niramol Savaraj

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)177-181
Number of pages5
JournalJournal of neuro-oncology
Volume82
Issue number2
DOIs
StatePublished - Apr 2007

Keywords

  • Brain tumor
  • Chemotherapy
  • CPT-11
  • VM-26
  • VP-16

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neuroscience(all)

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