Clinical trial of CPT-11 and VM-26/VP-16 for patients with recurrent malignant brain tumors.
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.
Feun
Lynn G
LG
Sylvester Comprehensive Cancer Center, University of Miami, and VA Medical Center, Miami, FL 33136, USA. lfeun@med.miami.edu
Marini
Angela
A
Landy
Howard
H
Markoe
Arnold
A
Heros
Deborah
D
Robles
Carlos
C
Herrera
Cristina
C
Savaraj
Niramol
N
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D000077146:Irinotecan; D008279:Magnetic Resonance Imaging; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D013713:Teniposide / Q000008:administration & dosage; D014057:Tomography, X-Ray Computed
D005047:Etoposide; D000077146:Irinotecan; D013713:Teniposide; D002166:Camptothecin