Irinotecan therapy in adults with recurrent or progressive malignant glioma.

Abstract

PURPOSE:

To determine the activity, toxicity, and pharmacokinetics of irinotecan (CPT-11, Camptosar; Pharmacia & Upjohn, Kalamazoo, MI) in the treatment of adults with progressive, persistent, or recurrent malignant glioma.

PATIENTS AND METHODS:

Patients with progressive or recurrent malignant gliomas were enrolled onto this study between October 1996 and August 1997. CPT-11 was given as a 90-minute intravenous (i.v.) infusion at a dose of 125 mg/m2 once weekly for 4 weeks followed by a 2-week rest, which comprised one course. Plasma concentrations of CPT-11 and its metabolites, SN-38 and SN-38 glucuronide (SN-38G), were determined in a subset of patients.

RESULTS:

All 60 patients who enrolled (36 males and 24 females) were treated with CPT-11 and all were assessable for toxicity, response, and survival. Pharmacokinetic data were available in 32 patients. Nine patients (15%; 95% confidence interval, 6% to 24%) had a confirmed partial response, and 33 patients (55%) achieved stable disease lasting more than two courses (12 weeks). Toxicity observed during the study was limited to infrequent neutropenia, nausea, vomiting, and diarrhea. CPT-11, SN-38, and SN-38G area under the plasma concentration-time curves through infinite time values in these patients were approximately 40%, 25%, and 25%, respectively, of those determined previously in patients with metastatic colorectal cancer not receiving antiepileptics or chronic dexamethasone treatment.

CONCLUSION:

Response results document that CPT-11, given with a standard starting dose and treatment schedule, has activity in patients with recurrent malignant glioma. However, the low incidence of severe toxicity and low plasma concentrations of CPT-11 and SN-38 achieved in this patient population suggest that concurrent treatment with anticonvulsants and dexamethasone enhances drug clearance.

• Authors: H S Friedman, W P Petros, A H Friedman, L J Schaaf, T Kerby, J Lawyer, M Parry, P J Houghton, S Lovell, K Rasheed, T Cloughsey, E S Stewart, O M Colvin, J M Provenzale, R E McLendon, D D Bigner, I Cokgor, M Haglund, J Rich, D Ashley, J Malczyn, G L Elfring, L L Miller
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 17 Issue 5 Pg. 1516-25 (May 1999) ISSN: 0732-183X [Print] United States
• PMID: 10334539 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Irinotecan
• Camptothecin

Topics

• Adult
• Aged
• Antineoplastic Agents, Phytogenic (pharmacokinetics, therapeutic use)
• Astrocytoma (blood, drug therapy)
• Brain Neoplasms (blood, drug therapy)
• Camptothecin (analogs & derivatives, pharmacokinetics, therapeutic use)
• Disease Progression
• Female
• Glioblastoma (blood, drug therapy)
• Glioma (blood, drug therapy)
• Humans
• Irinotecan
• Male
• Middle Aged
• Neoplasm Recurrence, Local (blood, drug therapy)
• Oligodendroglioma (blood, drug therapy)