Irinotecan therapy in adults with recurrent or progressive malignant glioma.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Friedman
H S
HS
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. fried003@mc.duke.edu
Petros
W P
WP
Friedman
A H
AH
Schaaf
L J
LJ
Kerby
T
T
Lawyer
J
J
Parry
M
M
Houghton
P J
PJ
Lovell
S
S
Rasheed
K
K
Cloughsey
T
T
Stewart
E S
ES
Colvin
O M
OM
Provenzale
J M
JM
McLendon
R E
RE
Bigner
D D
DD
Cokgor
I
I
Haglund
M
M
Rich
J
J
Ashley
D
D
Malczyn
J
J
Elfring
G L
GL
Miller
L L
LL
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001254:Astrocytoma / Q000097:blood / Q000188:drug therapy; D001932:Brain Neoplasms / Q000097:blood / Q000188:drug therapy*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000097:blood / Q000188:drug therapy; D005910:Glioma / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy*; D009837:Oligodendroglioma / Q000097:blood / Q000188:drug therapy
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin