Irinotecan therapy in adults with recurrent or progressive malignant glioma.

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.

Steal-prone coronary anatomy and myocardial ischemia associated with four primary anesthetic agents in humans.

To examine the relationship between myocardial ischemia in patients with steal-prone coronary anatomy and the administration of isoflurane anesthesia, we reviewed coronary angiograms of 955 patients who had participated in a randomized trial of the use of one of four primary anesthetics for coronary artery bypass operations. Steal-prone anatomy was found in 31.8% of patients who had received enflurane; 40.0%, halothane; 32.6%, isoflurane; and 31.7%, sufentanil. Detected by greater than or equal to 0.1 mV ST segment displacement, ischemia during anesthesia occurred in 290 (30.4%) of all patients with no difference in the incidence among the four primary anesthetics (27.5%-32.9%). Patients with steal-prone anatomy did not suffer more ischemia than patients who needed coronary artery bypass surgery but with other varieties of coronary anatomy. In patients with steal-prone coronary anatomy, the incidence of myocardial ischemia by primary anesthetic was 24.0% with enflurane, 34.4% with halothane, 32.1% with isoflurane, and 38.2% with sufentanil. Systolic blood pressure less than 90 mm Hg during anesthesia occurred in 416 (45.6%) patients and was twice as common during administration of volatile anesthetics than during that of sufentanil. Hypotension did not increase ischemia frequency in patients with steal-prone anatomy with use of any of the four primary anesthetics including isoflurane. Ischemia was temporally related to hypotension in only 9 patients (0.9%). In none of the 42 patients who had steal-prone anatomy and hypotension during isoflurane anesthesia was ischemia temporally related to hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)