Intracarotid Chemotherapy with 1,3-Bis-(2-chloroethyl)-1-nitrosourea (BCNU) in 5% Dextrose in Water in the Treatment of Malignant Glioma

Abstract

After radiotherapy, 20 patients, 18 with documented progression of malignant glioma and 2 with Grade II astrocytoma, received a total of 52 courses of intracarotid 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) at a dose of 150 mg/m2 dissolved in 5% dextrose in water. The patients were treated at 6-week intervals for a maximum of five courses of chemotherapy per patient. Response to treatment was analyzed on computed tomographic scans by measuring the volume of the enhancing tumor and any central low density. From these data, tumor doubling times ranging from 110 to 968 days were obtained. An 11 to 60% reduction in enhancing tumor volume was noted in 8 patients, 2 of whom had a greater than 50% decrease in tumor volume. One patient had no change in tumor volume 110 weeks after the initiation of BCNU chemotherapy. Four patients had tumor in more than one vascular territory; tumor growth was arrested in the perfused territory, but continued in the nonperfused area. In 1 of the 4 patients, tumor also grew along a shunt catheter tract and spread over the surface of the ipsilateral hemisphere. One patient developed clinically asymptomatic leukoencephalopathy after five courses of BCNU. Two patients had postradiation leukoencephalopathy before BCNU treatment. Seventeen patients had peritumoral low density with mass effect after BCNU; thus, the true incidence of BCNU-related leukoencephalopathy could not be determined. All patients experienced transient unilateral orbital pain during the infusion and scleral erythema that lasted for several hours afterward. Loss of vision was noted in 2 patients, although it seemed to be related to the therapy in only 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Osmotic blood-brain barrier disruption and chemotherapy in the treatment of high grade malignant glioma: patient series and literature review

“…In our series two patients suffered a decrease in visual acuity in the eye ipsilateral to the mannitol- [7-10, 13, 24]. Because of the various protocols used at the different centers, it is difficult to make formal comparisons, and it appears that the incidence of visual changes in these series is in keeping with or less than that of intra-carotid therapy in general [3,17,24,25].…”

“…In addition,neuro-oncologists have become concerned with the increasing problem, of postradiation neurotoxicity, either with or without adjuvant chemotherapy. Johnson et al reported their experience with intra-arterial BCNU in 20 patients receiving the drug after 'tumor recurrence' [3]. They contend that patients have less toxicity and survive longer if intra-arterial BCNU is not given immediately after radiation, but is delayed until tumor recurs.…”

Intra-arterial chemotherapy of primary brain tumors

“…Most studies have evaluated a nitrosourea derivative or a platinum analog. Several investigators have evaluated the activity of single-agent IA carmustine [19,20,43,44]. Greenberg et al [19] evaluated the response of 24 patients with recurrent tumors to intracarotid carmustine (200-300 mg/m 2 every 6-8 weeks).…”

Predicted and actual BCNU concentrations in normal rabbit brain during intraarterial and intravenous infusions

“…Clinical studies in the 1980s and 1990s found improved response rates with IA therapy (especially BCNU) in patients with primary and metastatic brain tumors [4][5][6][7][8][9][10][11]. Renewed interest in this form of therapy was based upon the predictions of the theoretical pharmacokinetic modeling.…”