Pre-irradiation internal carotid artery BCNU in treatment of glioblastoma multiforme

Restricted access

✓ High-dose 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) infusion into the internal carotid artery following cranial irradiation in the treatment of glioblastoma multiforme is accompanied by evidence of leukoencephalopathy in a significant number of patients. In an attempt to avoid this problem, a phase I trial was performed using intracarotid BCNU infusion before irradiation. Twenty-eight patients with grade III/III astrocytoma (World Health Organization Classification, equivalent to Kernohan grade IV) received a 400-mg infusion of BCNU into the infraophthalmic carotid artery. The treatment was repeated every 4 weeks for a total of four cycles prior to cranial irradiation (5500 to 6000 cGy). The major toxic sequelae included nausea and vomiting (24%), decreased visual acuity (14%), transient cerebral ischemia (3.5%), and thrombocytopenia (3.5%). Fatal leukoencephalopathy occurred in two patients. The median survival time was 37 weeks for all evaluable patients and 56+ weeks for those completing the protocol. The tumor response to drug infusion as judged by computerized tomography (CT) was complete in 22% of patients and partial in 22%; 56% showed no CT tumor response.

Pre-irradiation intracarotid artery BCNU benefits a very small group of patients with grade III/III astrocytoma. The associated severe leukoencephalopathy makes this mode of therapy unacceptable for a phase III trial.

Article Information

Address reprint requests to: Rifaat Bashir, M.D., Brain Tumor Center, Cox Building, Massachusetts General Hospital, 14 Fruit Street, Boston, Massachusetts 02114.

© AANS, except where prohibited by US copyright law.

Headings

References

1.

Balsom BBleyer ARobison Let al: Cranial irradiation in young children: can intellectual deficits be prevented with pretreatment methotrexate? Proc Am Soc Clin Oncol 6:1551987 (Abstract)Proc Am Soc Clin Oncol 6:

2.

Collins JM: Pharmacologic rationale for regional drug delivery. J Clin Oncol 2:4985041984Collins JM: Pharmacologic rationale for regional drug delivery. J Clin Oncol 2:

3.

De Vita VTCarbone PPOwen AH Jret al: Clinical trials with 1,3-bis(2-chloroethyl)-l-nitrosourea, NSC-409962. Cancer Res 25:187618811965Cancer Res 25:

4.

Foo SHChoo ISBerenstein Aet al: Supraophthalmic intracarotid infusion of BCNU for malignant glioma. Neurology 36:143714441986Neurology 36:

5.

Greenberg HSEnsminger WDChandler WFet al: Intra-arterial BCNU chemotherapy for treatment of malignant gliomas of the central nervous system. J Neurosurg 61:4234291984J Neurosurg 61:

6.

Hochberg FHPruitt AABeck DOet al: The rationale and methodology for intra-arterial chemotherapy with BCNU as treatment for glioblastoma. J Neurosurg 63:8768801985J Neurosurg 63:

7.

Layton PBGreenberg HSStetson PLet al: BCNU solubility and toxicity in the treatment of malignant astrocytomas. J Neurosurg 60:113411371984J Neurosurg 60:

8.

Levin VAKabra PMFreeman-Dove MA: Pharmacokinetics of intracarotid artery 14C-BCNU in the squirrel monkey. J Neurosurg 48:587593197814C-BCNU in the squirrel monkey. J Neurosurg 48:

9.

Madajewicz SWest CRPark HCet al: Phase II study — intra-arterial BCNU therapy for metastatic brain tumors. Cancer 47:6536571981Cancer 47:

10.

Rowland JGlidewell OSibley Ret al: Effect of cranial radiation on neuropsychologic function in children with acute lymphocytic leukemia. Proc Am Soc Clin Oncol 1:1231982 (Abstract)Proc Am Soc Clin Oncol 1:

11.

Shapiro WR: Therapy of adult malignant brain tumors: what have the clinical trials taught us? Semin Oncol 13:38451986Shapiro WR: Therapy of adult malignant brain tumors: what have the clinical trials taught us? Semin Oncol 13:

12.

Shapiro WR: Treatment of neuroectodermal brain tumors. Ann Neurol 12:2312371982Shapiro WR: Treatment of neuroectodermal brain tumors. Ann Neurol 12:

13.

Shapiro WRGreen SB: Reevaluating the efficacy of intraarterial BCNU. J Neurosurg 66:3133151987 (Letter)J Neurosurg 66:

14.

Stewart DJBenjamin RSZimmerman Set al: Clinical pharmacology of intraarterial cis-diamminedichloroplatinum(II). Cancer Res 43:9179201983cis-diamminedichloroplatinum(II). Cancer Res 43:

15.

Walker MDStrike TASheline GE: An analysis of dose-effect relationships in the radiotherapy of malignant gliomas. Int J Radiat Oncol Biol Phys 5:172517311979Int J Radiat Oncol Biol Phys 5:

16.

Zülch KJ: Geneva: World Health Organization19794366Zülch KJ:

TrendMD

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 8 8 5
Full Text Views 78 78 22
PDF Downloads 42 42 14
EPUB Downloads 0 0 0

PubMed

Google Scholar