Summary
The frequency of both neurologic toxicity and therapeutic response due to intra-arterial (IA) chemotherapy is decreased by dose reduction. A method to individualize IA drug dosage is needed to provide each patient with the safest, most effective dose. Most trials of IA chemotherapy for malignant glioma have used body surface area (BSA) to calculate dosage; but brain size and arterial distribution do not correlate well with BSA. Fixed doses of cisplatin and BCNU were used in combination to perform 35 IA infusions in 20 malignant gliomas patients. Doses modified by the number of major intracranial vessels supplied by the infused artery were used in 34 infusions in 19 patients. Patients receiving 150 to 200 mg CP and 300 mg BCNU had an incidence of neurologic deficit of 5.6% if ≥ 3 vessels were supplied by the infused artery compared to 42% for those with only 2 vessels. This crude dose modification maintained efficacy while reducing neurologic toxicity. Further refinement is possible using well established intra-arterial pharmacokinetic principles. Intra-arterial dosing based on volume flow at the site of infusion would yield a more reproducible exposure of the infused capillary bed to a drug than methods currently in use. More consistent drug exposure should reduce toxicity due to over dosing and treatment failure due to under dosing.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Kapp JP, Sanford RA: Neurological deficit after carotid infusion of cisplatin and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) for malignant glioma: An analysis of risk factors. Neurosurgery 19: 779–783, 1986
Shapiro WR, Green S: Reevaluating the efficacy of intraarterial BCNU. J Neurosurg 66: 313–315, 1987
Stewart DJ, Grahovac Z, Benoit B, Addison D, Richard M, Dennery J, Hugenholtz H, Russell N, Peterson E, Maroun J, Vandenberg T, Hopkins H: Intracarotid chemotherapy with a combination of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cisdiaminedichloroplatinum (cisplatin), and 4′-O-demethyl-1-O-(4,6-O-2-thenylidene-b-Dglucopyranosyl)epipodophyllotoxin (VM-26) in the treatment of primary and metastatic brain tumors. Neurosurgery 15: 828–833, 1984
Vance RB, Kapp JP: Supraophthalmic carotid infusion with low dose cisplatin and BCNU for malignant glioma. J Neuro-Oncology 3: 287–290, 1986
Skullerud K: Variations in the size of the human brain: influence of age, sex, body length, body mass index, alcoholism, Alzheimer changes and cerebral atherosclerosis. Acta Neurol Scand Supp 102: 1–90, 1985
Bleyer A: Clinical pharmacology of intrathecal methotrexate. II. An improved dosage regimen derived from agerelated pharmacokinetics. Cancer Treatment Reports 61: 1419–1425, 1977
Balis FM, Poplack DG: Central nervous system pharmacology of antileukemic drugs. The Am J Ped Hem/Onc 11: 74–86, 1989
Kapp JP, Vance R, Parker JL, Smith RR: Limitations of high dose intra-arterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) chemotherapy for malignant gliomas. Neurosurgery 10: 715–719, 1982
Blacklock JB, Wright DC, Dedrick RL, Blasberg RG, Lutz RJ, Doppman JL, Oldfield EH: Drug streaming during intra-arterial chemotherapy. J Neurosurg 64: 284–291, 1986
Lutz RJ, Dedrick RL, Boretos JW, Oldfield EH, Blacklock JB, Doppman JL: Mixing studies during intracarotid artery infusions in an in vitro model. J Neurosurg 64: 277–283, 1986
Saris SC, Shook DR, Blasberg RG, Dedrick RL, Doppman JL, Bankiewicz KS, Blacklock JB, Oldfield EH: Carotid artery mixing with diastole-phased pulsed drug infusion. J Neurosurg 67: 721–725, 1987
Rosa L, Patronas N, Devroom H, Lutz R, Carl J, Fitzgibbon E, Fulham M, Doppman J: Intracarotid BCNU for malignant gliomas: efficacy and CNS toxicity after elimination of drug streaming. AANS 1991 Meeting (Poster Abstract # 1306): 517–518, 1991
Kapp JP: Vascular diversion in chemotherapy of brain tumors. Surg Neurol 25: 33–38, 1986
Bobo H: Brief communications-Intracranial BCNU. Neurosurgery 21: 112, 1987
Ross RL, Kapp HP, Hochberg F, Krull IS, Ding XD, Selavka C: Solvent systems for intracarotid 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) infusion. Neurosurgery 12: 512–514, 1983
Dedrick RL: Arterial drug infusion: Pharmacokinetic problems and pitfalls. J Natl Cancer Inst 80: 84–89, 1988
Djerassi I, Jung SK, Reggev A: Response of astrocytoma to high-dose methotrexate with citrovorum factor rescue. Cancer 55: 2741–2747, 1985
Oldfield EO, Dedrick RL, Yeager RL, Clark C, Devroom HL, Chatterji DC, Doppman JL: Reduced systemic drug exposure by combining intra-arterial chemotherapy with hemoperfusion of regional venous drainage. J Neurosurg 63: 726–732, 1985
Feind CR, Herter F, Markowitz A: Improvements in isolation head perfusion. Am J Surg 106: 777–782, 1963
Hochberg FH, Parker LM, Takvorian T, Canellos GP, Zervas NT: High dose BCNU with autologous bone marrow rescue for recurrent glioblastoma multiforme. J Neurosurg 54: 455–460, 1981
Newton HB, Page MA, Junck L, Greenberg HS: Intraarterial cisplatin for the treatment of malignant gliomas. J Neuro-Onc 7: 39–45, 1989
Author information
Authors and Affiliations
Additional information
Address for offprints: 1151 N. State St., Suite 504, Jackson, MS 39202-2407, USA
Rights and permissions
About this article
Cite this article
Bobo, H., Kapp, J.P. & Vance, R. Effect of intra-arterial cisplatin and 1,3-bis(2chloroethyl)-1-nitrosourea (BCNU) dosage on radiographic response and regional toxicity in malignant glioma patients: proposal of a new method of intra-arterial dosage calculation. J Neuro-Oncol 13, 291–299 (1992). https://doi.org/10.1007/BF00172483
Issue Date:
DOI: https://doi.org/10.1007/BF00172483