Intracarotid Chemotherapy with a Combination of 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU), cis-Diaminedichloroplatinum (Cisplatin), and 4′-O-Demethyl-1-O-(4,6-O-2-thenylidene-β-D-glucopyranosyl)epipodophyllotoxin (VM-26) in the Treatment of Primary and Metastatic Brain Tumors

Abstract

Thirty-seven patients with intracranial primary or metastatic tumors were treated with an intraarterial combination of BCNU, cisplatin, and VM-26 to determine the efficacy, toxicity, and maximal tolerated doses for the combination. A transfemoral fluoroscopic approach was used to catheterize temporarily the internal carotid or vertebral artery. Thirteen of 19 (68%) evaluable primary brain tumors and 9 of 16 (56%) evaluable brain metastases responded. The response rate was lower in patients previously treated with both cranial irradiation and i.v. chemotherapy than in patients less heavily pretreated (54% vs. 82%), although even patients previously treated i.v. with all three of the study drugs responded. All five patients with both extracranial and intracranial evaluable tumor deposits experienced a greater response of their intracranial than of their extracranial tumor. Ipsilateral retinal and neurological toxicity were dose-limiting, with major toxicity (permanent decreased vision or hemiparesis) occurring in five of nine (56%) patients receiving doses of BCNU greater than or equal to 100 mg/m2 plus cisplatin, 60 mg/m2 plus cisplatin, 60 mg/m2, plus VM-26, 175 mg/m2. Only 9% of the patients treated with a lower VM-26 dose developed permanent severe toxicity, and the doses that we now recommend are: BCNU, 100 mg/m2; cisplatin, 60 mg/m2; and VM-26, 150 mg/m2. The response rate was also dose-related (100% at the highest doses tested vs. 57% at the lower doses).(ABSTRACT TRUNCATED AT 250 WORDS)