A Pilot Clinical and Pharmacokinetic Study of Intracarotid Cisplatin and Bleomycin

Abstract

Fifteen patients with progressive primary malignant or metastatic brain tumors were treated on a clinical and pharmacokinetic study with intracarotid cisplatin and bleomycin. Toxicity was tolerable and consisted mainly of nausea and vomiting. Neurologic toxicity included focal seizures (1), leukoencephalopathy (1), and motor weakness (1). Five patients had improvement in CT scans and four patients had stabilization of disease. Recommended dosage for future clinical trials are cisplatin 60 mg/m2 and bleomycin 100 units. Pharmacokinetics of intracarotid cisplatin revealed the jugular vein concentration was twice the peripheral vein level at the end of infusion. Cisplatin is a drug which has demonstrated in vitro activity against malignant gliomas (1). Clinical trials with intravenous administration of cisplatin has shown definite, although limited antitumor activity against primary brain tumors (2,3,4) and metastatic brain tumors (5,6). To enhance its antitumor effect, cisplatin has been administered by the intracarotid route (7,8,9). The results appear encouraging, but neurological and ophthalmological toxicity may occur (8). In our initial study with intracarotid cisplatin, 35 patients with malignant brain tumors (23 with primary brain tumors and 12 with brain metastases) progressing after cranial irradiation +/- chemotherapy were treated. Of 20 evaluable patients with primary tumors, 6 responded to therapy and 5 had stable disease. Five of 10 evaluable patients with brain metastases responded and 2 had stable disease. For responding primary brain tumor patients the median time to progression was 33 weeks. The recommended dose for intracarotid cisplatin was 60-75 mg/m2 administered every 3-4 weeks (7,8). Higher cisplatin doses produced more central neurological toxicity. There is limited data on the central nervous system pharmacology of cisplatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Intraarterial Chemotherapy for Brain Tumors by Using a Spatial Dose Fractionation Algorithm and Pulsatile Delivery

“…Previous reports of intraarterial chemotherapy have described a wide range of complications depending on the infusion protocol, agent used, and catheterrelated technique (10,12,14,15,21,31,32).…”

Intra-arterial cisplatin in malignant brain tumors: incidence and severity of otic toxicity

“…Several trials combining BCNU and IA CDDP have been reported with survival times ranging from 8 weeks to 48 months for responders [17][18][19][20][21]. CDDP intraarterially has also been associated with bleomycin [22], BCNU and VM-26 [23], and etoposide [24]. The response rate in these trials ranged from 28% to 82% with survival times from 33 to 160 weeks.…”

Improving the delivery of therapeutic agents to CNS neoplasms: a clinical review

“…The CNS toxicity and lack of efficacy associated with the intra-carotid delivery of nitrosoureas in phase II studies (12) lead to the evaluation of less lipophilic though "active" agents or combinations of agents (carboplatin, cisplatin, bleomycin , etoposide, TNF-alpha) delivered by the intra-carotid route for the treatment of malignant glioma (13)(14)(15)(16)(17).…”