An exciting prospect in the delivery of chemotherapy is the intra-arterial route. The advantages include directly perfusing the tumor with the drug, thereby not losing efficacy to the firstpass effect. Also, when cisplatin is used, sodium thiosulfate can be given systemically to neutralize the cisplatin by covalently binding to it once it has passed out of the tumor vascular bed. This should allow decreased side effects, including mucositis and nephrotoxicity. The additional risks revolve around the arterial puncture and possible vascular and cerebrovascular events.
Robbins et al.78 evaluated a cohort of 57 patients with stage III (27%) and stage IV (73%) squamous cell carcinoma of the head and neck in a noncontrolled study. These investigators achieved a 75% complete response (CR) rate in the primary tumor and regional neck disease. The treatment includes a femoral artery puncture with arteriography to select the feeding blood vessels to the tumor before administration of the "supradose" cisplatin (150 mg/m2). This is repeated weekly for a total of four doses. The thiosulfate is given intravenously concomitant with the cisplatin. Radiation is delivered using 1.8- to 2.0-Gy fractions daily. Their follow-up time is short, averaging 18 months, but the results are impressive. They report a 91% CR rate of the primary tumor. Fifty-two percent of their patients are alive with no evidence of disease, 25% have died with disease, and 17% died of other causes.
The main argument against intra-arterial chemotherapy is the increase in complication rates without a significant benefit in survival rates. With the addition of the neutralizing agent, the severe grade 3 and 4 mucositis has decreased, as well as nephrotoxicity. Two transient ischemic attacks and two cere-brovascular attacks were reported, with no permanent disability. One patient had deep venous thrombosis, and three patients had pulmonary embolisms, one of whom died.
The results of this trial are encouraging. Only 4% of patients showed a recurrence above the clavicles; 23% failed with distant metastases. Although some complications were serious, the relatively low morbidity of this procedure appears to be highly dependent on the skill of the interventional radiologists, and this may be a limiting factor. In addition, longer survival and disease-free rates need to be reported. The protocol has been expanded to a multi-institutional trial, an important step in ver-ifing the reproducibility of the Memphis trial experience.
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