2-PHASE STUDY OF HEPATIC-ARTERY VASCULAR OCCLUSION WITH MICROENCAPSULATED CISPLATIN IN PATIENTS WITH LIVER METASTASES FROM NEUROENDOCRINE TUMORS

OBJECTIVE. We conducted a two-phase trial in which 100-mu m polylactic acid microcapsules with a cisplatin payload (manufactured at our inst itution [the M. D. Anderson Cancer Center]) were used for hepatic arte ry occlusion therapy for symptomatic patients who had liver metastases from neuroendocrine tumors. SUBJECTS AND METHODS, Between January 199 3 and December 1995, 20 patients with advanced, unresectable, symptoma tic neuroendocrine tumors with liver metastases received repeated hepa tic artery occlusion therapy using encapsulated cisplatin. The dose of encapsulated cisplatin was increased in a stepwise fashion. Selective angiography was used to occlude the portion of the hepatic vasculatur e that had the most metastases with encapsulated cisplatin microcapsul es. In each patient, hepatic artery occlusion therapy was repeated in 6-8 weeks and responses were evaluated. Subsequent vascular occlusions were performed on the basis of the level of palliation achieved and t he persistence of symptoms. RESULTS, Of the 20 patients, 17 patients h ad carcinoid tumors and three had islet cell tumors. The median percen tage of liver replacement was approximately 50%, Fifteen of the 20 pat ients had received prior therapy and 17 patients had hormonal syndrome at the beginning of therapy. One patient had tumor bulk-related sympt oms. Nineteen patients had elevated peptides markers that could be fol lowed serially, Six patients received encapsulated cisplatin at 50 mg/ m(2), four patients at 75 mg/m(2), and 10 patients at 100 mg/m(2) of b ody surface area. The median number of vascular occlusive procedures p er patient was three, All patients were assessable for toxicity and 18 were assessable for response (the other two patients were not assessa ble because of loss of follow-up). The median follow-up lime was 14 mo nths. Twelve (67%) of 18 patients had a median reduction in symptoms o f 50%. Eleven (73%) of 15 patients with elevated 24-hr-urine levels of 5-hydroxyindoleacetic acid had a median reduction of 64% for this sym ptom. We observed objective reduction in the tumors of 14 of the 18 pa tients, In six of the 14 patients, we noted a partial response. In eig ht, we observed a minor response. In four of the is patients, we noted no response. One treatment-related death resulted from hepatorenal sy ndrome. Other major complications included hepatic pain (100%), fever (100%), nausea (100%), and vomiting (95%). Also, all patients had a tr ansient elevation of liver enzymes, Five of the 20 patients died of di sease during our study. CONCLUSION, Hepatic artery vascular occlusion therapy using encapsulated cisplatin is feasible, can palliate symptom s, and can produce biochemical and objective responses in liver metast ases from neuroendocrine tumors. The maximum tolerated dose appears to be 100 mg/m(2) of body surface area per treatment. Polylactic acid ca psules have potential because they can incorporate multiple agents, Wi th surface coating, such capsules can also be used to target specific receptors.