Two-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-micron polylactic acid microcapsules with a cisplatin payload (manufactured at our institution [the M. D. Anderson Cancer Center]) were used for hepatic artery occlusion therapy for symptomatic patients who had liver metastases from neuroendocrine tumors. SUBJECTS AND METHODS: Between January 1993 and December 1995, 20 patients with advanced, unresectable, symptomatic neuroendocrine tumors with liver metastases received repeated hepatic 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 vasculature that had the most metastases with encapsulated cisplatin microcapsules. 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 the persistence of symptoms. RESULTS: Of the 20 patients, 17 patients had carcinoid tumors and three had islet cell tumors. The median percentage of liver replacement was approximately 50%. Fifteen of the 20 patients had received prior therapy and 17 patients had hormonal syndrome at the beginning of therapy. One patient had tumor bulk-related symptoms. Nineteen patients had elevated peptides markers that could be followed serially Six patients received encapsulated cisplatin at 50 mg/m2, four patients at 75 mg/m2, and 10 patients at 100 mg/m2 of body surface area. The median number of vascular occlusive procedures per patient was three. All patients were assessable for toxicity and 18 were assessable for response (the other two patients were not assessable because of loss of follow-up). The median follow-up time was 14 months. Twelve (67%) of 18 patients had a median reduction in symptoms of 50%. Eleven (73%) of 15 patients with elevated 24-hr-urine levels of 5-hydroxyindoleacetic acid had a median reduction of 64% for this symptom. We observed objective reduction in the tumors of 14 of the 18 patients. In six of the 14 patients, we noted a partial response. In eight, we observed a minor response. In four of the 18 patients, we noted no response. One treatment-related death resulted from hepatorenal syndrome. Other major complications included hepatic pain (100%), fever (100%), nausea (100%), and vomiting (95%). Also all patients had a transient elevation of liver enzymes. Five of the 20 patients died of disease during our study. CONCLUSION: Hepatic artery vascular occlusion therapy using encapsulated cisplatin is feasible, can palliate symptoms, and can produce biochemical and objective responses in liver metastases from neuroendocrine tumors. The maximum tolerated dose appears to be 100 mg/m2 of body surface area per treatment. Polylactic acid capsules have potential because they can incorporate multiple agents. With surface coating, such capsules can also be used to target specific receptors.

Local infusion of urokinase for the lysis of thrombosis associated with permanent central venous catheters in cancer patients.

We assessed the efficacy of local fibrinolytic therapy in 35 axillary-subclavian vein thromboses (SVT) that occurred in cancer patients with percutaneous central venous catheters (CVC). These catheters were indwelling for a median of 1 month (range, one day to 10 months) before thrombosis developed. Urokinase was administered at a dose of 500 to 2,000 U/kg/h. Complete lysis occurred in 25 of 30 thrombi that were directly infused, after a median of four days. Complete lysis occurred in one of 12 thrombi that could not be directly infused with urokinase and in two of six with associated phlebitis. Eighty-one percent of the thrombi that were symptomatic for less than 1 week before treatment resolved, compared with 56% present for longer than 1 week. Sixteen patients who had complete (12) or partial (four) thrombolysis did not have their CVCs removed. All four patients with partial thrombolysis had recurrent thrombosis at a median of eight days (range, one to 90). Only two patients who had complete thrombolysis had recurrent thrombosis, at 8 and 16 months. Only minor hemorrhagic toxicity was seen.

Small-cell osteosarcoma.

Small-cell osteosarcoma, a subtype of osteogenic sarcoma, consists of sheets of round cells that produce an osteoid matrix. It may be confused with Ewing sarcoma if the osteoid matrix is not included in the biopsy. The distinctive radiographic features of an osteoblastic tumor and a pattern of permeative destruction will confirm the histologic diagnosis or indicate the true nature if tumor osteoid is not included in the histological sections. We add 13 patients to the 32 previously reported in the literature. Fourteen (31%) of the 45 are living and well, though three have been followed for only 2 months (Tables 1 and 2). The treatments have been so varied that a statistically significant evaluation cannot be developed. The radiographic features are not distinctive, but the diagnosis may be suggested when a tumor has osteoblastic features in the metaphysis and extends well down into the shaft with a pattern of permeative destruction. The radiographic features are especially important when limited biopsies reveal only sheets of round cells, thus suggesting Ewing sarcoma. The presence of an osteoid-producing tumor as evidenced by osteoblastic new bone formation will lead to the correct diagnosis.