A phase II trial of streptozotocin and adriamycin in advanced APUD tumors.

Thirty-three patients with advanced carcinoid tumors, islet cell carcinomas, or medullary carcinomas of the thyroid were entered into a phase II trial combining streptozotocin (STZ) and Adriamycin. Thirty-one patients are evaluable for response, and 29 are evaluable for survival. Six (19%) patients achieved objective partial responses (95% confidence limits: 5.4-33). The median duration of response for partial responders was 282 days. The median survival for responders and nonresponders was 16.2 months and 7.8 months, respectively, with an overall median survival of 10.9 months. At 10.9 months median follow-up, 4 (14%) of 29 patients are surviving. Toxicity was mild, except that nausea or vomiting occurred in 25 of 31 patients evaluable for toxicity. With this dose and schedule of administration, STZ and Adriamycin produce modest response rates with objective palliation of disease in patients with advanced amine precursor uptake and decarboxylation (APUD) tumors.

[Ultrastructural phenotypes of tumor cells of endocrine-cellular neoplasms of hepatopancreatoduodenal organs and their role in determining the degree of malignancy and prognosis of these diseases]. / Ul'trastrukturnye fenotipy opukholevykh kletok éndokrinno-kletochnykh novoobrazovanii organov gepatopankreatoduodenal'noi zony i ikh znachenie v opredelenii stepeni zlokachestvennosti i prognoza étikh zabolevanii.

78 tumors of the hepatopancreoduodenal system were studied clinically, cytologically and ultrastructurally. Hormonal disturbances were observed in 36% of the patients. The 5-year survival after radical surgery did not depend on the tumor size, tumor cell atypia or metastases to the regional lymph nodes. The prognosis was worse when the tumor was located in the liver. Ultrastructural features of the tumor cells were reliable criteria of the malignancy degree and tumor prognosis. The prognosis, recurrence-free interval and survival improve with an increase in the number of ultrastructurally differentiated cells and organoids in cytoplasm, and with a reduction in nuclear polymorphism and number of dark cells. The degree of histologic and ultrastructural differentiation of tumor cells may not coincide.

Apudomas metastatic to the liver: treatment by hepatic artery embolization.

Eighteen patients with various apudomas metastatic to the liver underwent hepatic artery embolization. In one group of 14 patients, hepatic artery embolization was the only antineoplastic therapy used during the study period. Three deaths occurred in this group. A partial remission of the hepatic metastases occurred in eight of the 11 living patients. In addition to hepatic artery embolization, a second group of four patients received concurrent hepatic artery infusions of chemotherapeutic agents. A partial remission occurred in three of these patients. Hepatic artery embolization may offer significant palliation for patients with apudomas metastatic to the liver by reducing the tumor bulk and thus decreasing the production of pharmacologically active substances secreted by functioning tumors. The impact of this treatment on the median survival time of patients with apudomas could not be demonstrated.

Orthotopic liver transplantation in the treatment of metastatic neuroendocrine tumors of the liver.

The place of orthotopic liver transplantation (OLT) in the management of metastatic hepatic neuroendocrine tumors has not been adequately defined. The present report is concerned with patient survival, disease recurrence, and symptom relief in 11 such patients in a single center who, at the time of transplantation, had no extrahepatic tumor. All patients obtained complete symptom relief initially but tumor recurrence was observed in 6 of the 11 cases (5 carcinoid and 1 apudoma) at a median of 11 months (range 3.5-26). Five patients have died, 4 in the carcinoid group with recurrence and one from chronic rejection in the other apudoma group. Of the 6 patients currently alive one of 2 carcinoids and one of 4 other apudomas have tumor recurrence. Recurrent deposits were found predominantly in bone and in the transplanted liver. Actuarial survival post transplant was 82% and 57% at 1 and 5 years respectively. It is concluded that OLT is effective at controlling symptoms from secreting carcinoid deposits in the liver. Although the tumor will recur in most cases, this is not necessarily associated with early return of symptoms. Prolonged disease free survival is more likely in the non carcinoid apudoma group.

Mitoxantrone in metastatic apudomas: a phase II study of the EORTC Gastro-Intestinal Cancer Cooperative Group.

We performed a phase II study with mitoxantrone in patients with carcinoid tumours, islet cell tumours and medullary carcinomas of the thyroid. Thirty-five eligible patients received mitoxantrone 12 mg m-2 i.v. every 3 weeks. Among 18 previously untreated patients, three responded (17%, 95% CI = 4-41%); no responses were achieved in 17 previously treated patients. Of the 21 patients who had carcinoid tumours, 11 were previously untreated and two achieved a response (18%, 95% CI = 2-52%). Overall response rate was 9% (95% CI = 2-23%). At a median follow-up of 43 months, median overall survival was 16 months. The median survival of 21 patients with a normal alkaline phosphatase was 29 months and 9 months for 14 patients with elevated serum levels (P = 0.005). A similar observation was noticed for gamma-glutamyltransferase (P = 0.007). We concluded that mitoxantrone is not active in APUD tumours. Elevated alkaline phosphatase and gamma-glutamyltransferase are associated with a poor prognosis.