OCTREOTIDE COMBINED WITH GOSERELIN IN THE THERAPY OF ADVANCED PANCREATIC-CANCER - RESULTS OF A PILOT-STUDY AND REVIEW OF THE LITERATURE

The two hormone analogues octreotide and goserelin have been shown to decelerate growth of human pancreatic cancer in vitro and in vivo. The objective of this pilot study was to investigate the efficacy and tox icity of the combination of these two agents in patients with advanced pancreatic cancer. Octreotide was injected subcutaneously in dosages increasing weekly, starting with 50 mu g twice daily, until the level of maintenance therapy of 500 mu g three times a day was reached. In a ddition, 3.8 mg goserelin acetate was administered subcutaneously at m onthly intervals. A median of 7 cycles (range 1-27 cycles) were applie d; 13 out of 14 patients entered into the study were evaluable for res ponse and all 14 were evaluated for toxicity. In one patient with init ially non-resectable pancreatic cancer, systemic therapy yielded a par tial remission lasting 9 months. The degree of tumour regression then allowed a consecutive macroscopic radical tumour resection followed by an additional 6 months of no evidence of disease while the same drug combination was continued. In an additional 9 patients, no change of d isease was observed, in some cases for a remarkably long time (up to 2 7 months). Nevertheless, the objective response rate of 7% (95% confid ence interval 0 +/- 21%) was low. In 5 patients a clear improvement in their performance status was seen soon after the start of therapy; 3 patients showed progression of the disease at first evaluation or earl ier and 1 patient was not evaluable at the time of study assessment. A ccording to the product-limit method of Kaplan and Meier, the time to progression was 3.0 +/- 1.8 months [median +/- asymptotic standard err or (ASE)] and overall survival was 6.0 +/- 1.5 months (median +/- ASE) . Toxicity was rare and only of mild to moderate degree. Overall, the regimen under investigation did not meet the criteria for sufficient a ntitumoural effectiveness. Nevertheless, this study reinforces the con cept that pancreatic cancer is principally responsive to endocrine the rapy and therefore the further investigation of hormonal manipulation seems worth while in the future.