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 toxicity of the combination of these two agents in patients with advanced pancreatic cancer. Octreotide was injected subcutaneously in dosages increasing weekly, starting with 50 micrograms twice daily, until the level of maintenance therapy of 500 micrograms three times a day was reached. In addition, 3.8 mg goserelin acetate was administered subcutaneously at monthly intervals. A median of 7 cycles (range 1-27 cycles) were applied; 13 out of 14 patients entered into the study were evaluable for response and all 14 were evaluated for toxicity. In one patient with initially non-resectable pancreatic cancer, systemic therapy yielded a partial 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 disease was observed, in some cases for a remarkably long time (up to 27 months). Nevertheless, the objective response rate of 7% (95% confidence 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 earlier and 1 patient was not evaluable at the time of study assessment. According to the product-limit method of Kaplan and Meier, the time to progression was 3.0 +/- 1.8 months [median +/- asymptotic standard error (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 antitumoural effectiveness. Nevertheless, this study reinforces the concept that pancreatic cancer is principally responsive to endocrine therapy and therefore the further investigation of hormonal manipulation seems worth while in the future.