Somatostatin analogs in oncology: A look to the future

In the past 15 years considerable advances have been made in our understand ing of the molecular pharmacology of the mechanisms whereby somatostatin an d its analogs mediate their direct and indirect antineoplastic effects. How ever, some important issues remain to be resolved, in particular the functi onal roles of the individual somatostatin receptors (SSTR-1-5) in tumor tis sue and up- or downregulation of the hSSTRs with prolonged administration o f somatostatin analogs. Answers to these questions are essential before we can maximize the therapeutic efficacy of somatostatin analogs in cancer. Fo r example, is continuous administration more or less effective than intermi ttent therapy? The role of somatostatin analogs in the management of acrome galy and to a lesser extent neuroendocrine tumors is firmly established. Th e development of depot preparations of all 3 somatostatin analogs currently available for clinical use will undoubtedly improve both patient complianc e and quality of life in patients with these conditions. There are only lik ely to be minor differences in the therapeutic efficacy of octreotide, lanr eotide and vapreotide since all three analogs exert the majority of their a ntineoplastic effects via hSSTR-2 and hSSTR-5 and at the end of the day, pr ice may well dictate which of these drugs oncologists use to provide sympto matic palliation of acromegaly and neuroendocrine tumors. Apart from some n otable exceptions, somatostatin analog therapy has proven to be very disapp ointing in the management of advanced malignancy. Improvements in the manag ement of solid tumors are likely to come only from combination therapy of s omatostatin analogs with cytotoxic agents or other hormones in both advance d malignancy and in the adjuvant setting. Clinical trials with clear-cut ob jective outcome measures and health-related quality of life assessment are needed to evaluate the therapeutic efficacy of combination treatment in adv anced malignancy and as an adjuvant to surgery. Particular attention needs to be paid to possible adverse effects of somatostatin analog therapy on th e immune response to cancer. Further studies are required to establish whet her the adverse effects of somatostatin analog therapy alone or in combinat ion with cytotoxics or other hormones can be reversed with appropriate immu nomodulatory treatment. Targeted somatostatin analog radiotherapy and chemo therapy are currently being investigated and the results of these studies a re awaited with interest. Novel approaches using combinations of somatostat in analogs with antiangiogenic drugs or gene therapy are of particular inte rest and may provide important advances in the management of cancer in the not too distant future. Copyright (C) 2001 S. Karger AG, Basel.