The first clinical use of depot buserelin for advanced prostatic carcinoma

Summary The agonist analogues of the gonadotrophin-releasing hormone now provide an alternate medical treatment of prostatic cancer. For effect repeated administration is required, either by five or six times daily intranasal or once daily subcutaneous treatment. There is an obvious disadvantage to such regimens in elderly patients who may have difficulty complying with therapy. In order to circumvent these diffuculties, sustained release formulations of the agonist analogues have been synthesized. We report the first clinical use of a long-acting formulation of D-Ser (TBU)⁶-LHRH Ethylamide (buserelin) using a novel polymer material. Twelve symptomatic patients with previously untreated carcinoma of the prostate were treated with depot buserelin, administered once monthly. In all patients, depot buserelin suppressed serum testosterone into the range seen in castrate men at a rate equivalent to that provided by five times daily intranasal therapy. No significant increase in serum testosterone, luteinizing hormone or follicle-stimulating hormone concentrations occurred during the period of follow-up. Long-acting formulations of buserelin offer an advance in the management of prostatic cancer with agonist analogues of the gonadotrophin-releasing hormone.     

Statistical analysis of the in-vitro action of combination antiviral agents

Similar to the chemotherapy of bacterial infections, with the advanced development of virostatics a combination of antiviral agents is supposed to be introduced into the causal treatment of viral illness. The present studies explain a method for in vitro testing of virostatic combinations in cell cultures. The principle of the method is based on the checkerboard-technique used to test antibiotic combinations. As example the combination of trisodium phosphonoformate with bromovinyl-2'-deoxyuridine, acyclovir or 2-hexadecylglycero-3-phosphocholine was tested against herpes simplex virus, type 1. For evaluation of the test results the so-called reduction dose 50 (RD50) was introduced. The RD50 corresponds to this substance concentration, which reduces alone or in combination with a second virostatic the virus concentration used in the test system to its TCID50. With analogy to the calculation of infectious doses the computation of the RD50 was performed by using the method of Spearman and Kaerber. The calculated values allow the comparability of the antiviral activity of substances and their combinations. Corresponding to testing of antibiotics the further analysis of combinations was carried out by calculation of fractional inhibitory concentration (FIC), synergy factors (SF), and the construction of isobolograms. In this way, indifferent, synergistic and antagonistic effects of substance combination should be determined.