Etoposide (VP-16) in the treatment of lung cancer

Abstract

Within the last decade numerous investigations have been carried out in order to evaluate the clinical usefulness of VP-16* (Etoposide), (Vepiside), (4’-demethylepipodophyllotaxing-D-ethylidene glucoside) in the treatment of lung cancer. During this period it has become evident that VP-16 is one of the most active cytostatic agents for small cell bronchogenic carcinoma (SCG). However, its potency in the treatment of the other types of lung cancer (NSCLC) is arguable. In the early 1970s observations in a variety of experimental animal models showed that the effectiveness of VP-16 was closely dependent upon the dose and schedule of administration (14). In addition it was found to have a considerable synergistic potential when administered in conjunction with other cytostatic compounds such as cyclophosphamide; 1,3 bis (2 chlorethyl)-1-nitrosourea (BCNU) or cis-diamminedichloroplatinum (&-platinum) (15, 38). Both scheduling and the potential synergy of drug combinations might thus influence the clinical effectiveness of VP-16. The route of administration (peroral or intravenous) is a third variable which may be ofimportance when analysing the results of treatment. Creaven (11) in a review of the pharmacokinetics of VP-16 concludes that the gastrointestinal absorption is variable, but greater than 50% and may approach 100%. The plasma half-life ofVP16 has been found to be 11 h by means of a radioisotope method. D’Incalci ( 13) using HPLC found a much shorter half life (7 h). The pharmacokinetics of capsules and ampoules was examined in 8 patients. A bioavailability of 57% (27-137) and 91% (48-149) respectively of that found after iv. administration indicates a wide individual variation. This review aims to analyse critically the importance of VP-16 in the treatment of lung cancer and in particular the impact the three variables discussed above may have on the variability of the many results now available. Only studies which have specifically attempted to define the importance ofVP-16 in any treatment are included. Consequently