D-Verapamil and Adriamycin in the treatment of advanced colorectal cancer

Abstract

One of the reasons for the primary resistance of colorectal cancer to a wide variety of cytotoxic drugs may be the high frequency of multidrug resistance (MDR) encountered in this disease [1]. Several classes of agents have been demonstrated to overcome MDR phenotype in experimental tumor systems. Verapamil (VPM) is the prototype of these drugs, but in early clinical studies it had to be recognized that VPM because of its potent effects on the cardiovascular system, could not be administered in the optimal concentration required for reversal of MDR in vitro. An attractive alternative to the use of the marketed drug Verapamil (a racemic DL mixture) is the D-isomer of VPM, which has equal resistance-reverting potential but a least 3-fold less cardiovascular potency [2]. Based on the potentially favourable therapeutic index of this second generation modulator, and histological studies indicating that colon cancer expresses high levels of p-glycoprotein that might be related to its inherent refractoriness to conventional anticancer agents, the present phase II study of DVPM plus Doxorubicin has been initiated.