MODULATION OF MULTIDRUG-RESISTANT TUMORS BY DEXVERAPAMIL

Clinical resistance of malignant tumors against cytostatic agents is a major obstacle to effective chemotherapy. A cell surface molecule (P- 170) which acts as a pump has been identified as the underlying mechan ism of the so-called multidrug resistance (MDR). Several compounds hav e been identified which can effectively block the action of P-170 and are able to render resistant tumor cells chemosensitive. Unfortunately , most modulators display intolerable side effects at therapeutic dose s and are therefore not useful clinically. Preclinical studies show th at dexverapamil (D-VPM), an optical isomer of the MDR modulator verapa mil (Isoptin(R)), is able to effectively block the function of P-170. Cardiovascular effects are significantly reduced as compared to racemi c verapamil, permitting dose escalations to plasma levels which modula te MDR in vitro assays. Promising clinical responses were observed in lymphoma patients, especially in the non-Hodgkin population. These enc ouraging trials deserve thorough succession studies.