Treatment of advanced and refractory breast cancer with doxorubicin, vincristine and continuous infusion of verapamil. A phase I-II clinical trial.

Abstract

Cancer cell resistance to several cytotoxic drugs, including doxorubicin and vincristine can be reduced in vitro by verapamil; this drug works at least in part by inhibitive competition for the multiple-drug resistance efflux-pump P-glycoprotein-170. To evaluate the clinical potential of this experimental concept we combined verapamil in continuous infusion with adriamycin and vincristine in the treatment of patients with advanced and anthracycline-refractory breast cancer. Sixteen patients were included and 55 treatment courses were given at different dose levels of chemotherapy; verapamil was given by continuous infusion of 0.003 mg kg-1 min-1 for 48 h. Overall, cardiac toxicity was low but a potentiation of neurotoxicity and hematotoxicity was observed. The objective response rate was 21% (3 partial responses in 16 patients) and the median survival was 6 months; these results are comparable to those of other second line treatment studies, using drugs not supposed to be cross-resistant.