Verapamil increases the survival of patients with anthracycline-resistant metastatic breast carcinoma

Background: Verapamil (VER), a potent calcium channel blocker, has been fou nd to overcome P-gp-mediated multi-drug resistance (MDR) and to increase se nsitivity to cytotoxic anticancer drugs in refractory myeloma and non-Hodgk in lymphoma. The value of VER for treating solid tumors is still a matter f or debate. Patients and methods: We performed a prospective study in 99 patients with anthracycline-resistant metastatic breast carcinoma (MBC), to assess the cl inical effect of oral VER given in association with chemotherapy. Instead o f retreating patients with anthracycline, we used a partially noncross-resi stant regimen (VF), combining vindesine (VDS) and 5-fluorouracil given as a continuous infusion (5-FU CI). Patients were randomly assigned to two coho rts. One cohort (47 patients) was treated in 28-day cycles, each involving the administration of VDS (3 mg/m(2) i.v. bolus on days 1 and 10) and 5-FU CI, (400 mg/m(2)/day i.v. from day 1 to day 10). The other cohort (52 patie nts) received the same VDS and 5-FU treatment and an additional oral VER tr eatment (240 mg/day divided in 2 doses), from day 1 to day 28 of each cycle . Patients were treated until progression. Results: The treatment was well tolerated and no side effects that could be attributed to VER were detected. Patients treated with VER had longer over all survival (OS) (median OS: 323 vs. 209 days, P = 0.036) and a higher res ponse rate (27% vs. 11%, P = 0.04) than those not given VER. Progression-fr ee survival (PFS) was also longer but the difference was not statistically significant (median PFS: 4.6 and 2.7 months for the VER and non-VER groups respectively, P = 0.6). Conclusions: This clinical trial demonstrates that a chemosensitizer, such as VER, can increase the survival of MBC patients with acquired anthracycli ne resistance.