ISSN:
1569-8041
Keywords:
5-FU continuous infusion
;
metastatic breast carcinoma
;
multidrug resistance
;
verapamil
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Background:Verapamil (VER), a potent calcium channel blocker, hasbeen found to overcome P-gp-mediated multi-drug resistance (MDR) and toincrease sensitivity to cytotoxic anticancer drugs in refractory myeloma andnon-Hodgkin lymphoma. The value of VER for treating solid tumors is still amatter for debate. Patients and methods:We performed a prospective study in 99patients with anthracycline-resistant metastatic breast carcinoma (MBC), toassess the clinical effect of oral VER given in association with chemotherapy.Instead of retreating patients with anthracycline, we used a partiallynoncross-resistant regimen (VF), combining vindesine (VDS) and 5-fluorouracilgiven as a continuous infusion (5-FU CI). Patients were randomly assigned totwo cohorts. One cohort (47 patients) was treated in 28-day cycles, eachinvolving the administration of VDS (3 mg/m2 i.v. bolus on days 1and 10) and 5-FU CI, (400 mg/m2/day i.v. from day 1 to day 10). Theother cohort (52 patients) received the same VDS and 5-FU treatment and anadditional oral VER treatment (240 mg/day divided in 2 doses), from day 1 today 28 of each cycle. Patients were treated until progression. Results:The treatment was well tolerated and no side effects thatcould be attributed to VER were detected. Patients treated with VER had longeroverall survival (OS) (median OS: 323 vs. 209 days, P = 0.036) anda higher response rate (27% vs. 11%, P = 0.04) thanthose not given VER. Progression-free survival (PFS) was also longer but thedifference was not statistically significant (median PFS: 4.6 and 2.7 monthsfor the VER and non-VER groups respectively, P = 0.6). Conclusions:This clinical trial demonstrates that achemosensitizer, such as VER, can increase the survival of MBC patients withacquired anthracycline resistance.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1026556119020
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