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Annals of Oncology 11:1471-1476, 2000
© 2000 European Society for Medical Oncology

research-article

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

D. Belpomme1,, S. Gauthier1, E. Pujade-Lauraine2, T. Facchini3, M.-J. Goudier4, I. Krakowski5, G. Netter-Pinon6, M. Frenay7, C. Gousset1, F. N. Marié1, M. Benmiloud1 and F. Sturtz1

1Hôpital Boucicaut Paris
2Hôpital Dieu Paris
3Polyclinique de Courlancy Reims
4Hôpital Bodélio Lorient
5Centre Alexis Vautrin, Vandoeuvreles-Nancv Meaux
6Hôpital Général Meaux
7Centre Antoine Lacassagne Nice, France

Correspondence to: Prof. D. Belpomme Oncology Department Hôpital Boucicaut 78 Rue de la Convention, 75015 Paris France, E-mail: artac.cerc{at}bcc.ap-hop-paris.fr

BACKGROUND: Verapamil (VER), a potent calcium channel blocker, has been found to overcome P-gp-mediated multidrug resistance (MDR) and to increase sensitivity to cytotoxic anticancer drugs in refractory myeloma and non-Hodgkin lymphorna. The value of VER for treating solid tumors is still a matter for debate.

PATIENTS AND METHODS: We performed a prospective study in 99 patients with anthracycline-resistant metastatic breast carcinoma (MBC), to assess the clinical effect of oral VER given in association with chemotherapy. Instead of retreating patients with anthracycline, we used a partially noncross-resistant regimen (VF), combining vindesine (VDS) and 5-fluorouracil given as a continuous infusion (5-FU CI). Patients were randomly assigned to two cohorts. One cohort (47 patients) was treated in 28-day cycles, each involving the administration of VDS (3 mg/m2 i.v. bolus on days 1 and 10) and 5-FU CI, (400 mg/m2/day i.v. from day 1 to day 10). The other cohort (52 patients) received the same VDS and 5-FU treatment and an additional oral VER treatment (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 overall survival (OS) (median OS: 323 vs. 209 days, P=0.036) and a higher response rate (27% vs. 11%, P=0.04) than those not given VER. Progression-free 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 anthracycline resistance.

5-FU continuous infusion, metastatic breast carcinoma, multidrug resistance, verapamil


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