Abstract
To determine whether the chemotherapy resistance of non-small cell lung cancer could be modified by oral dexverapamil, the D-isomer of verapamil, 54 patients were entered into a randomised phase II study of oral dexverapamil plus chemotherapy (vindesine/etoposide) (arm B) versus chemotherapy (arm A) alone in January 1994. Chemotherapy consisted of intravenous vindesine 3 mg/m2 bolus on days one and five and etoposide 140 mg/m2 on days two and four. Dexverapamil was given for six days, 1500 mg a day divided into six doses of 250 mg every four hours starting 24 h prior to chemotherapy. According to the individual tolerability, the single dose could be increased up to a maximum of 400 mg. Cycles were repeated 3 weekly up to four courses. At this stage of the analysis, 34 patients (18 in arm A and 16 in arm B) are evaluable for toxicity and response. Cardiovascular side effects were more marked in the patient group with dexverapamil. On average, the dose of dexverapamil was 1800 mg a day. There were 5 partial remissions (31.3%) and 9 no changes (56.3%) in the group with dexverapamil as opposed to 2 partial remissions (11.1%) and 6 no changes (33.3%) in the group without dexverapamil. As far as the preliminary results show, the addition of dexverapamil to vindesine/etoposide chemotherapy in this study seems to be associated with improved outcome.
Key words: NSCLC, Vindesine, Etoposide, Dexverapamil
References
- Echizen H, Brecht T, Niedergesass S, Vogelgesang B, Eichelbaum M (1985) The effect of dextro-, levo-, and racemic verapamil on atrioventricular conduction in humans. Am Heart J 109: 210–217 [DOI] [PubMed] [Google Scholar]
- Gloor H O, Urthaler F (1983) Differential effect of verapamil isomers on sinus node and AV junctional region. Am J Physiol 244: H80 [DOI] [PubMed] [Google Scholar]
- Gruber A, Peterson C, Reizenstein P (1988) D-verapamil and L-verapamil are equally effective in increasing vincristine accumulation in leucaemic cells in vitro. Int J Cancer 41: 224–226 [DOI] [PubMed] [Google Scholar]
- Kaufman A, Serur J R (1976) Optical isomers of verapamil on canine heart. Prevention of ventricular fibrillation induced by coronary artery occlusion, impaired atrioventricular conduction and negative inotropic and bronchotropic effects. Naunyn Schmiedebergs Arch Pharmacol 292: 21–27 [DOI] [PubMed] [Google Scholar]
- Keilhauer G, Emling F, Raschack M The use of R-verapamil is superior to racemic verapamil in breaking multidrug resistance of malignant cells. Proc of the 80th Annual Meeting of the American Assoc for Cancer Research Vol 30: 503
- Millward M J, Cantwell BMJ, Munro N C, Robinson A, Corris P A (1993) Oral verapamil with chemotherapy for advanced non-small cell lung cancer: a randomized study. Br J Cancer 67: 1031–1035 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pommerenke E W, Mattern J, Traugott U, Volm M (1991) Durchbrechung der Multidrug-Resistenz mit (R)-Verapamil in vitro und in vivo. Drug Res 41 (II) 855–858 [PubMed] [Google Scholar]
- Rosenthal S A, Curran W J (1990) The significance of histology in non-small cell lung cancer. Cancer Treat Rev 17: 409–425 [DOI] [PubMed] [Google Scholar]
- Tsuruo T, Tida H, Tsukagoshi S, Sakurai Y (1981) Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res 41: 1967–1972 [PubMed] [Google Scholar]