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The aim of these experimental and clinical studies was to determine if verapamil helps overcome multidrug resistance in tumor cells and in cancer patients. The effect of the calcium channel blocker verapamil on the antiproliferative activity of epirubicin (Farmorubicin, Farmitalia) was followed up in in vitro studies on two constant human leukemia cell lines: CEM/O (P-gp negative) and CEM/VCR 1000 with a positive multidrug resistant (MDR) phenotype. The MTT assay was used to study the antiproliferative activity. Verapamil in concentrations of 3 and 10 micrograms/ml enhanced by 10-fold and 19-fold, respectively, the effect of epirubicin in CEM/VCR 1000 cells and had no significant effect on epirubicin activity in CEM/O. Eleven patients with measurable stage IV breast cancer, clinically resistant to anthracycline treatment, received the FEC combination (5-fluorouracil-epirubicin-cyclophosphamide) twice with verapamil pretreatment, p.o. at the doses of 1280-2560 mg. There were two complete remissions (soft tissue metastases), four partial remissions (soft tissue metastases and lung metastases), and three stable diseases. These studies confirm the possibilities of overcoming multidrug resistance by the administration of verapamil in tumor cells and in cancer patients.

The antiproliferative activity of the non-myelotoxic antitumour agent of plant origin, Thaliblastine, on two human glioma cell lines is described. Thaliblastine was added once one day following start of culture; proliferation was monitored over 7 days. The antiproliferative activity of Thaliblastine was strongly dependent on concentration and time of incubation. The ID50 of Thaliblastine in T406 and GW27 glioma lines was 5.1 micrograms/ml and 8.2 micrograms/ml (7.0 microM and 11.2 microM), respectively.

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Modern drug therapy of cancer patients is mainly combined. The possibilities of using a new non-myelo-and non-immuno-suppressive antitumor drug of natural origin, Thaliblastine (TBL)