Cyclosporin A and its analogues as modifiers of adriamycin and vincristine resistance in a multi-drug resistant human lung cancer cell line

Results of a phase III, double-blind, placebo-controlled trial of megestrol acetate modulation of P-glycoprotein-mediated drug resistance in the first-line management of small-cell lung carcinoma

“…In the laboratory, the ability to reverse MDR has been shown to be dose related with MA (Fleming et al, 1992) and other modulators including verapamil (Bellamy et al, 1988) and cyclosporin A (Twentyman et al, 1987), and this probably also applies to the clinical situation. In the clinical situation, information can be extrapolated from trials using MA as an appetite stimulant and promoter of improved quality of life.…”

A phase II study of epidoxorubicin in colorectal cancer and the use of cyclosporin-A in an attempt to reverse multidrug resistance

“…Using various methods, it has been shown that cyclosporin-A can restore the defective drug accumulation characteristic of MDR cells Nooter et al, 1989;Silberman et al, 1989). It has also been shown the cyclosporin-A can effectively restore the cytotoxicity of anthracycline drugs in MDR cells in vitro (Twentyman et al, 1987) and in vivo (Slater et al, 1986). The efficacy of reversal agents can be studied by comparing the drug accumulation of MDR cells in the presence and absence of specific reversal agents.…”

Cyclosporin A and doxorubicin-ifosfamide in resistant solid tumours: a phase I and an immunological study

“…CsA is a substrate of P-gp and can competitively inhibit this membrane protein at clinically attainable doses. Concentrations of 1000-2000ngml-' CsA are needed to reverse MDR in vitro (Twentyman et al, 1987). At these doses CsA can also suppress the induction of the DNA repair genes (Kashami-Sabet et al, 1990) and may potentiate the cytotoxicity of antineoplastic agents in human tumour cells not expressing P-gp (Larsson and Mygren, 1990).…”