Phase I trial of PSC 833 and doxorubicin, vincristine, cyclophosphamide, and predisone (DVCP) in patients with refractory non-Hodgkinʼs lymphoma

Modulation of daunorubicin cellular resistance by combination of P-glycoprotein blockers acting on drug efflux and intracellular drug sequestration in Golgi vesicles

“…Many compounds were evaluated for Pgp‐mediated resistance modulation but most of them failed to be usable in vivo because their modulating activity appeared at concentrations generating toxic side effects. More recently, second‐generation multidrug resistance modulators were designed to avoid this inconvenience, and compounds such as the triazinopiperidine derivative S9788 (7–9), and the nonimmunosuppressive cyclosporine derivative PSC833 (10–13) were developed and evaluated in clinical trials (14–16). In addition to Pgp‐dependent drug efflux, multidrug resistance phenotype was also reported to be associated with some alteration of intracellular drug distribution with diversion of the drug from its nuclear target sites of action (17).…”