Trial Information

A Phase I Study of Infusional Chemotherapy With the P-Glycoprotein Antagonist PSC 833

The clinical study entitled "A Phase I Study of Infusional Chemotherapy with the
P-glycoprotein Antagonist PSC 833" seeks to determine the maximum tolerated dose for a
proposed P-glycoprotein antagonist, PSC 833. PSC 833 is a cyclosporine analogue which is
purportedly non-nephrotoxic and non-immunosuppressive. It has been shown in in vitro
studies to enhance chemosensitivity as well as cyclosporine and to be far better at
increasing intracellular drug accumulation than the concentrations of verapamil which are
clinically achievable. The purpose of this study is to define the maximum tolerated dose in
combination with vinblastine, and to determine how the drug affects the pharmacokinetics of
vinblastine. PSC 833 will most likely reduce the clearance of vinblastine, as reported for
the parent compound, cyclosporine. This effect will increase the area under the curve (AUC)
of vinblastine, may increase toxicity, and requires that the escalation scheme for PSC 833
be a conservative one. Initially, a 120 hour infusion of vinblastine will be given alone.
Then 8 days of PSC 833 will follow to allow monitoring of adverse effects of PSC 833 alone.
This first cycle of vinblastine will be given in the absence of PSC 833; in second and
subsequent cycles both agents will be combined. Escalation of the PSC 833 will continue
until a target concentration is reached, or until the maximum tolerated dose is reached.
Clinical responses will be monitored in order to provide the best possible medical care to
our patients.