A Phase I Study of Continuous Intravenous Infusion of PSC 833 and Vinblastine in Patients With Metastatic Renal Cancer
The Phase I clinical trial of the combination of 120-hour continuous intravenous infusion of
vinblastine with oral PSC 833 has shown activity in patients with advanced malignancies,
particularly renal cell cancer. The MTD of vinblastine in combination with the oral drink
solution of PSC 833 was determined to be 0.9 mg/m2/day for five days and 12.5 mg/kg po q 12
hours for eight days, respectively. For the soft gel capsule formulation, the MTD was
determined to be 0.6 mg/m2/day vinblastine for five days and 4 mg/kg po q 6 hours PSC 833
for eight days. Ataxia was the dose limiting toxicity. Of the 46 patients, two complete
remissions and one partial remission were seen among 29 patients with renal cell carcinoma.
In this Phase I study, patients with advanced renal carcinoma will be treated with
escalating doses of vinblastine given as a 72 hour infusion, starting at approximately 40%
of the total standard dose. A shorter infusion schedule of vinblastine was chosen since
there is evidence in other cytotoxic combinations that PSC 833 increases the AUC and
decreases the plasma clearance of chemotherapeutic agents by approximately twofold.
Cytochrome P 450 3A or CYP3A, which is the major cytochrome enzyme in the metabolism of
vinblastine and PSC 833, will be measured during the first and fourth cycle through an in
vivo test using a single intravenous dose of midazolam, a short-acting benzodiazepine.
Vinblastine and PSC 833 pharmacokinetics will be performed at the same time. For patients
with accessible lesions, tumor biopsy will be requested.
Endpoint Classification: Safety Study, Primary Purpose: Treatment
United States: Federal Government
|National Cancer Institute (NCI)||Bethesda, Maryland 20892|