PHASE I STUDY OF TAXOTERE IN PATIENTS WITH ADVANCED MALIGNANCIES AND VARYING DEGREES OF LIVER DYSFUNCTION
OBJECTIVES: I. Determine the maximum tolerated dose of docetaxel in patients with advanced
solid tumors and varying degrees of liver dysfunction. II. Determine the effects of liver
dysfunction in these patients on the plasma pharmacokinetics and pharmacodynamics of this
therapy. III. Determine the utility of indocyanine green clearance and lidocaine metabolism
as indicators of hepatic elimination of docetaxel in these patients.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to
liver function (normal vs mild vs moderate vs severe). Patients receive docetaxel IV over 1
hour. Courses repeat every 3 weeks in the absence of disease progression or unacceptable
toxicity. Patients who achieve complete remission (CR) receive 2 additional courses past CR.
Within each abnormal liver function stratum, cohorts of 3-6 patients receive escalating
doses of docetaxel until the maximum tolerated dose is determined. The MTD is defined as the
dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Within each
abnormal liver function stratum, more than 6 patients are treated at the MTD, if possible.
Patients in the normal liver function stratum are included as control patients and are
followed for toxicity, but do not undergo dose escalation. Patients are followed for
PROJECTED ACCRUAL: A maximum of 45 patients will be accrued for this study within 12-18
Primary Purpose: Treatment
James H. Doroshow, MD
Beckman Research Institute
United States: Federal Government
|Cancer Center and Beckman Research Institute, City of Hope||Duarte, California 91010-3000|
|USC/Norris Comprehensive Cancer Center and Hospital||Los Angeles, California 90033-0804|
|University of California Davis Cancer Center||Sacramento, California 95817|