PHASE-I AND PHARMACOLOGICAL STUDY OF ESTRAMUSTINE PHOSPHATE AND SHORTINFUSIONS OF PACLITAXEL IN WOMEN WITH SOLID TUMORS

Purpose: We sought to determine the tolerance of estramustine phosphat e (EMP) combined with a 3-hour paclitaxel infusion in women with solid paclitaxel-pretreated solid tumors. paclitaxel pharmacology was to be studied at the recommended phase II dose. Patients and Methods: Pacli taxel was administered to cohorts of at least three assessable patient s at doses of 150, 180, 210, and 225 mg/m(2), while EMP was given at 9 00 and 1,200 mg/m(2)/d in divided doses orally for 2 days preceding an d on the day of paclitaxel. The pharmacologic study was performed at 2 25 mg/m(2) paclitaxel given in the absence and 3 weeks later in the pr esence of EMP 900 mg/m(2)/d. Results: Thirty-eight patients received a total of 178 courses. Grade 3 nausea, vomiting, and diarrhea were com mon at EMP 1,200 mg/m(2) and paclitaxel 225 mg/m(2); this was consider ed the maximum-tolerated dose. Since these toxicities appeared related to EMP, the pharmacologic study used a dose of 900 mg/m(2) of this ag ent with 225 mg/m(2) paclitaxel. Antitumor activity was documented aga inst breast and ovarian cancers at all levels. Paclitaxel pharmacokine tics without and with EMP did not differ. Conclusion: EMP 900 mg/m(2) for 3 days and 225 mg/m(2) paclitaxel by 3-hour infusion are well tole rated; antitumor activity was seen in women with paclitaxel-pretreated solid tumors. This apparent enhancement of antitumor effects is unlik ely to be mediated by P-glycoprotein. J Clin Oncol 16:2959-2963. (C) 1 998 by American Society of Clinical Oncology.