Paclitaxel plus estramustine in metastatic hormone-refractory prostate cancer.
Combination antimicrotubule therapy with estramustine phosphate (EMP) and vinblastine has reproducible activity in metastatic hormone-refractory prostate cancer (HRPC) with an objective response rate of 31%. Although paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) by 24-hour infusion was inactive in HRPC, 0.5 to 1.0 nmol/L concentrations of paclitaxel combined with EMP exerted synergistic cytotoxicity in DU-145 androgen-independent human prostate cancer cell lines. Based on these results, we treated 24 patients with HRPC using the combination of paclitaxel 120 to 140 mg/m2 by 96-hour intravenous infusion every 3 weeks plus daily oral EMP at 600 mg/m2/d. Of seven patients with measurable soft tissue metastases, three have attained partial responses and a fourth patient is nearing partial response status. Of 16 patients with bone-only disease evaluated by change in serum prostate-specific antigen levels, 11 patients (68.8%) have had decreases of > or = 50% from pretreatment baseline. The prostate-specific antigen decrease has exceeded 80% in six of 16 (37.5%) patients. For all 23 evaluable patients, the prostate-specific antigen has decreased by > or = 50% in 15 (65.2%) and by > or = 80% in eight (34.7%). Grade 4 leukopenia occurred in one of 21 patients treated at the paclitaxel dose of 120 mg/m2/96 hr and one of three patients treated at 140 mg/m2/96 hr. The incidence of nausea (50%) and peripheral edema (37.5%) was similar to that associated with single-agent EMP. These results demonstrate that 96-hour paclitaxel plus EMP is active in HRPC and provide further evidence that the rational combination of antimicrotubule agents leads to synergistic antitumor activity in HRPC.
D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000556:secondary; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D004961:Estramustine / Q000008:administration & dosage; D005221:Fatigue / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D008297:Male; D009325:Nausea / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome
D006728:Hormones; D004961:Estramustine; D017430:Prostate-Specific Antigen; D017239:Paclitaxel