An active regimen of weekly paclitaxel and estramustine in metastatic androgen-independent prostate cancer.
OBJECTIVE
The efficacy of weekly high-dose paclitaxel in androgen-independent prostate carcinoma and its cytotoxic synergy with estramustine led to the evaluation of a weekly schedule of paclitaxel and estramustine in this Phase II trial.


METHODS
Patients were eligible if they had metastatic prostate adenocarcinoma with objective progression or rising prostate-specific antigen (PSA) levels despite androgen deprivation therapy and antiandrogen withdrawal. Prior radiation and/or one prior chemotherapy regimen was permitted. A Zubrod performance status of 2 or less and adequate bone marrow and hepatic and renal function were required. Estramustine was administered orally at a dose of 280 mg three times daily on days 1 to 3, 8 to 10, and 15 to 17. Paclitaxel (150 mg/m2) was administered as a 1-hour intravenous infusion on days 2, 9, and 16. Therapy was repeated every 28 days (one cycle).


RESULTS
Twenty-eight patients were enrolled (median age 71.5 years). Fifteen patients had measurable disease (nine nodal and seven visceral) and 13 had bone-only metastases. A total of 116 cycles of therapy were delivered (median 4 cycles per patient, range 1 to 12). Nine patients required dose reduction. The predominant toxicities consisted of grade 3 neuropathy in 6 patients and grade 3 and 4 neutropenia in 4 patients, with one hospitalization for febrile neutropenia. Three patients had thrombotic manifestations: one deep venous thrombosis and two non-Q wave myocardial infarctions. Of the 28 patients, 26 were assessable for response. Of 13 patients with measurable disease, 5 demonstrated a partial response (1 in the liver and 4 in the lymph nodes), and 8 of 13 patients with bone-only metastases had a 50% or greater decrease in PSA level. Three patients had a 90% or greater decline in PSA. The overall PSA response rate was 61.53% (95% confidence interval 38.1% to 74.2%). The median time to progression was 4.64 months, and the median survival was 13 months.


CONCLUSIONS
The combination of weekly estramustine and paclitaxel is active in metastatic androgen-independent prostate cancer.
Vaishampayan
Ulka
U
Division of Hematology/Oncology, Barbara Ann Karmanos Cancer Institute and Wayne State University School of Medicine, Detroit, Michigan, USA.
Fontana
Joseph
J
Du
Wei
W
Hussain
Maha
M
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004961:Estramustine / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis
D004961:Estramustine; D017239:Paclitaxel