Phase II trial of 96-hour paclitaxel plus oral estramustine phosphate in metastatic hormone-refractory prostate cancer.
OBJECTIVE
To evaluate the antitumor activity of 96-hour paclitaxel and daily oral estramustine phosphate (EMP) in patients with metastatic hormone-refractory prostate cancer (HRPC).


METHODS
Thirty-four patients with adenocarcinoma of the prostate that progressed after one or more hormonal therapies and a trial of antiandrogen withdrawal were enrolled onto this phase II trial. Patients received paclitaxel 120 mg/m2 by 96-hour intravenous (i.v.) infusion on days 1 through 4 of each 21-day cycle, together with daily oral EMP 600 mg/m2/d, continuously.


RESULTS
Four of nine patients with measurable disease had objective responses (one complete response [CR] and three partial responses [PRs]) in liver (two patients) or nodes (two patients) of 2, 6, 8, and 20 months' duration. Of 25 assessable patients with metastases limited to bone, 14 had a > or = 50% decline in pretreatment prostate-specific antigen (PSA) level sustained for at least 6 weeks and seven had a > or = 80% decline. Overall, 17 of 32 patients (53.1%) with elevated pretreatment PSA levels had a > or = 50% decline of PSA and nine (28.1%) had a > or = 80% decrease. The main toxicities (> or = grade 2) were nausea, fluid retention, and fatigue, which occurred in 33%, 33%, and 24.2% of patients. Median time to progression, based on increasing PSA level and other clinical criteria, was 22.5 weeks. The estimated median overall survival time is 69 weeks.


CONCLUSIONS
The combination of EMP and 96-hour paclitaxel is an active regimen for patients with HRPC. These results further support the therapeutic strategy of combining agents that impair microtubule function by complementary mechanisms.
Hudes
G R
GR
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA. g_hudes@fccc.edu
Nathan
F
F
Khater
C
C
Haas
N
N
Cornfield
M
M
Giantonio
B
B
Greenberg
R
R
Gomella
L
L
Litwin
S
S
Ross
E
E
Roethke
S
S
McAleer
C
C
D000230:Adenocarcinoma / Q000188:drug therapy*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004961:Estramustine / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D004961:Estramustine; D017239:Paclitaxel