Thalidomide/estramustine/paclitaxel in metastatic androgen-independent prostate cancer.
BACKGROUND
This is a phase I/II trial of thalidomide with estramustine and paclitaxel in men with androgen-independent prostate cancer (AIPC) who underwent previous chemotherapy.


METHODS
Men with progressive AIPC were treated with oral thalidomide (200 mg, 400 mg, or 600 mg daily), intravenous paclitaxel (100 mg/m2 over 3 hours on days 3 and 10), and oral estramustine (140 mg 3 times daily on days 1-5 and days 8-12) every 21 days.


RESULTS
Phase I: first cycle dose-limiting toxicity occurred in 0 of 3 patients at 200 mg thalidomide daily, 0 of 3 at 400 mg daily, and 1 of 3 at 600 mg daily (the designated maximum tolerated dose). Phase II: twenty-nine of 38 evaluable patients (76%; 95% confidence interval, 67%-87%) experienced a 50% decrease in prostate-specific antigen level. Five of 18 patients (28%) with measurable disease exhibited an objective response. Nine of 14 patients (64%) with disease refractory to previous taxane therapy had 50% decreases in prostate-specific antigen level. Grade 3/4 adverse events included neutropenia (9 of 39 [23%]), fatigue (9 of 39 [23%]), dyspnea (8 of 39 [21%]), and thromboembolic events (7 of 39 [18%]). Cumulative dose-limiting toxicity rates were minimal (13%) with thalidomide at 200 mg daily.


CONCLUSIONS
The profile of activity of thalidomide/paclitaxel/estramustine in taxane-refractory AIPC warrants further investigation.
Mathew
Paul
P
Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. pmathew@mdanderson.org
Logothetis
Christopher J
CJ
Dieringer
Pauline Y
PY
Chen
Isan
I
Pagliaro
Lance C
LC
Bekele
Benjamin N
BN
Zhou
Xian
X
Daliani
Danai D
DD
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000009:adverse effects; D018450:Disease Progression; D004961:Estramustine / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D043823:Taxoids / Q000009:adverse effects; D013792:Thalidomide / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome
D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane; D004961:Estramustine; D013792:Thalidomide; D017430:Prostate-Specific Antigen; D017239:Paclitaxel