Neoadjuvant docetaxel before radical prostatectomy in patients with high-risk localized prostate cancer.
OBJECTIVE
To determine the clinical, pathologic, and molecular effects of neoadjuvant docetaxel chemotherapy in high-risk localized prostate cancer.


METHODS
Patients with biopsy Gleason scores of 8 to 10, serum prostate-specific antigen levels >20 ng/mL, and/or clinical stage T3 disease received weekly docetaxel (36 mg/m2) for 6 months, followed by radical prostatectomy, and were monitored with weekly visits, serum prostate-specific antigen measurements, and endorectal magnetic resonance imaging (MRI). Frozen tumor specimens were collected for microarray analysis.


RESULTS
The 19 patients enrolled received 82% of the planned chemotherapy. Toxicity was mild to moderate; fatigue and taste disturbance were common. Prostate-specific antigen declines of >50% were seen in 11 of 19 patients (58%; 95% confidence interval, 33-80%) and endorectal MRI showed maximum tumor volume reduction of at least 25% in 13 of 19 patients (68%; 95% confidence interval, 47-85%) and at least 50% in 4 patients (21%; 95% confidence interval, 6-46%). Sixteen patients completed chemotherapy and had radical prostatectomy; none achieved pathologic complete response. Microarray analysis identified coordinate up-regulation of genes involved in androgen metabolism associated with docetaxel therapy. Specifically, RNA expression for genes that decrease cellular levels of bioactive androgens was coordinately increased in response to chemotherapy.


CONCLUSIONS
Neoadjuvant docetaxel administered for 6 months before radical prostatectomy is feasible, well tolerated, and often results in prostate-specific antigen declines of >50% and decreased tumor volume on endorectal MRI. No pathologic complete responses were observed. Altered androgen metabolism may partially account for the noted declines in prostate-specific antigen and be a mechanism for chemotherapy resistance.
Febbo
Phillip G
PG
Lank Center for Genitourinary Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston Massachusetts 02115, USA.
Richie
Jerome P
JP
George
Daniel J
DJ
Loda
Massimo
M
Manola
Judith
J
Shankar
Sridhar
S
Barnes
Agnieska Szot
AS
Tempany
Clare
C
Catalona
William
W
Kantoff
Philip W
PW
Oh
William K
WK
D000328:Adult; D000728:Androgens / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D000077143:Docetaxel; D004334:Drug Administration Schedule; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D012333:RNA, Messenger / Q000096:biosynthesis; D018570:Risk Assessment; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000728:Androgens; D000972:Antineoplastic Agents, Phytogenic; D012333:RNA, Messenger; D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen