Phase II trial of neoadjuvant docetaxel before radical prostatectomy for locally advanced prostate cancer.
OBJECTIVE
To perform a Phase II trial of docetaxel administered on a weekly schedule for 6 weeks before radical prostatectomy (RP) in patients with locally advanced prostate cancer.


METHODS
Treatment consisted of six doses of docetaxel 40 mg/m(2) intravenously administered weekly for 6 weeks followed by RP. Eligibility criteria included clinical Stage T2b, prostate-specific antigen (PSA) level 15 ng/mL or greater or Gleason sum 8 or greater, and no evidence of metastatic disease. The primary endpoint was feasibility and drug-related and surgical-related toxicities. Secondary endpoints included pre-RP PSA level, local response, pathologic outcomes, and time to PSA failure.


RESULTS
Twenty-nine patients were entered; 80% completed all 6 weeks of therapy and 97% underwent RP. The median PSA level was 12 ng/mL (range 2.5 to 43.3), the median Gleason sum was 8 (range 6 to 9), and all had Stage T2b or greater disease. A statistically significant reduction in the prechemotherapy versus postchemotherapy mean PSA level was observed (12.00 +/- 1.86 ng/mL versus 8.42 +/- 1.63 ng/mL, P <0.03), with 79% of patients experiencing some reduction and 24% a more than 50% reduction in PSA level in response to docetaxel alone. No unexpected toxicities and no intraoperative complications occurred. Pathologic analysis demonstrated residual carcinoma in all cases. Three patients (11%) had organ-confined disease, and 26 (93%) had achieved an undetectable PSA postoperatively. At a median follow-up of 23 months (range 1.5 to 36), 20 patients were disease free with no additional therapy.


CONCLUSIONS
This trial establishes the baseline effect of short-course high-dose docetaxel alone on locally advanced prostate cancer. Additional study of this paradigm with other agents alone and in combination with docetaxel seems warranted.
Dreicer
Robert
R
Department of Hematology and Medical Oncology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Magi-Galluzzi
Cristina
C
Zhou
Ming
M
Rothaermel
Jason
J
Reuther
Alwyn
A
Ulchaker
James
J
Zippe
Craig
C
Fergany
Amr
A
Klein
Eric A
EA
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D017024:Chemotherapy, Adjuvant; D003907:Dexamethasone / Q000008:administration & dosage; D000077143:Docetaxel; D006801:Humans; D008197:Lymph Node Excision; D008297:Male; D008875:Middle Aged; D011292:Premedication; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy*; D043823:Taxoids / Q000008:administration & dosage*; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D043823:Taxoids; D000077143:Docetaxel; D003907:Dexamethasone; D017430:Prostate-Specific Antigen