Safety and effectiveness of neoadjuvant luteinizing hormone-releasing hormone agonist plus low-dose estramustine phosphate in high-risk prostate cancer: a prospective single-arm study.
BACKGROUND
Radical prostatectomy (RP) has limited cancer control potential for the patient with high-risk prostate cancer (Pca). We prospectively examined the efficacy and safety of neoadjuvant therapy with luteinizing hormone-releasing hormone (LHRH) agonist + low-dose estramustine phosphate (EMP) (LHRH+EMP) followed by RP.


METHODS
High-risk Pca was defined by the D'Amico stratification system. A total of 142 patients with high-risk Pca were enrolled in this trial from September 2005 to March 2011. The LHRH+EMP therapy included administration of LHRH agonist and 280 mg day(-1) EMP for 6 months before RP. Pathological cancer-free (pT0) rate on the surgical specimen was the primary end point. Secondary end points were PSA-free survival and toxicity.


RESULTS
The average patient age was 67.4 years (interquartile range (IQR) 72, 65) and the median initial PSA level was 14.80 ng ml(-1) (IQR 26.22, 7.13). The median Gleason score was 9 (IQR 9, 7) and 97 patients (68.3%) had clinical stage T2c or T3. All patients completed 6 months of LHRH+EMP neoadjuvant therapy with no delays in RP. Seven patients (4.9%) achieved pT0. Surgical margins were negative in 125 patients (87.0%). At a median follow-up period of 34.9 months, PSA-free survival was 84.3%. No serious adverse events were reported during the study and there were no toxicity-related deaths.


CONCLUSIONS
Six months of LHRH+EMP neoadjuvant therapy followed by RP is safe and oncological outcomes are acceptable. Although this study was a single-arm trial with a relatively short follow-up, this treatment may have a potential to improve PSA-free survival in high-risk Pca patients. Further clinical trials are warranted.
Department of Urology, Hirosaki University, Graduate School of Medicine, Hirosaki, Japan.
T
T
Koie
C
C
Ohyama
H
H
Yamamoto
S
S
Hatakeyama
T
T
Yoneyama
Y
Y
Hashimoto
N
N
Kamimura
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004961:Estramustine / Q000008:administration & dosage*; D005500:Follow-Up Studies; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage* / Q000819:agonists; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000473:pathology / Q000601:surgery
D018931:Antineoplastic Agents, Hormonal; D007987:Gonadotropin-Releasing Hormone; D004961:Estramustine; D017430:Prostate-Specific Antigen