Phase 1/2 study of preoperative docetaxel and mitoxantrone for high‐risk prostate cancer

• Published in: Cancer Vol. 116; no. 7; pp. 1699 - 1708
• Main Authors: Garzotto, Mark, Higano, Celestia S., O'Brien, Catherine, Rademacher, Brooks L. S., Janeba, Nicole, Fazli, Ladan, Lange, Paul H., Lieberman, Stephen, Beer, Tomasz M.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-04-2010; Wiley-Blackwell
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Adenocarcinoma - surgery; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; chemotherapy before prostatectomy; Chemotherapy, Adjuvant; Combined Modality Therapy; docetaxel; Humans; Male; Medical sciences; Middle Aged; mitoxantrone; Mitoxantrone - administration & dosage; neoadjuvant chemotherapy; Neoadjuvant Therapy; Nephrology. Urinary tract diseases; prostate cancer; Prostate-Specific Antigen - blood; Prostatectomy; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Prostatic Neoplasms - surgery; Recurrence; Risk; Taxoids - administration & dosage; Testosterone - blood; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Antineoplastic agent; chemotherapy before prostatectomy; High risk; Prostate disease; Neoadjuvant treatment; Cancerology; Surgery; Taxane derivatives; Phase II trial; Mitoxantrone; Antimitotic; Male genital diseases; Anthraquinone derivatives; Urinary system disease; Docetaxel; Malignant tumor; neoadjuvant chemotherapy; Alkylating agent; Chemotherapy; Treatment; Antimetabolic; Phase I trial; Prostatectomy; Preoperative; Prostate cancer; Cancer
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.24960

BACKGROUND:
A study was conducted to determine the 5‐year recurrence‐free survival in patients with high‐risk prostate cancer after neoadjuvant combination chemotherapy followed by surgery. Secondary endpoints included safety, pathologic effects of chemotherapy, and predictors of disease recurrence.
METHODS:
Fifty‐seven patients were enrolled in a phase 1/2 study of weekly docetaxel 35 mg/m2 and escalating mitoxantrone to 4 mg/m2 before prostatectomy. Patients were treated with 16 weeks of chemotherapy administered weekly on a 3 of every 4 week schedule. A tissue microarray, constructed from the prostatectomy specimens, served to facilitate the exploratory evaluation of biomarkers. The primary endpoint was recurrence‐free survival. Disease recurrence was defined as a confirmed serum prostate‐specific antigen (PSA) >0.4 ng/mL.
RESULTS:
Of the 57 patients, 54 received 4 cycles of docetaxel and mitoxantrone before radical prostatectomy. Grade 4 toxicities were limited to leukopenia, neutropenia, and hyperglycemia. Serum testosterone levels remained stable after chemotherapy. Negative surgical margins were attained in 67% of cases. Lymph node involvement was detected in 18.5% of cases. With a median follow‐up of 63 months, 27 of 57 (47.4%) patients recurred. The Kaplan‐Meier recurrence‐free survival at 2 years was 65.5% (95% confidence interval [CI], 53.0%‐78.0%) and was 49.8% at 5 years (95% CI, 35.5%‐64.1%). Pretreatment serum PSA, lymph node involvement, and postchemotherapy tissue vascular endothelial growth factor expression were independent predictors of early recurrence.
CONCLUSIONS:
Preoperative chemotherapy with docetaxel and mitoxantrone is feasible. Approximately half of the high‐risk patients remain free of disease recurrence at 5 years, and clinical and molecular predictors of early recurrence were identified. Cancer 2010. © 2010 American Cancer Society.
Preoperative chemotherapy with docetaxel and mitoxantrone in patients with clinically localized high‐risk prostate cancer is feasible, with approximately half of the patients remaining free of disease recurrence at 5 years. Pretreatment serum prostate‐specific antigen, lymph node involvement, and postchemotherapy tissue vascular endothelial growth factor expression were independent predictors of early recurrence.