Phase 1/2 study of preoperative docetaxel and mitoxantrone for high-risk prostate cancer.
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/m(2) and escalating mitoxantrone to 4 mg/m(2) 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. (c) 2010 American Cancer Society.
Garzotto
Mark
M
Division of Urology, Oregon Health and Science University, Portland Veterans Administration Medical Center, Portland, Oregon, USA.
Higano
Celestia S
CS
O'Brien
Catherine
C
Rademacher
Brooks L S
BL
Janeba
Nicole
N
Fazli
Ladan
L
Lange
Paul H
PH
Lieberman
Stephen
S
Beer
Tomasz M
TM
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage*; D020360:Neoadjuvant Therapy; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D012008:Recurrence; D012306:Risk; D043823:Taxoids / Q000008:administration & dosage*; D013739:Testosterone / Q000097:blood
D043823:Taxoids; D000077143:Docetaxel; D013739:Testosterone; D008942:Mitoxantrone; D017430:Prostate-Specific Antigen