Neoadjuvant Platelet Derived Growth Factor Receptor Inhibitor Therapy With Docetaxel And Androgen Ablation For High Risk Localized Prostate Cancer

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology
Article Date: 26 Jan 2009 - 4:00 PDT


UroToday.com - Activated platelet derived growth factor (p-PDGF) is involved in a variety of prostate cancer (CaP) processes that promote tumor progression. A group of investigators from M.D. Anderson Cancer Center evaluated neoadjuvant combination therapy using the PDGF receptor (PDGFR) inhibitor imatinib, androgen deprivation therapy and docetaxel chemotherapy in high-risk CaP patients prior to radical prostatectomy (RP). Benefit was not found.

A total of 36 patients made up the cohort that was studied. Patients had stage T3 disease, clinical stage T2 disease with a PSA >20ng/ml, Gleason score 8-10, or cT2b and PSA >10n/ml and Gleason score 7 disease. Combination therapy consisted of bicalutamide, LHRH agonist therapy, weekly intravenous docetaxel on days 1, 8, 15, 22 of every 42-day cycle and 600mg oral imatinib daily for 3 cycles. Patients underwent RP within 4 weeks of completion of docetaxel and imatinib therapy. Among the patients, 29 (81%) completed 9 to 12 doses of docetaxel with imatinib and 7 (19%) received 2 to 4 weekly doses of docetaxel with imatinib before withdrawing from the study for toxicity. Thirty-four men went on to surgery and one was found to have unresectable lymph node disease. Fifty-eight percent of the men had 1 or more dose limiting toxicities.

The difficulty of surgical dissection was rated by the surgeons as standard in 38%, moderately difficult in 35%, and very difficult in 23%. The rectal plane was the most problematic area. Median blood loss was 750cc and there were no perioperative deaths. Regarding urinary continence, 87.8% of the patients were dry or used one pad per day.

The median preoperative PSA was 0.3 after combination therapy. Treatment failure was experienced in 16 men (47%). Median progression free interval after RP was 39.7 months and 2-year progression free survival was 57%. Overall survival rate was 94%, and there were 2 disease-related deaths. There was no statistical association between the probability of a decrease in activated PDGFR and progression-free survival.

The authors should be congratulated for completing this type of study. Although not showing patient benefit, it is based upon pre-clinical mechanism and tests the hypothesis in one of the most difficult groups of CaP patients.

Mathew P, Pisters LL, Wood CG, Papadopoulos JN, Williams DL, Thall PF, Wen S, Horne E, Oborn CJ, Langley R, Fidler IJ, Pettaway CA
J Urol. 2008 Nov 12. Epub ahead of print.
doi:10.1016/j.juro.2008.09.006

Written by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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