Neoadjuvant platelet derived growth factor receptor inhibitor therapy combined with docetaxel and androgen ablation for high risk localized prostate cancer.
OBJECTIVE
Platelet derived growth factor receptor inhibitor therapy improves the efficacy of taxane chemotherapy in preclinical models of prostate cancer. Men with high risk localized prostate cancer were treated with platelet derived growth factor receptor inhibitor therapy, docetaxel and hormone ablation in the preoperative setting, and clinicopathological outcomes were evaluated.


METHODS
A total of 36 men with cT2 or greater disease, Gleason grade 8-10, serum prostate specific antigen more than 20 ng/ml or cT2b and prostate specific antigen more than 10 ng/ml and Gleason 7 disease, without radiological evidence of metastases, were scheduled to receive intramuscular leuprolide, 600 mg daily oral imatinib and 30 mg/m(2) weekly docetaxel x 4 every 42 days for 3 cycles before radical prostatectomy (beta [0.02, 1.98] prior on the possibility of pathological complete remission). Unresectable disease, postoperative prostate specific antigen 0.2 ng/ml or greater, or administration of postoperative radiation or hormones were defined as treatment failure.


RESULTS
A total of 39 men were registered over 15 months. Median patient age was 57 years (range 44 to 71). Risk factors included T3 disease (22 of 39), Gleason 8-10 disease (31 of 39) and prostate specific antigen more than 20 ng/ml (12 of 39). Three men were ineligible or declined therapy, 29 of 36 (81%) received 3 cycles of therapy and 7 of 36 (19%) discontinued therapy related to toxicity. Grades 3-4 toxicity included rash (4), diarrhea (4), fatigue (6) and neutropenia (1). The surgical approach was feasible, without excessive or unusual complications such as wound dehiscence. No pathological complete remissions were defined. At a median followup of 39 months 53% were free from progression.


CONCLUSIONS
Evidence for a favorable impact of platelet derived growth factor receptor inhibitor therapy on the efficacy of neoadjuvant docetaxel and hormonal ablation in high risk localized prostate cancer was not obtained.
Mathew
Paul
P
Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA. pmathew@mdanderson.org
Pisters
Louis L
LL
Wood
Christopher G
CG
Papadopoulos
John N
JN
Williams
Dallas L
DL
Thall
Peter F
PF
Wen
Sijin
S
Horne
Erin
E
Oborn
Carol J
CJ
Langley
Robert
R
Fidler
Isaiah J
IJ
Pettaway
Curtis A
CA
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001549:Benzamides; D018572:Disease-Free Survival; D000077143:Docetaxel; D004359:Drug Therapy, Combination; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D000068877:Imatinib Mesylate; D016729:Leuprolide / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010879:Piperazines / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D011743:Pyrimidines / Q000627:therapeutic use*; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D012307:Risk Factors; D015996:Survival Rate; D043823:Taxoids / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D043823:Taxoids; D000077143:Docetaxel; D007987:Gonadotropin-Releasing Hormone; D000068877:Imatinib Mesylate; D017479:Receptors, Platelet-Derived Growth Factor; D016729:Leuprolide