Modular therapy approach in metastatic castration-refractory prostate cancer.
OBJECTIVE
The present multi-center phase II study was designed to support the hypothesis that networking agents, which bind to ubiquitous accessible targets in metastatic castration-refractory prostate cancer (CRPC) may counteract neoplasia-specific aberrant cellular functions, thereby mediating PSA response (primary endpoint).


METHODS
Patients with metastatic CRPC received low-dose chemotherapy with capecitabine 1 g twice daily plus dexamethasone 1 mg daily for 14 days every 3 weeks, COX-2 blockade with rofecoxib 25 mg (or etoricoxib 60 mg) daily combined with pioglitazone 60 mg daily until disease progression.


RESULTS
Thirty-six consecutive patients with metastatic CRPC were enrolled, of whom n = 18 (50%) had been extensively pretreated with radio- or radionuclid therapy and n = 16 (44%) with chemotherapies; n = 8 patients (22%) were medically none-fit, having an ECOG-score of 0-2. Nine of 15 patients with PSA response >50% showed objective response. Median time to PSA response was 2.4 months (range 1.0-7.3 months). Two of 9 patients responding with PSA < 4 ng/ml showed complete resolution of skeletal lesions after 9 and 16 months; 13 patients had a stable course of disease, and 5 patients experienced progressive disease. Median progression-free survival (PFS) was 4.0 months (2.8-5.1 months) and median overall survival (OS) 14.4 months (10.7-17.2 months). Toxicities according to WHO grade II were noticed in 9 patients.


CONCLUSIONS
This new combined modular therapy approach is able to induce major responses including resolution of skeletal lesions in patients with CRPC. Furthermore, the study may clinically support the above-mentioned hypothesis.
Walter
B
B
Department of Urology, University Hospital Erlangen, 91054, Erlangen, Germany. bernhard.walter@uk-erlangen.de
Rogenhofer
S
S
Vogelhuber
M
M
Berand
A
A
Wieland
W F
WF
Andreesen
R
R
Reichle
A
A
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D018450:Disease Progression; D004359:Drug Therapy, Combination; D000077613:Etoricoxib; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D007783:Lactones / Q000627:therapeutic use; D008297:Male; D009919:Orchiectomy; D000077205:Pioglitazone; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D011725:Pyridines / Q000627:therapeutic use; D013450:Sulfones / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007783:Lactones; D011725:Pyridines; D013450:Sulfones; D045162:Thiazolidinediones; C116926:rofecoxib; D003841:Deoxycytidine; D000069287:Capecitabine; D003907:Dexamethasone; D005472:Fluorouracil; D000077613:Etoricoxib; D000077205:Pioglitazone