Modular therapy approach in metastatic castration-refractory prostate cancer

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).

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.

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.

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.