Details

Autor(en) / Beteiligte

• Derosa, Lisa
• Galli, Luca
• Orlandi, Paola
• Fioravanti, Anna
• Di Desidero, Teresa
• Fontana, Andrea
• Antonuzzo, Andrea
• Biasco, Elisa
• Farnesi, Azzurra
• Marconcini, Riccardo
• Francia, Giulio
• Danesi, Romano
• Falcone, Alfredo
• Bocci, Guido

Titel

Docetaxel plus oral metronomic cyclophosphamide: A phase II study with pharmacodynamic and pharmacogenetic analyses in castration‐resistant prostate cancer patients

Ist Teil von

• Cancer, 2014-12, Vol.120 (24), p.3923-3931

Ort / Verlag

Hoboken, NJ: Wiley-Blackwell

Erscheinungsjahr

2014

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• BACKGROUND Docetaxel plus prednisone is currently the standard first‐line treatment in metastatic castration‐resistant prostate cancer (mCRPC). The aim of this study was to assess the clinical activity and pharmacodynamic/pharmacogenetic profile of docetaxel plus prednisone in combination with metronomic cyclophosphamide in mCRPC patients. METHODS Forty‐one chemotherapy‐naive patients received docetaxel (60 mg/m2 intravenously every 3 weeks up to 12 cycles) and, from day 2, prednisone 10 mg/day, celecoxib 400 mg/day, and metronomic cyclophosphamide 50 mg/day, continuously. Plasma VEGF and bFGF were detected by ELISA. Real‐time PCR‐SNP analysis of VEGF gene was performed using an ABI PRISM 7900HT SDS and TaqMan SNP genotyping. RESULTS Eighty‐seven percent of patients were free of progression at 6 months. A decrease in prostate‐specific antigen ≥50% was observed in 82% of 39 evaluable patients, with a median time to progression of 12.3 months. Grade 3 adverse events were neutropenia (5%), thrombocytopenia, diarrhea, and stomatitis (2.5%). Median PFS and OS were 14.9 months (95% CI, 9.2‐15.3 months) and 33.3 months (95% CI, 23‐35.6 months), respectively. Of 11 patients (28%) with evaluable disease, 5 (44%) achieved a complete response, 2 (11%) a partial response, and 2 (11%) stable disease, whereas 2 showed disease progression. The −1154A/G VEGF polymorphism, plasma VEGF, and bFGF after the first cycle of chemotherapy may represent useful pharmacodynamic markers to predict better outcomes. CONCLUSIONS The combination of docetaxel and oral metronomic chemotherapy is effective and well tolerated in mCRPC patients and may deserve further evaluation. Cancer 2014;120:3923–3931. © 2014 American Cancer Society. The present multicenter, prospective, non‐randomized phase II clinical study demonstrates that the combination of docetaxel and prednisone plus metronomic cyclophosphamide and celecoxib is effective as a first‐line treatment in patients with mCRPC, and that it shows favorable toxicity. Moreover, the investigation of ‐1154A/G VEGF polymorphism, and of VEGF and bFGF plasma levels after the first cycle of chemotherapy suggests that these pharmacodynamic indices may be useful markers to predict a better outcome.