Title

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

Authors

Lisa Derosa, University Hospital of Pisa
Luca Galli, University Hospital of Pisa
Paola Orlandi, University of Pisa
Anna Fioravanti, University of Pisa
Teresa Di Desiderio, University of Pisa
Andrea Fontana, University Hospital of Pisa
Andrea Antonuzzo, University Hospital of Pisa
Elisa Biasco, University Hospital of Pisa
Azzurra Farnesi, University Hospital of Pisa
Riccardo Marconcini, University Hospital of Pisa
Giulio Francia, University of Texas at El PasoFollow
Romano Danesi, University of Pisa
Alfredo Falcone, University Hospital of Pisa
Guido Bocci, University of Pisa

Publication Date

1-1-2014

Document Type

Article

Comments

Derosa, L. , Galli, L. , Orlandi, P. , Fioravanti, A. , Di Desidero, T. , Fontana, A. , Antonuzzo, A. , Biasco, E. , Farnesi, A. , Marconcini, R. , Francia, G. , Danesi, R. , Falcone, A. and Bocci, G. (2014), Docetaxel plus oral metronomic cyclophosphamide: A phase II study with pharmacodynamic and pharmacogenetic analyses in castration‐resistant prostate cancer patients. Cancer, 120: 3923-3931. doi:10.1002/cncr.28953

Abstract

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/m2intravenously 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.