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/m(2) 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.
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/m(2) 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/GVEGF 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.
Authors: Romualdo Barroso-Sousa; Leonardo Gomes da Fonseca; Karla Teixeira Souza; Ana Carolina Ribeiro Chaves; Ariel Galapo Kann; Gilberto de Castro; Carlos Dzik Journal: Med Oncol Date: 2014-12-18 Impact factor: 3.064
Authors: Rebecca A Previs; Guillermo N Armaiz-Pena; Yvonne G Lin; Ashley N Davis; Sunila Pradeep; Heather J Dalton; Jean M Hansen; William M Merritt; Alpa M Nick; Robert R Langley; Robert L Coleman; Anil K Sood Journal: Mol Cancer Ther Date: 2015-10-29 Impact factor: 6.261
Authors: Janet S Rader; Michael W Sill; Jan H Beumer; Heather A Lankes; Doris Mangiaracina Benbrook; Francisco Garcia; Connie Trimble; J Tate Thigpen; Richard Lieberman; Rosemary E Zuna; Charles A Leath; Nick M Spirtos; John Byron; Premal H Thaker; Shashikant Lele; David Alberts Journal: Gynecol Oncol Date: 2017-03-10 Impact factor: 5.482
Authors: Paloma Valenzuela; Derrick Oaxaca; Teresa Di Desidero; Karla Parra; Georgialina Rodriguez; Marian Manciu; Giacomo Allegrini; Alfredo Falcone; Guido Bocci; Robert A Kirken; Giulio Francia Journal: Clin Exp Med Date: 2020-10-13 Impact factor: 3.984