Clinical, pharmacodynamic and pharmacokinetic results of a prospective phase II study on oral metronomic vinorelbine and dexamethasone in castration-resistant prostate cancer patients

• Published in: Investigational new drugs 2016-12, Vol.34 (6), p.760-770
• Main Authors: Di Desidero, Teresa, Derosa, Lisa, Galli, Luca, Orlandi, Paola, Fontana, Andrea, Fioravanti, Anna, Marconcini, Riccardo, Giorgi, Mario, Campi, Beatrice, Saba, Alessandro, Lucchesi, Sara, Felipetto, Renato, Danesi, Romano, Francia, Giulio, Allegrini, Giacomo, Falcone, Alfredo, Bocci, Guido
• Format: Article
• Language: English
• Subjects: Administration, Oral; Aged; Aged, 80 and over; Antigens; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biochemistry; Blood tests; Bone Neoplasms - drug therapy; Bone Neoplasms - secondary; Cancer therapies; Chemotherapy; Clinical trials; Creatinine; Dexamethasone - administration & dosage; Disease; Drug dosages; Drug therapy; Electrocardiography; Follow-Up Studies; Hospitals; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - secondary; Lymphatic Metastasis; Male; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Neoplasm Grading; Neoplasm Staging; Oncology; Patients; Pharmacodynamics; Pharmacokinetics; Pharmacology/Toxicology; Phase II Studies; Plasma; Prognosis; Prospective Studies; Prostate cancer; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - pathology; Regression analysis; Steroids; Survival Rate; Tissue Distribution; Toxicity; Vascular endothelial growth factor; Vinblastine - administration & dosage; Vinblastine - analogs & derivatives; Working groups
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-016-0385-0

Summary The aim of the present study was to evaluate clinical activity, and the pharmacodynamic and pharmacokinetic profiles, of oral metronomic vinorelbine (VNR) plus dexamethasone (DEX) in metastatic castration-resistant prostate cancer (mCRPC) patients. Fourty-one patients (92 % chemotherapy-resistant) received 30 mg/day VNR p.o. thrice a week plus 1 mg/day DEX p.o. until disease progression. Plasma soluble B cell antigen 7 homolog 3 (sB7-H3), vascular endothelial growth factor (VEGF), and thrombospondin-1 (TSP-1), were measured by ELISA. Plasma VNR was detected using a LC-MS-MS system. The fraction of patients free of progression, defined by criteria of the Prostate Cancer Clinical Trials Working Group 2, at 3 months was 61 %. PSA decrease ≥50 % from baseline was observed in 35 % of patients. Median PFS and OS were 4 months (95 % CI, 2.8–6.9) and 17.5 months (95 % CI, 10.8–24.5), respectively. Toxicity was mild, and no grade 4 toxicities were found. The mean plasma VNR C max ranged from 1 to 2.7 ng/ml (T max 1.1 h) and no evidence of drug accumulation was found. A moderate relationship was found between plasma sB7-H3 and PSA values ( r  = 0.565; P  = 0.0094) at the baseline. Increased PFS (11.3 vs. 2.8 months; P  = 0.0298) was observed in patients with sB7-H3 levels