Phase II Study of Dovitinib in Patients with Castration-Resistant Prostate Cancer (KCSG-GU11-05)

• Published in: Cancer research and treatment Vol. 50; no. 4; pp. 1252 - 1259
• Main Authors: Choi, Yoon Ji, Kim, Hye Sook, Park, Se Hoon, Kim, Bong-Seog, Kim, Kyoung Ha, Lee, Hyo Jin, Song, Hong Suk, Shin, Dong-Yeop, Lee, Ha Young, Kim, Hoon-Gu, Lee, Kyung Hee, Lee, Jae Lyun, Park, Kyong Hwa
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Cancer Association 01-10-2018; 대한암학회
• Subjects: Aged; Aged, 80 and over; Benzimidazoles - administration & dosage; Benzimidazoles - adverse effects; Biomarkers, Tumor - metabolism; Docetaxel - therapeutic use; Drug Administration Schedule; Fibroblast Growth Factor-23; Fibroblast Growth Factors - metabolism; Humans; Male; Middle Aged; Neoplasm Metastasis; Original; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - metabolism; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Quinolones - administration & dosage; Quinolones - adverse effects; Receptor, Fibroblast Growth Factor, Type 2 - metabolism; Survival Analysis; Treatment Outcome; Vascular Endothelial Growth Factor Receptor-2 - metabolism; 의약학; Dovitinib; Biomarkers; Castration-Resistant Prostatic Neoplasm
• ISSN: 1598-2998; 2005-9256
• DOI: 10.4143/crt.2017.438

Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC).
This study was a single-arm, phase II, open-label, multicenter trial of dovitinib 500 mg/day (5-days-on/2-days-off schedule). The primary endpointwas 16-week progression-free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and prostate-specific antigen (PSA) response rate. Biomarker analyses for VEGFR2, FGF23, and FGFR2 using multiplex enzyme-linked immunosorbent assay was performed.
Forty-four men were accrued from 11 hospitals. Eighty percent were post-docetaxel. Median PSA was 100 ng/dL, median age was 69, 82% had bone metastases, and 23% had liver metastases. Median cycles of dovitinibwas 2 (range, 0 to 33). Median PFSwas 3.67 months (95% confidence interval [CI], 1.36 to 5.98) and median OS was 13.70 months (95% CI, 0 to 27.41). Chemotherapy-naïve patients had longer PFS (17.90 months; 95% CI, 9.23 to 28.57) compared with docetaxel-treated patients (2.07 months; 95% CI, 1.73 to 2.41; p=0.001) and the patients with high serum VEGFR2 level over median level (7,800 pg/mL) showed longer PFS compared with others (6.03 months [95% CI, 4.26 to 7.80] vs. 1.97 months [95% CI, 1.79 to 2.15], p=0.023). Grade 3 related adverse events were seen in 40.9% of patients. Grade 1-2 nausea, diarrhea, fatigue, anorexia, and all grade thrombocytopenia are common.
Dovitinib showed modest antitumor activity with manageable toxicities in men with mCRPC. Especially, patients who were chemo-naïve benefitted from dovitinib.