Phase II Study of Dovitinib in Patients with Castration-Resistant Prostate Cancer (KCSG-GU11-05).
- Author:
Yoon Ji CHOI
1
;
Hye Sook KIM
;
Se Hoon PARK
;
Bong Seog KIM
;
Kyoung Ha KIM
;
Hyo Jin LEE
;
Hong Suk SONG
;
Dong Yeop SHIN
;
Ha Young LEE
;
Hoon Gu KIM
;
Kyung Hee LEE
;
Jae Lyun LEE
;
Kyong Hwa PARK
Author Information
- Publication Type:Original Article
- Keywords: Dovitinib; Castration-Resistant Prostatic Neoplasm; Biomarkers
- MeSH: Anorexia; Biomarkers; Carcinogenesis; Castration; Diarrhea; Disease-Free Survival; Enzyme-Linked Immunosorbent Assay; Fatigue; Fibroblast Growth Factors; Humans; Liver; Male; Multicenter Studies as Topic; Nausea; Neoplasm Metastasis; Prostate*; Prostate-Specific Antigen; Prostatic Neoplasms*; Prostatic Neoplasms, Castration-Resistant; Receptors, Fibroblast Growth Factor; Receptors, Platelet-Derived Growth Factor; Receptors, Vascular Endothelial Growth Factor; Thrombocytopenia
- From:Cancer Research and Treatment 2018;50(4):1252-1259
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: 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). MATERIALS AND METHODS: 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 endpoint was 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. RESULTS: 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 dovitinib was 2 (range, 0 to 33). Median PFS was 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. CONCLUSION: Dovitinib showed modest antitumor activity with manageable toxicities in men with mCRPC. Especially, patients who were chemo-naïve benefitted from dovitinib.
