Phase II study of dovitinib in patients with castration-resistant prostate cancer (KCSG-GU11-05)

Yoon Ji Choi, 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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1252-1259
Number of pages8
JournalCancer Research and Treatment
Volume50
Issue number4
DOIs
Publication statusPublished - 2018 Oct 1

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Castration
Prostatic Neoplasms
docetaxel
Confidence Intervals
Disease-Free Survival
Prostate-Specific Antigen
Neoplasm Metastasis
Platelet-Derived Growth Factor Receptors
Fibroblast Growth Factor Receptors
Vascular Endothelial Growth Factor Receptor
Survival
Fibroblast Growth Factors
Anorexia
Thrombocytopenia
Nausea
Multicenter Studies
Fatigue
4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one
Diarrhea
Appointments and Schedules

Keywords

  • Biomarkers
  • Castration-resistant prostatic neoplasm
  • Dovitinib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Phase II study of dovitinib in patients with castration-resistant prostate cancer (KCSG-GU11-05). / 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.

In: Cancer Research and Treatment, Vol. 50, No. 4, 01.10.2018, p. 1252-1259.

Research output: Contribution to journalArticle

Choi, YJ, Kim, HS, Park, SH, Kim, BS, Kim, KH, Lee, HJ, Song, HS, Shin, DY, Lee, HY, Kim, HG, Lee, KH, Lee, JL & Park, KH 2018, 'Phase II study of dovitinib in patients with castration-resistant prostate cancer (KCSG-GU11-05)', Cancer Research and Treatment, vol. 50, no. 4, pp. 1252-1259. https://doi.org/10.4143/crt.2017.438
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. / Phase II study of dovitinib in patients with castration-resistant prostate cancer (KCSG-GU11-05). In: Cancer Research and Treatment. 2018 ; Vol. 50, No. 4. pp. 1252-1259.
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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-na{\"i}ve 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-na{\"i}ve benefitted from dovitinib.",
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T1 - Phase II study of dovitinib in patients with castration-resistant prostate cancer (KCSG-GU11-05)

AU - Choi, Yoon Ji

AU - Kim, Hye Sook

AU - Park, Se Hoon

AU - Kim, Bong Seog

AU - Kim, Kyoung Ha

AU - Lee, Hyo Jin

AU - Song, Hong Suk

AU - Shin, Dong Yeop

AU - Lee, Ha Young

AU - Kim, Hoon Gu

AU - Lee, Kyung Hee

AU - Lee, Jae Lyun

AU - Park, Kyong Hwa

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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.

AB - 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.

KW - Biomarkers

KW - Castration-resistant prostatic neoplasm

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