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

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)....

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Cancer Association 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192917/
https://www.ncbi.nlm.nih.gov/pubmed/29334610
http://dx.doi.org/10.4143/crt.2017.438
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author 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
author_facet 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
author_sort Choi, Yoon Ji
collection PubMed
description 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.
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spelling pubmed-61929172018-10-24 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 Cancer Res Treat Original Article 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. Korean Cancer Association 2018-10 2018-01-02 /pmc/articles/PMC6192917/ /pubmed/29334610 http://dx.doi.org/10.4143/crt.2017.438 Text en Copyright © 2018 by the Korean Cancer Association This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
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)
title Phase II Study of Dovitinib in Patients with Castration-Resistant Prostate Cancer (KCSG-GU11-05)
title_full Phase II Study of Dovitinib in Patients with Castration-Resistant Prostate Cancer (KCSG-GU11-05)
title_fullStr Phase II Study of Dovitinib in Patients with Castration-Resistant Prostate Cancer (KCSG-GU11-05)
title_full_unstemmed Phase II Study of Dovitinib in Patients with Castration-Resistant Prostate Cancer (KCSG-GU11-05)
title_short Phase II Study of Dovitinib in Patients with Castration-Resistant Prostate Cancer (KCSG-GU11-05)
title_sort phase ii study of dovitinib in patients with castration-resistant prostate cancer (kcsg-gu11-05)
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192917/
https://www.ncbi.nlm.nih.gov/pubmed/29334610
http://dx.doi.org/10.4143/crt.2017.438
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