Lingaku Lee1,2, Tetsuhide Ito3,4, Hisato Igarashi3, Masami Miki3, Nao Fujimori3, Ken Kawabe3, Robert T Jensen5, Yoshihiro Ogawa3. 1. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. frkn505@gmail.com. 2. Digestive Diseases Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. frkn505@gmail.com. 3. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. 4. Neuroendocrine Tumor Centre, Sanno Hospital, International University of Health and Welfare, Fukuoka, Japan. 5. Digestive Diseases Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Abstract
PURPOSE: This study aimed to clarify the efficacy and safety of sunitinib in Japanese patients with pancreatic neuroendocrine tumors (PNET), especially by focusing on dose and schedule modification. METHODS: Sixteen patients with advanced PNET treated with sunitinib were reviewed retrospectively. Efficacy was evaluated by progression-free survival (PFS) and objective tumor response. Toxicity profile was assessed regularly. Correlation between relative dose intensity (RDI) and treatment period was also evaluated. RESULTS: The median PFS was 25.8 months, and the probability of PFS at 1-year was 92%. The objective response rate and clinical benefit rate were 44% and 69%, respectively. The common adverse drug reactions (ADRs) were hand-foot syndrome (88%), neutropenia (75%), leucopenia (75%), and diarrhea (63%). Due to the development of severe ADRs, 81% required dose reduction and 31% discontinued sunitinib treatment, respectively. Prolonged treatment period was significantly correlated with decreased RDI (Spearman r = - 0.57, P = 0.022). The median RDI among 9 patients whom continued sunitinib more than 1 year was 49%. CONCLUSIONS: Sunitinib showed significant clinical benefit in Japanese patients with advanced PNET in the real-world clinical setting. Successful management of ADRs with appropriate dose reduction and interruption can enable long-term continuation of sunitinib.
PURPOSE: This study aimed to clarify the efficacy and safety of sunitinib in Japanese patients with pancreatic neuroendocrine tumors (PNET), especially by focusing on dose and schedule modification. METHODS: Sixteen patients with advanced PNET treated with sunitinib were reviewed retrospectively. Efficacy was evaluated by progression-free survival (PFS) and objective tumor response. Toxicity profile was assessed regularly. Correlation between relative dose intensity (RDI) and treatment period was also evaluated. RESULTS: The median PFS was 25.8 months, and the probability of PFS at 1-year was 92%. The objective response rate and clinical benefit rate were 44% and 69%, respectively. The common adverse drug reactions (ADRs) were hand-foot syndrome (88%), neutropenia (75%), leucopenia (75%), and diarrhea (63%). Due to the development of severe ADRs, 81% required dose reduction and 31% discontinued sunitinib treatment, respectively. Prolonged treatment period was significantly correlated with decreased RDI (Spearman r = - 0.57, P = 0.022). The median RDI among 9 patients whom continued sunitinib more than 1 year was 49%. CONCLUSIONS:Sunitinib showed significant clinical benefit in Japanese patients with advanced PNET in the real-world clinical setting. Successful management of ADRs with appropriate dose reduction and interruption can enable long-term continuation of sunitinib.