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Cancer Chemother Pharmacol. 2018 Jan;81(1):163-169. doi: 10.1007/s00280-017-3482-7. Epub 2017 Nov 21.

Dose and schedule modification are required for long-term continuation of sunitinib in Japanese patients with advanced pancreatic neuroendocrine tumors.

Author information

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, Pā€‰=ā€‰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.

KEYWORDS:

Pancreatic neuroendocrine tumors; Relative dose intensity; Sunitinib; Tyrosine kinases inhibitor

PMID:
29164297
DOI:
10.1007/s00280-017-3482-7

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