Does sunitinib have a patient-specific dose without diminishing its antitumor effect on advanced pancreatic neuroendocrine neoplasms?
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Because it is unknown whether adjusting the dose of sunitinib can benefit patients with pancreatic neuroendocrine neoplasms (Pan-NENs), this retrospective study examined maximum tumor shrinkage rates and prognoses in patients with and without low doses of sunitinib administration.
Eighty-seven patients with metastatic and unresectable neoplasms, treated with sunitinib for > 1 month, were divided into a low-dose (LD) or high-dose (HD) group. The tumor response rates were investigated over time using computed tomography according to the response evaluation criteria in solid tumors criteria.
The LD and HD groups included 42 and 45 patients, respectively. There were no differences in baseline characteristics (tumor size, Ki-67 index, mitosis, and differentiation) between the two groups. Progressive disease (PD), stable disease (SD), and partial response (PR) were observed in 16.7, 54.8, and 28.6% of patients in the LD group, respectively, and in 13.3, 60, and 26.7% of patients in the HD group, respectively. There were no differences in tumor shrinkage rates between the two groups (p = 0.87). The 3-year progression-free survival rates for the LD and HD groups were 2.4% and 2.3%, respectively (p = 0.67), and the 3-year overall survival rates were 57.9% and 70.5%, respectively (p = 0.76). The occurrence of adverse events was similar between the two groups (61.9% vs. 60.0%, p > 0.95).
Dose reduction of sunitinib did not alter tumor shrinkage rates or prognoses for patients with advanced Pan-NENs.
KeywordsNeuroendocrine tumor Sunitinib Low dose Liver metastasis Unresectable
All pathological diagnoses were revised by Yuko Kinowaki at Department of human Pathology, Graduate school of Medicine, Tokyo Medical and Dental University.
Study concept and design: SM. Analysis and interpretation of data: SM, AK. Acquisition of data: SM, AK, TO, KO, HO, YM, DB. Drafting of the manuscript: SM, AK. Critical revision of the manuscript for important intellectual content: ST. Statistical analysis: SM. Obtained funding: AK. Administrative, technical, or material support; AK. Study supervision: MT.
This work was supported by Grant-in-Aid for Scientific Research (C) Grant Number 19K09041.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Abrams TJ, Lee LB, Murray LJ, Pryer NK, Cherrington JM (2003) SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. Mol Cancer Therap 2:471–478Google Scholar
- Fjallskog ML, Lejonklou MH, Oberg KE, Eriksson BK, Janson ET (2003) Expression of molecular targets for tyrosine kinase receptor antagonists in malignant endocrine pancreatic tumors. Clin Cancer Res 9:1469–1473Google Scholar
- Houk BE, Bello CL, Poland B, Rosen LS, Demetri GD, Motzer RJ (2010) Relationship between exposure to sunitinib and efficacy and tolerability endpoints in patients with cancer: results of a pharmacokinetic/pharmacodynamic meta-analysis. Cancer Chemotherap Pharmacol 66:357–371. https://doi.org/10.1007/s00280-009-1170-y CrossRefGoogle Scholar
- Mendel DB et al (2003) In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 9:327–337Google Scholar