Phase I study of pasireotide (SOM 230) and everolimus (RAD001) in advanced neuroendocrine tumors

被引：25

作者：

Chan, Jennifer A. ^{[1
]}

Ryan, David P. ^{[2
]}

Zhu, Andrew X. ^{[2
]}

Abrams, Thomas A. ^{[1
]}

Wolpin, Brian M. ^{[1
]}

Malinowski, Paige ^{[1
]}

Regan, Eileen M. ^{[1
]}

Fuchs, Charles S. ^{[1
]}

Kulke, Matthew H. ^{[1
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[2] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA

来源：

关键词：

SOMATOSTATIN ANALOGS; PITUITARY-ADENOMAS; CELL-PROLIFERATION; GLUCAGON-SECRETION; CARCINOID-SYNDROME; OCTREOTIDE; MANAGEMENT; EFFICACY; THERAPY; GROWTH;

D O I：

10.1530/ERC-11-0382

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Octreotide and everolimus have demonstrated efficacy in neuroendocrine tumors. Pasireotide is a somatostatin analog with binding affinity to a broader range of somatostatin receptor subtypes than octreotide. We performed a phase I study to evaluate the safety and feasibility of combining pasireotide with everolimus in patients with advanced neuroendocrine tumors. Cohorts of patients with advanced neuroendocrine tumors were treated with escalating doses of pasireotide (600-1200 mu g s.c. b.i.d., followed by pasireotide LAR 40-60 mg i.m. monthly) and everolimus (5-10 mg daily). Twenty-one patients were treated. Dose-limiting toxicities consisting of grade 3 rash and grade 3 diarrhea were observed. Twelve patients were safely treated at the maximum protocol-defined dose level of pasireotide LAR 60 mg i.m. monthly and everolimus 10 mg daily. Hyperglycemia was common; other observed toxicities were consistent with the known toxicities of either agent alone. Partial tumor response was observed in one patient; 17 (81%) patients experienced at least some tumor regression as their best response to therapy. In conclusion, pasireotide LAR 60 mg i.m. monthly in combination with everolimus 10 mg daily is feasible and associated with preliminary evidence of antitumor activity in patients with advanced neuroendocrine tumors. Further studies evaluating this combination are warranted. Endocrine-Related Cancer (2012) 19 615-623

引用

页码：615 / 623

页数：9

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