Cancer Treatment Today

A Phase III study in 2008   concluded that Sunitinib has antitumor activity in pancreatic neuroendocrine tumors; its activity against carcinoid tumors could not be definitively determined in this nonrandomized study. An editorial by Bajetta et al in the Journal of Clinical Oncology questioend whether results for neuroendocrine cancer can be generalized to the more benign carcinoid subtypes. The Phase III clinical trial was among 171 patients who had experienced cancer progression. Half the patients were treated with Sutent, and half were treated with a placebo.

Progression-free survival was 11.4 months among patients treated with Sutent and 5.5 months among patients treated with placebo.
Patients treated with Sutent also experienced better overall survival than patients treated with placebo.
The most common serious side effect of Sutent was neutropenia (a low white blood cell count), which affected 12% of patients.
These results suggest that Sutent may improve outcomes among patients with advanced pancreatic neuroendocrine tumors. This study was publisehd in the NEJM of February 10, 2011 but NCCN has not incorporated the recommendation for Sutent as of March 2nd, 2011. In December 2010,  he European Commission has approved SUTENT® (sunitinib malate) for the treatment of unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumors (NET) with disease progression in adults. In May 2011, U.S. Food and Drug Administration (FDA) has approved SUTENT® (sunitinib malate) as the first anti-VEGF therapy to treat progressive, well-differentiated pancreatic neuroendocrine tumors (NET) in patients with unresectable locally advanced or metastatic disease. There seems to be little medical rationale to restrict this drug to pancreatic NET cancer, especially in patients with metastatic disease. A phase II study(Hobday et al) showed that sorefnib is active in NET from other sites, albeit with significant toxicity.

 REFERENCES:
Raymond E, Niccoli-Sire P, Bang Y et al. Updated results of the phase III trial of sunitinib (SU) versus placebo (PBO) for treatment of advanced pancreatic neuroendocrine tumors (NET). Presented at the 2010 ASCO Gastrointestinal Cancers Symposium. January 22-24, 2010, Orlando, FL. Abstract 127.

Emilio Bajetta, Valentina Guadalupi, Giuseppe Procopio, Activity of Sunitinib in Patients With Advanced Neuroendocrine Tumors
JCO Jan 10, 2009:319-320

Matthew H. Kulke, Heinz-Josef Lenz, Neal J. Meropol, James Posey, David P. Ryan, Joel Picus, Emily Bergsland, Keith Stuart, Lesley Tye, Xin Huang, Jim Z. Li, Charles M. Baum, Charles S. Fuchs Activity of Sunitinib in Patients With Advanced Neuroendocrine Tumors JCO July 10, 2008 vol. 26 no. 20 3403-3410
Kulke MH, Lenz H-J, Meropol NJ, et al: Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol 26:3403-3410, 2008

AUPavel M, Baudin E, Couvelard A, Krenning E,Öberg K, Steinmüller T, Anlauf M, Wiedenmann B, Salazar R, ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary.Barcelona Consensus Conference participants SONeuroendocrinology. 2012;95(2):157-76. Epub 2012 Feb 15.

T. J. Hobday, J. Rubin, K. Holen, J. Picus, R. Donehower, R. Marschke, W. Maples, R. Lloyd, M. Mahoney, C. Erlichman MC044h, a phase II trial of sorafenib in patients (pts) with metastatic neuroendocrine tumors (NET): A Phase II Consortium (P2C) study.Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 4504