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Well-differentiated neuroendocrine tumors (NETs) can be subdivided into carcinoid and pancreatic NETs (pancNETs). Although these tumors share many morphologic and clinical characteristics, carcinoid tumors appear to be far less sensitive to therapeutic agents than pancNETs, and recent advances approved for pancNETs have not been submitted for FDA approval in patients with carcinoid tumors. Treatment options for patients with advanced pancNETs are multidisciplinary and include surgical resection, liver-directed therapies, and systemic therapies. Cytotoxic therapies, such as temozolomide, fluorouracil, oxaliplatin, and streptozocin-based chemotherapy regimens, are active against some pancNETs, and can play a role in the palliation of patients with advanced disease and symptoms related to tumor bulk. Two therapies were recently approved for progressive well-differentiated pancNETs: sunitinib and everolimus. Both agents showed improved progression-free survival in patients with progressive pancNETs, but can also result in nontrivial toxicities, and therefore should only be considered in patients with progressing and advanced or symptomatic disease. This article discusses these recent trials and provides an update of systemic treatment options in patients with well-differentiated pancNETs.

Standard therapy for locally advanced rectal cancer (LARC) is preoperative chemoradiotherapy and postoperative chemotherapy. At Memorial Sloan-Kettering Cancer Center (MSKCC) the authors began offering FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) as initial treatment for patients with high-risk LARC to target micrometastases while treating the primary tumor. The purpose of this study is to report the safety and efficacy of initial FOLFOX given before chemoradiotherapy on tumor downsizing and pathologic complete response (pathCR) in LARC. The records of patients with stage II/III rectal cancer treated at MSKCC between 2007 and 2012 were reviewed. Of approximately 300 patients with LARC treated at MSKCC, 61 received FOLFOX as initial therapy. Of these 61 patients, 57 received induction FOLFOX (median 7 cycles) followed by chemoradiation, and 4 experienced an excellent response, declined chemoradiation, and underwent total mesorectal excision (TME). Twelve of the 61 patients did not undergo TME: 9 had a complete clinical response (CCR), 1 declined despite persistent tumor, 1 declined because of comorbidities, and 1 developed metastatic disease. Among the 61 patients receiving initial FOLFOX, 22 (36%) had either a pathCR (n=13) or a CCR (n=9). Of the 49 patients who underwent TME, all had R0 resections and 23 (47%) had tumor response greater than 90%, including 13 (27%) who experienced a pathCR. Of the 28 patients who received all 8 cycles of FOLFOX, 8 experienced a pathCR (29%) and 3 a CCR (11%). No serious adverse events occurred that required a delay in treatment during FOLFOX or chemoradiation. FOLFOX and chemoradiation before planned TME results in tumor regression, a high rate of delivery of planned therapy, and a substantial rate of pathCRs, and offers a good platform for nonoperative management in select patients.