No abstract

Capecitabine and temozolomide (CAPTEM) have shown promising results in the treatment of neuroendocrine neoplasms (NEN). The aim of this study was to evaluate the outcome and role for CAPTEM in malignant neuroendocrine neoplasms. Data were obtained from NEN patients who received at least one cycle of CAPTEM between November 2010 and June 2018. The average number of cycles was 9.5. For analysis, 116 patients were included, of which 105 patients (91%) underwent prior treatment. Median progression free survival (PFS) and overall survival (OS) were 13 and 38 months, respectively. Overall response rate (ORR) was 21%. Disease control rate (DCR) was 73% in all patients. PFS, median OS, ORR, and DCR for pancreatic NENs (pNEN) vs. non-pNEN was 29 vs. 11 months, 35 vs. 38 months, 38% vs. 9%, and 77% vs. 71%, respectively. Patients with pNEN had a 50% lower hazard of disease progression compared to those with non-pNEN (adjusted Hazard Ratio: 0.498, p = 0.0100). A significant difference in PFS was found between Ki-67 < 3%, Ki-67 3–20%, Ki-67 > 20–54%, and Ki-67 ≥ 55% (29 vs. 12 vs. 7 vs. 5 months; p = 0.0287). Adverse events occurred in 74 patients (64%). Our results indicate that CAPTEM is associated with encouraging PFS, OS, and ORR data in patients with NENs.

Neuroendocrine tumors (NETs) of the lung are divided into 4 major types: small cell lung cancer (SCLC), large cell neuroendocrine carcinoma (LCNEC), atypical carcinoid (AC) or typical carcinoid (TC). Each classification has distinctly different treatment paradigms, making an accurate initial diagnosis essential. The inconsistent clinical presentation of this disease, however, makes this difficult. The objective of this manuscript is to detail the diagnosis and management of the well differentiated pulmonary carcinoid (PC) tumors. A multidisciplinary approach to work up and treatment should be utilized for each patient. A multimodal radiological work-up is used for diagnosis, with contrast enhanced CT predominantly utilized and functional imaging techniques. A definitive diagnosis is based on tissue findings. Surgical management remains the mainstay of therapy and can be curative. In those with advanced disease, medical treatments consist of somatostatin analog (SSA) therapy, targeted therapy, chemotherapy or peptide receptor radionuclide therapy. SSAs are the standard of care in those with metastatic NETs, using either Octreotide long acting repeatable (LAR) or lanreotide as reasonable options, despite a scarcity of prospective data in PCs. Targeted therapies consist of everolimus which is approved for use in PCs, with various studies showing mixed results with other targeted agents. Additionally, radionuclide therapy may be used and has been shown to increase survival and to reduce symptoms in some studies. Prospective trials are needed to determine other strategies that may be beneficial in PCs as well as sequencing of therapy. Successful diagnosis and optimal treatment relies on a multidisciplinary approach in patients with lung NETs. Clinical trials should be used in appropriate patients.

Poorly differentiated gastroenteropancreatic neuroendocrine carcinomas (GEPNECs) are a rare neoplasm with a bleak prognosis. Currently there are little prospective data available for optimal treatment. This review discusses the current available regimens and the future direction for the treatment of GEPNECs. Treatment plans for GEPNECs are often adapted from those devised for small cell lung cancer; however, differences in these malignancies exist, and GEPNECs require their own treatment paradigms. As such, current first‐line treatment for GEPNECs is platinum‐based chemotherapy with etoposide. Studies show that response rate and overall survival remain comparable between cisplatin and carboplatin versus etoposide and irinotecan; however, prognosis remains poor, and more efficacious therapy is needed to treat this malignancy. Additional first‐line and second‐line treatment options beyond platinum‐based chemotherapy have also been investigated and may offer further treatment options, but again with suboptimal outcomes. Recent U.S. Food and Drug Administration approval of peptide receptor radionuclide therapy in low‐ and intermediate‐grade neuroendocrine tumors may open the door for further research in its usefulness in GEPNECs. Additionally, the availability of checkpoint inhibitors lends promise to the treatment of GEPNECs. This review highlights the lack of large, prospective studies that focus on the treatment of GEPNECs. There is a need for randomized control trials to elucidate optimal treatment regimens specific to this malignancy. Implications for Practice There are limited data available for the treatment of poorly differentiated gastroenteropancreatic neuroendocrine carcinomas (GEPNECs) because of the rarity of this malignancy. Much of the treatment regimens used in practice today come from research in small cell lung cancer. Given the poor prognosis of GEPNECs, it is necessary to have treatment paradigms specific to this malignancy. The aim of this literature review is to summarize the available first‐ and second‐line GEPNEC therapy, outline future treatments, and highlight the vast gap in the literature.