Aman Chauhan

The Role of Capecitabine/Temozolomide in Metastatic Neuroendocrine Tumors

BACKGROUND Neuroendocrine tumors (NETs) are commonly treated with multimodality therapy. The combination of capecitabine and temozolomide (CAPTEM) has been suggested as a treatment option for patients with metastatic NETs. We present our experience with CAPTEM. METHODS Data on NET patients who were placed on CAPTEM and received at least one cycle were obtained from a Velos eResearch database. Response rate was calculated by RECIST 1.1. Overall survival and progression-free survival (PFS) were calculated by the Kaplan-Meier survival method. RESULTS A total of 29 patients (17 male and 12 female) were included. Median age at CAPTEM initiation was 58 years (range: 26-77). Primary tumors included 9 small bowel (31%), 15 pancreas (52%), 3 lung (10%), and 2 rectum (7%). Median number of CAPTEM cycles was 8 (range: 1-55). Partial response occurred in 5 patients (5 of 29, 17%); 14 patients (14 of 29, 48%) had stable disease, and 10 patients (10 of 29, 34%) had progressive disease. A total of 3 (20%) and 5 (33%) pancreatic NETs experienced partial response and stable disease, respectively. A total of 2 (14%) and 9 (64%) nonpancreatic NETs experienced partial response and stable disease, respectively. Partial response was noted in 1 patient (13%) and stable disease in 5 patients (63%) with Ki-67 values of less than 2%. In patients with Ki-67 values of 2%-20%, partial response was noted in 3 (19%) and stable disease in 8 (50%). Partial response and stable disease were noted in 1 patient each (20%) with Ki-67 values greater than 20%. Median PFS was 12 months. Adverse reactions caused dose reductions in 24% of patients. CONCLUSION Although adverse reactions were experienced, most patients tolerated this regimen. CAPTEM should be considered as a reasonable treatment option for metastatic NET patients. IMPLICATIONS FOR PRACTICE The role of chemotherapy in neuroendocrine tumors has evolved in recent years. The results of this study suggest that the combination of capecitabine and temozolomide provides an adequate treatment option and may prolong survival in patients with a wide variety of metastatic neuroendocrine tumors. Although prospective data are needed, this research adds to the abundance of retrospective experience with this combination that appears to show that capecitabine and temozolomide could potentially be an option for patients with advanced neuroendocrine tumors who have progressed on standard treatment.

Management of pulmonary neuroendocrine tumors

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.

Ramucirumab: a Novel Anti-Angiogenic Agent in the Treatment of Metastatic Colorectal Cancer

Angiogenesis is a multistep process that plays a key role in cancer growth and metastases. It is mediated through multiple vascular endothelial growth factor receptors (VEGFRs) and their ligands. The expression of VEGFR-2 is upregulated in tumor endothelial cells, and it is considered to be the primary receptor driving malignant angiogenesis. Ramucirumab (IMC-1121B, LY3009806) is a fully human monoclonal antibody that directly binds to VEGFR-2 with high affinity and specificity. It is also the most recent addition to our armamentarium of anti-angiogenic drugs approved for the treatment of metastatic colorectal cancer (CRC). The aim of this review is to summarize the pre-clinical and clinical development of ramucirumab and discuss its place in the current treatment paradigm for metastatic CRC.

Global burden of neuroendocrine tumors and changing incidence in Kentucky

Background Neuroendocrine tumors (NETs) have a low incidence but relatively high prevalence. Over the last three decades, the incidence of NETs has risen 6-fold in the United States. We conducted an observational study to compare the incidence of NETs reported to the Kentucky Cancer Registry (KCR) versus that reported to Surveillance, Epidemiology, and End Results Program (SEER). We also provide a systematic review of the state of neuroendocrine tumors worldwide, and compare the available global and local published data. Methods KCR and SEER databases were queried for NET cases between 1995 and 2015. A detailed literature review of epidemiological data for various nations worldwide summarize epidemiological data from various countries. Results KCR recorded 6179 individuals with newly diagnosed NETs between 1995 and 2015. Between 1995-2012, the incidence of NETs in KCR increased from 3.1 to 7.1 per 100,000 cases, while it increased from 3.96 to 6.61 in the SEER database. The incidence rates in both KCR and SEER databases were linear. 90.57% were Caucasians with 54.74% females. 27.67% of the Kentucky population was from the Appalachian region. Patients aged 50-64 years had the highest prevalence (38%). Lung NET (30.60%) formed the bulk of cases, followed by small intestine (16.82%), rectum/anus (11.35%) and colon (9.71%). Conclusions NETs incidence between 1995 and 2015 show a linear increase in both KCR and SEER databases. Because of this increased incidence it is imperative for community oncologists to familiarize themselves with this entity, which until recently was under-studied and with few viable treatment options.

Capecitabine and Temozolomide in Neuroendocrine Tumor of Unknown Primary

Incidence of low grade well-differentiated neuroendocrine tumors (NET) is on the rise. The North American Neuroendocrine Tumor Society estimates that the United States has more than 150,000 gastroenteropancreatic NET patients. About 10% of metastatic NETs can be unknown primary, and due to their rarity, dedicated treatment algorithms and regimens are not defined. Combination of capecitabine and temozolomide (CAPTEM) is one of the systemic treatments used in gastroenteropancreatic NETs. We explored clinical activity of CAPTEM in NET of unknown primary. Methods. Retrospective review of NET of unknown primary managed at the University of Kentucky over the past five years (2012–2016). Result. 56 patients with NET of unknown primary were identified; 12 patients were treated with CAPTEM. Median progression-free survival on CAPTEM in grade II and grade III NET of unknown primary was 10.8 and 7 months, respectively. Six patients showed reduction in metastatic tumor volume at three-month CT scan. Three patients had stable disease and three patients showed disease progression at the first surveillance scan. Common side-effects were as follows: four patients developed grade II thrombocytopenia, three patients developed grade I lymphocytopenia, and two patients developed hand foot syndrome (grades I and III). Six patients developed grade I fatigue. Conclusion. CAPTEM should be considered for grades I and II NET of unknown primary, especially in the case of visceral crisis or bulky disease.