Capecitabine and Temozolomide in Neuroendocrine Tumor of Unknown Primary

Abstract

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.

A Consensus-Developed Morphological Re-Evaluation of 196 High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms and Its Clinical Correlations

“…Peptide receptor radionuclide treatment in 60 GEP NET G3 patients resulted in PFS of 19 months and OS of 44 months [17]. Studies on temozolamide/ capecitabine treatment have reported RRs of 20-25% [22,23] and OS of 19 months [24], while everolimus led to PFS 6 months and OS 28 months in pancreatic NET G3 patients [25]. We found a PFS of only 5 months, and 28% progressed immediately on chemotherapy.…”

Capecitabine and temozolomide combination for treatment of high-grade, well-differentiated neuroendocrine tumour and poorly-differentiated neuroendocrine carcinoma — retrospective analysis

“…There are many retrospective and single-arm reports about CAPTEM use mainly in G1/G2 NETs of the pancreas [8,9,26,27], but data on G3 NENs is very limited. The confirmed efficacy of the CAPTEM regimen in G1/2 NETs encouraged attempts to treat G3 NETs in the second-line therapy [5] and in patients with Ki-67 >20% [9][10][11][12]. In the literature we found descriptions of outcomes of CAPTEM therapy in 18 patients with Ki-67 > 20% [9][10][11][12], and the treatment of NECs remains the domain of case reports [28].…”

“…There is no evidence from a randomised clinical trial on CAPTEM efficacy and safety. Data regarding the use of CAPTEM in G3 NENs is minimal, and neoplasms with Ki-67 > 20% into NETs and NECs were not differentiated in the literature reporting the use of CAPTEM [9][10][11][12]. Recently sunitinib was shown to be as effective for G3 NETs as for G1/2 NETs [13].…”

The optimal duration of capecitabine plus temozolomide in patients with well‐differentiated pancreatic NETs with or without maintenance therapy

“…Retrospective studies of CapTem treatment included NET from different origins and found that CapTem has limited efficacy in non‐PanNET 20,21 . Al‐Toubah at al 22 .…”

“…18,19 Retrospective studies of CapTem treatment included NET from different origins and found that CapTem has limited efficacy in non-PanNET. 20,21 Al-Toubah at al. 22 analysed 462 patients with NETs and showed that Patients with PanNET had the highest partial response rates and longest median PFS.…”