Outcomes of Capecitabine and Temozolomide (CAPTEM) in Advanced Neuroendocrine Neoplasms (NENs)

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 Carcinomas with Atypical Proliferation Index and Clinical Behavior: A Systematic Review

“…While cisplatin or carboplatin-etoposide treatment regimens are a well-defined first-line therapeutic approach, based on therapy responses reported in SCLC studies [ 8 ], the combinations of 5-FU, leucovorin and irinotecan (FOLFIRI) and 5-FU, leucovorin and oxaliplatin (FOLFOX) have shown promising results in GEP-NECs as second line therapy [ 9 , 10 ]. Moreover, temozolomide and capecitabine may be used for patients who failed on first-line chemotherapy [ 11 , 12 ]. The peptide receptor radionuclide therapy (PRRT) also has been proposed as an alternative treatment approach for GEP-NECs [ 13 , 14 ], while immunotherapy is promising, but its effectiveness has not been demonstrated yet in GEP-NECs [ 15 ].…”

Somatostatinoma and Neurofibromatosis Type 1-A Case Report and Review of the Literature

“…The use of the CAPTEM regimen is associated with objective responses and promising survival outcomes in metastatic, well-differentiated, intermediate and high-grade NETs (two-year OS = 42%, median PFS = 10 months, median PFS = 17 months in patients who received CAPTEM in first line) [ 47 ]. More studies reported similar results regarding CAPTEM regimen in NEN, with significantly higher PFS, median OS, objective response rate and disease control rate in pNENs compared with non-pNENs [ 48 , 49 ]. Pancreatic NENs have a lower O (6)-methylguanine-DNA methyltransferase (MGMT) expression than non-pNENs, and this might be the rationale for a superior treatment response to CAPTEM regimen.…”

“…CAPTEM regimen is rarely associated with serious toxicities (grade 3 or 4 stratified by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade) and has low discontinuation rates, even in patients who follow the treatment for more than a year [ 48 ]. The ENETs guidelines currently recommend this regimen for patients with intermediate and high-grade NETs as a second line therapy [ 51 ].…”

How I treat neuroendocrine tumours

“… 32 In addition to these prospective data, there is evidence for the efficacy of CAPTEM at various sites of NEN, but documented activity seems to be highest in pancreatic and lung NET. 33–35 There are still unanswered questions including optimal sequencing and impact of the MGMT-methylation status as biomarker.…”