Comparison of Temozolomide-Capecitabine to 5-Fluorouracile-Dacarbazine in 247 Patients with Advanced Digestive Neuroendocrine Tumors Using Propensity Score Analyses

Abstract

Introduction: Although chemotherapy combining 5-fluorouracil (5FU)-dacarbazine (DTIC) or temozolomide (TEM)-capecitabine (CAP) is extensively used in patients with neuroendocrine tumors (NET), they were never compared. We compared their tolerance and efficacy in advanced NET. Methods: We evaluated the records of consecutive patients with pancreatic or small-intestine advanced NET who received 5FU-DTIC or TEM-CAP between July 2004 and December 2017 in 5 French centers. Tolerance, tumor response and progression-free survival (PFS) were compared. Factors associated with PFS were analyzed using Cox multivariate regression model. To reduce the confounding bias of the nonrandomized design, PFS was compared using propensity score analyses. Results: Ninety-four (5FU-DTIC) patients and 153 (TEM-CAP) patients were included. Pancreatic NET represented 82.3% of cases and 17.1, 61.8 and 10.9% of patients had G1, G2 or G3 NET respectively. Progression at baseline was reported in 92.7% of patients with available data. Grades 3–4 adverse events occurred in 24.7 and 8.5% of TEM-CAP and 5FU-DTIC patients respectively (p = 0.002). The overall response rate was 38.3 and 39.2% respectively (p = 0.596). Median PFS on raw analysis was similar to 5FU-DTIC and TEM-CAP (13.9 vs. 18.3 months, respectively p = 0.86). TEM-CAP was associated with an increased risk of progression on the raw multivariate analysis (hazard ratio [HR] 1.90, 95% CI [1.32–2.73], p = 0.001) and when adjusted on propensity score (HR 1.65, 95% CI [1.18–2.31], p = 0.004). Conclusion: PFS may be longer with 5FU-DTIC than TEM-CAP in patients with advanced NET. Although patients often prefer oral chemotherapy, 5FU-DTIC is a relevant alternative. A randomized comparison is needed to confirm these results.

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

“…Additionally, de Mestier and colleagues (2019) compared CAPTEM with 5-fluorouracil (5FU)-dacarbazine (DTIC) in 247 patients with NEN. It was found that PFS was similar between the two groups 13.9 vs. 18.3 months, p = 0.86) [31]. Parallel to Chatzellis' study, the majority of patients getting CAPTEM had a pNEN primary disease (82.3%), and only 27 patients with non-pNENs.…”

“…Parallel to Chatzellis' study, the majority of patients getting CAPTEM had a pNEN primary disease (82.3%), and only 27 patients with non-pNENs. In this study, the use of CAPTEM in pNET was associated with a significantly higher ORR, PFS, and OS when compared to patients with non-pNENs [30,31].…”

“…In the past year, recent studies have reported on the use of CAPTEM in advanced NEN [29][30][31][32][33]. Chatzellis et al (2019) conducted a retrospective analysis of CAPTEM in 79 patients, of which 30 patients (38%) had pNEN and 15 patients had GI NEN primary disease.…”

Carcinoid Heart Disease: How to Diagnose and Treat in 2020?

“…Papaxoinis et al 49 de Mestier et al 50 registered. Reoperation was required in 5.9%, renal dysfunction was observed in 3% of cases, biliary dysfunction-in 3.6%, and death-in 1.2%.…”

Critical appraisal of MGMT in digestive NET treated with alkylating agents

“…The most widely used chemotherapy regimens in PanNETs rely on alkylating agents, such as streptozotocin (STZ) (combined with 5-fluorouracil (5FU) or doxorubicin (Dilz et al 2015, Clewemar Antonodimitrakis et al 2016), dacarbazine (DTIC) (alone or combined with 5FU (Walter et al 2015, de Mestier et al 2019) and its oral prodrug temozolomide (TMZ) (alone or combined with capecitabine (CAP) (Koumarianou et al 2015, de Mestier et al 2020b. However, chemotherapy has been scarcely compared to other therapeutic options yet.…”