Metronomic chemotherapy in patients with advanced neuroendocrine tumors: A single‐center retrospective analysis

Abstract

Neuroendocrine tumors (NETs) are more commonly slow-growing, therefore patients often receive chronic systemic therapies for tumor growth control and preservation of quality of life. Metronomic chemotherapy (mCT) is in line with this goal as it leads to stabilization of tumor growth over time without severe systemic toxicity. This is a retrospective analysis of patients with metastatic NETs receiving metronomic capecitabine (mCAP) or temozolomide (mTEM), at a NET-referral center. The aims of the study were to explore activity and safety of mCT and relationships between some characteristics of the patient population and clinical outcomes. Among a total of 67 patients with metastatic well or moderately differentiated (W/M-D) NETs, mostly gastroenteropancreatic (GEP) and nonfunctioning, 1.2 years (95% CI: 0.8-1.8) median progression-free survival (mPFS), and 3.0 years (95% CI: 2.3-4.9) median overall survival (mOS) were observed. Disease control rate was 85%. Grade 3 adverse events occurred in 15% of patients in mCAP and 13% in mTEM, and were mostly hematological and gastrointestinal. At univariate and multivariate analysis none of the variables analyzed (treatment regimen, sex, age at diagnosis, site of primary tumor and metastases, number of previous mCT lines, baseline tumor status before mCT, Ki67 value) were significantly correlated to OS and PFS. Our retrospective study suggested that mCAP and mTEM can be active and well tolerated in patients with metastatic W/M-D NETs, irrespective of the primary site, site of metastases, line of treatment and baseline tumor status.

Metronomic Temozolomide (mTMZ) and Bevacizumab—The Safe and Effective Frontier for Treating Metastatic Neuroendocrine Tumors (NETs): A Single-Center Experience

“…Chan et al, for instance, reported on the effectiveness of a different therapeutic approach but did not provide a detailed breakdown by tumor grade or Ki-67 index, which is crucial for a nuanced understanding of treatment outcomes. Moreover, studies on the CAPTEM regimen, another recognized treatment for neuroendocrine tumors, present with a high degree of patient heterogeneity [16][17][18]20,[22][23][24]. This variability in patient profiles, encompassing a range of tumor grades and Ki-67 indices, adds complexity to any direct comparison with our results.…”

“…Although the progression-free survival (PFS) exhibited by bevacizumab mirrored that of interferon, bevacizumab displayed a superior response rate, extended time to treatment failure (TTF), and a reduced incidence of side effects like fatigue [15]. Capturing the tumor cycle in low proliferating (slow-growing) neuroendocrine tumors is of paramount importance, and daily, low-dose continuous chemotherapy regimens might be aptly suited for this purpose [16][17][18]. Variations in dosing have been observed in studies focused on the metronomic application of TMZ [16][17][18].…”

“…Capturing the tumor cycle in low proliferating (slow-growing) neuroendocrine tumors is of paramount importance, and daily, low-dose continuous chemotherapy regimens might be aptly suited for this purpose [16][17][18]. Variations in dosing have been observed in studies focused on the metronomic application of TMZ [16][17][18]. This drug's primary mechanism pivots around the inhibition of tumor angiogenesis by directly targeting endothelial cells in the tumor milieu and curtailing the mobilization of endothelial progenitor cells from the bone marrow [19].…”

“…Numerous studies have attested to its efficacy in treating neuroendocrine tumors, either as monotherapy or synergistically with other agents [17][18][19][20][21][22][23][24]. While a plethora of literature elucidates the efficacy of TMZ monotherapy or in tandem with capecitabine for metastatic neuroendocrine tumors [16][17][18]20,[22][23][24], only a handful have delved into the combination of TMZ and bevacizumab [21,25]. There also exists a case report highlighting the dramatic radiological and clinical response observed in a patient with metastatic neuroendocrine carcinoma.…”