Safety and efficacy of combining capecitabine and temozolomide (CAPTEM) to treat advanced neuroendocrine neoplasms

Abstract

Retrospective studies have suggested that capecitabine combined with temozolomide (CAPTEM) is effective for treating patients with advanced neuroendocrine neoplasms (NENs); however, the efficacy and safety of this regimen needs to be verified by high-quality evidence or results of randomized controlled trials.We carried out a meta-analysis to evaluate the safety and effectiveness of a CAPTEM protocol for patients with advanced NENs. Systematic electronic literature searches were conducted using PubMed, EMBASE, and the Cochrane Library, and among meeting abstracts of the American Society of Clinical Oncology, European Society for Medical Oncology, European Neuroendocrine Tumor Society, and North American Neuroendocrine Tumor Society, up to June 30, 2017. We selected studies describing CAPTEM regimens for treating advanced NENs and reported on tumor response and/or toxicities according to clear World Health Organization (WHO) grading of patients. Three reviewers independently and repeatedly identified studies, extracted data, and assessed the quality of the literature. A single-proportion meta-analysis was applied to included articles.Fifteen studies with a total of 384 individuals were included. Medium overall survival in most studies was more than 12 months, whereas medium progression-free survival was similar or slightly higher than that in studies using other treatment regimes. Disease control rate of CAPTEM administration for patients with NENs was 72.89% (95% confidence interval, 64.04–81.73%; I2 = 82.4%; P < .01). WHO grade 3 to 4 toxicities, such as thrombocytopenia (3.36%), neutropenia (0.69%), lymphopenia (0.65%), anemia (0.59%), mucositis (0.57%), fatigue (0.54%), diarrhea (0.49%), nausea (0.39%), and transaminase elevation (0.13%) were reported in the trials included.CAPTEM is effective and relatively safe for treating patients with advanced NENs.

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

“…To our knowledge, this is the first study documenting the efficacy and safety of the CAPTEM regimen in subgroups of patients with high Ki-67 index, divided into G3 NETs and NECs based on the WHO 2017 classification [1]. The median PFS for all patients of 7.1 months (95% CI: 3.27-15.3) was comparable to the range from 3.4 to 6.0 months reported in the recent metanalysis by Lu et al [29]. However, comparison of survival and response based on the Ki-67 level cut-off at 55% showed that results of the treatment were better in G3 NETs than in NECs.…”

Management of Gastrointestinal Neuroendocrine Tumors

“…148-150 Irinotecan/cisplatin (IP) and etoposide/cisplatin (EP) are the most common chemotherapy regimens for progressive advanced GI NETs. 151 Several studies have shown that capecitabine combined with temozolomide (CAPTEM), 152 bevacizumab, 153 5-fluorouracil, 154 and streptozotocin 155 can be also applied in unresectable GI NETs. Given the current level of evidence of cytotoxic chemotherapy, there remains much controversy about their use.…”

Temozolomide Is a Potential Therapeutic Tool for Patients With Metastatic Pheochromocytoma/Paraganglioma—Case Report and Review of the Literature

“…Capecitabine transforms into 5-FU in tumor tissues, and its metabolites can reduce the activity of MGMT, thus enhancing the effect of TMZ on DNA replication. Although the combination of TMZ and capecitabine is recommended for the treatment of pancreatic neuroendocrine neoplasms (29), it remains unknown whether the combination strategy works better than TMZ monotherapy in MPP patients. Prospective clinical trials are warranted.…”