Safety and efficacy of combining capecitabine and temozolomide (CAPTEM) to treat advanced neuroendocrine neoplasms: A meta-analysis

Medicine (Baltimore). 2018 Oct;97(41):e12784. doi: 10.1097/MD.0000000000012784.


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%; I = 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.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Capecitabine / administration & dosage
  • Capecitabine / adverse effects
  • Capecitabine / therapeutic use*
  • Dacarbazine / administration & dosage
  • Dacarbazine / adverse effects
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neuroendocrine Tumors / drug therapy*
  • Observational Studies as Topic
  • Survival Analysis
  • Temozolomide


  • Capecitabine
  • Dacarbazine
  • Temozolomide