Background: The capecitabine/temozolomide regimen has significant activity in advanced NETs. Concerns exist regarding risk of opportunistic infections and long-term myelotoxicity. Analysis of large patient cohorts is needed for evaluation of rare toxicities and for assessment of risk factors. Methods: Retrospective study of all patients with advanced neuroendocrine neoplasms seen at the Moffitt Cancer Center between 1/2008 and 6/2019 who received treatment with CAPTEM. Patients who initiated treatment at outside institutions were included if they were prescribed treatment at appropriate doses and if complete records were available. Results: 462 patients met eligibility criteria for evaluation: 210 (45%) females and 252 (55%) males with a median age of 59. Median starting doses of CAP and TEM were 658mg/m² and 180mg/m² respectively. Median duration on treatment was 8 months. 25% of patients required a dose reduction and 16% discontinued due to toxicity of any grade. Incidence of grade 4 thrombocytopenia was 7%: 10% in females and 5% in males (p = 0.02). 4 cases were complicated by bleeding (0.8%). Incidence of grade 4 neutropenia was 3%: 5% in females and 1% in males (p = 0.004). Incidence of grade 4 lymphopenia was 2%. Only one case (0.2%) of suspected PCP was observed in a patient taking corticosteroids. There were 5 cases of herpes zoster and no other opportunistic infections. 3 patients developed myelodysplastic or myeloproliferative disease, all of whom had also received prior PRRT with Lutetium-Dotatate. There were no acute treatment related deaths, although one patient died 2 months after a thrombocytopenic bleed. Conclusions: Severe myelotoxicity is rare, but risks of grade 4 thrombocytopenia and neutropenia are significantly increased in females compared to males. Gender-based dosing should be considered. While alkylating agents are often associated with MDS, there were no cases except among patients who also had received PRRT, a known risk factor. PCP is not a significant risk with this regimen in patients not concurrently on corticosteroids.