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The aim of the study was to analyse the prevalence and characteristics of secondary diabetes induced by 5-fluorouracil (5-FU) based chemotherapy in non-diabetic patients with colorectal cancer (CRC).A total of 422 consecutive CRC patients who received 5-FU-based chemotherapy were retrospectively analysed. Fasting plasma glucose (FPG) levels were determined before each cycle of chemotherapy during active treatment and regular follow-up. The prevalence and characteristics of secondary hyperglycaemia were investigated, with special focus on the clinical outcome.Among the 422 CRC patients, 60 had pre-existing hyperglycaemia. In the remaining 362 with normal FPG levels before chemotherapy, 42 (11.6%) and 41 (11.3%) patients developed diabetes and impaired fasting glucose during the study period. Among the 42 secondary diabetic patients, 22 (52.4%) received anti-diabetes drug therapy, in 7 (16.7%) cases the FPG level returned to normal without any active intervention, and 13 (30.9%) cases received diet control and physiotherapy. Thirty-one (8.6%) patients developed diabetes. Based on the Common Terminology Criteria for Adverse Events, an adverse event over Grade 3 occurred in seven cases during follow-up. Diabetes-related adverse events had a serious negative impact on chemotherapy in six cases. Diabetes-related death occurred in three patients.Secondary diabetes associated with 5-FU-based chemotherapy occurs in around 10% of CRC patients, with a significant negative impact on treatment and clinical outcome. 5-FU-related diabetes should be regarded as a common side effect of 5-FU treatment.