Improperness of Hydration for 5-FU Base Chemotherapy for Colorectal Cancer May Induce Hyperammonemic Encephalopathy

Background and Purpose. 5-fluorouracil (5-FU)-based chemotherapy for colorectal cancer has been used for many years. Complications associated with 5-FU based chemotherapy are not rare, but central neurological effects, including encephalopathy, are unusual. Here, we analyzed our experience with complications associated with chemotherapy of colorectal cancer with the intent of learning how we might decrease the risk of complications. Methods. We retrospectively reviewed the medical records of patients in our section of Taipei Tzu Chi hospital who had received adjuvant or neoadjuvant chemotherapy from 2010 to 2014 for the treatment of colorectal cancer. We compared and analyzed the patients’ clinical characteristics, pre-chemotherapy laboratory data, chemotherapy regimens, and complications. Results. Eighty patients received the FOLFOX6 regimen; 13 patients received the FOLFIRI regimen together with bevacizumab. Four cases of hyperammonemic encephalopathy occurred. All cases were in patients who had received 5-FU dissolved in a modest volume (500 ml) saline, whereas no cases occurred in patients who received 5-FU in 2000 ml saline. No statically significant differences in pre-chemotherapy laboratory data, body surface area, or chemotherapy dose between patients with encephalopathy and those without encephalopathy were identified. We also analyzed all cases in which the dose of chemotherapy was reduced for any reason.We found a trend towards dose reduction associated with the administration of the chemotherapeutic agents in limited amounts of saline and a BUN/ creatinine ratio ＞ 20. Conclusions.We conclude that the administration of 5-FU in a low volume of fluid increases the risk of hyperammonemic encephalopathy and probably the need to reduce the doses of chemotherapeutic agents. Chemotherapeutic regimens with 5-FU in 500 ml saline should be avoided, especially if the pre-chemotherapy BUN/creatinine ratio is greater than 20.