The Effect of 5-Fluorouracil Chemotherapy on Energy Metabolism, Body Composition and Quality of Life in Patients With Colorectal Liver Metastases

Maguire, Roma (2001) The Effect of 5-Fluorouracil Chemotherapy on Energy Metabolism, Body Composition and Quality of Life in Patients With Colorectal Liver Metastases. MSc(R) thesis, University of Glasgow.

Abstract

Chemotherapy for metastatic colorectal cancer has been used for palliation for many years. During this time 5-FU has remained the single most effective anti-neoplastic agent in the treatment of colorectal cancers. Whilst many studies have assessed the safety and efficacy of chemotherapeutic regimens using response rate, toxicity profiles and quality of life, few studies have evaluated the effect of chemotherapy on the metabolic response of the host in particular energy balance, body composition and quality of life. The aim of this thesis was to examine the relationship between the systemic inflammatory response and body composition, dietary intake, resting energy expenditure, cytokine, hormone and protein metabolism in patients with colorectal liver metastases. In addition, the short and long term-effects of 5-FU based chemotherapy on the above measures of host metabolism, and quality of life in patients with colorectal liver metastases were assessed. In chapter 3, the host metabolic response of 5-FU based chemotherapy was assessed in patients with colorectal liver metastases. In 25 patients, haematological and biochemical parameters were measured before and after 6 cycles of chemotherapy. In a subset of 11 patients, energy balance, body composition, acute phase protein response and quality of life were measured. The results of this study indicate that, in patients with colorectal liver metastases receiving 5-FU based chemotherapy, a number of changes occur in both haematological and biochemical parameters. These changes were consistent with those commonly associated with chemotherapy. However, it was of interest that positive acute phase proteins such as fibrinogen fell in concentration during the course of the study while other proteins such as globulins did not. These results are consistent with 5-FU based chemotherapy resulting in a reduction of the systemic inflammatory response. Measured resting energy expenditure values were also noted to be higher than would be predicted whether expressed as kilocalories per day (median 113%) or per lean body mass derived from total body water (median 120%). There were no significant differences in energy intake or resting energy expenditure during the course of the study. Furthermore, in the present study where the majority of patients responded to treatment, there were no alterations in any of the body composition parameters. These results are therefore consistent with previous work which concluded, in lung cancer patients, that there was evidence for tumour induced hypermetabolism independent of changes in gross body composition, although the absolute increase in hypermetabolism is small. Global quality of life and Kamofsky performance status also did not change significantly during the course of the study. There was no change in physical function as measured by performance status and would suggest that the effect of 5-FU based chemotherapy, if any, on host energy metabolism is small. In summary, in patients with colorectal liver metastases, 5FU chemotherapy is 'fairly well' tolerated and is associated with a reduction in white blood cells, liver enzymes and acute phase proteins. In the sub-group there were no detectable effects on energy metabolism, body composition or quality of life. Tumour markers such as CEA have been demonstrated to be effective in alerting clinicians of the possibility of disease progression in patients with colorectal cancer. Furthermore, the presence and the magnitude of a systemic inflammatory response has also been reported to be associated with disease progression in patients with colorectal cancer. However, overall, few 'host markers' have been assessed in the development of disease progression in patients with colorectal cancer. Chapter four details a study of biochemical and haematological parameters in disease progression of patients with colorectal liver metastases receiving 5-FU based chemotherapy. Host factors that changed prior to CT defined progression were examined in 11 patients with colorectal liver metastases by comparing periods of 'responding disease' to 'progressive disease'. In addition, longitudinal assessment of patients prior to disease progression was assessed. On comparison of parameters during a period of 'responding' disease and 'progressive' disease, an increase in white cell count, neutrophil count and C-reactive protein on disease progression was observed. With regard to longitudinal assessment, white cell count, C-14 reactive protein and carcinoembryonic antigen were found to significantly change prior to CT-defined disease progression. Therefore, the results of this study may suggest that 12-14 weeks prior to CT-defmed disease progression there is tumour growth (as indicated by carcinoembryonic antigen levels) causing cell damage (as indicated by the transaminases) and necrosis, resulting in systemic inflammation, which in turn results in changes in liver protein production (C-reactive protein). (Abstract shortened by ProQuest.).

• Item Type: Thesis (MSc(R))
• Qualification Level: Masters
• Additional Information: Adviser: Donald C McMillan
• Keywords: Medicine, Oncology
• Date of Award: 2001
• Depositing User: Enlighten Team
• Unique ID: glathesis:2001-75759
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Nov 2019 18:15
• Last Modified: 19 Nov 2019 18:15
• URI: https://theses.gla.ac.uk/id/eprint/75759