Original ArticleWeight stabilisation is associated with improved survival duration and quality of life in unresectable pancreatic cancer☆
Introduction
The wasting that frequently accompanies advanced cancers, especially pancreatic cancer, has been well described.1., 2. Efforts to reverse the weight loss process through nutrition intervention, however, have had limited success.3., 4. It has not been clear whether intensive nutrition intervention for patients with unresectable pancreatic cancer results in improved outcomes.
Pancreatic cancer is the fourth leading cause of cancer mortality in the USA with more than 28,000 deaths/year.5 The disease is more common in men, however gender differences in incidence have been narrowing over recent years.6 More than 80% of cases occur in the 60–80 year age group. Less than 20% of patients survive 1 year from diagnosis,7 which reflects the fact that most cases of pancreatic cancer are not suitable for potentially curative treatment.8 Medical care for unresectable pancreatic cancer focuses on the management of symptoms to improve quality of life (QoL).9., 10. It is not known, however, whether halting weight loss would lead to longer survival or improved QoL.
Weight loss has been shown to be a negative prognostic indicator for a range of cancers, but this is less clear in the case of pancreatic cancer1., 11., 12., 13. possibly due to the confounding effect of oedema and ascites on body weight measurement and the short survival time from diagnosis. Features that have been associated with poorer prognosis in studies of advanced pancreatic cancer include metastatic disease,11., 12., 14. the presence of an acute phase response,11 pain12 and poor performance status.15 Interactions have also been demonstrated between age, gender and survival duration.12
Pancreatic cancer is accompanied by a range of symptoms that can affect food intake or utilisation—pain, nausea, anorexia, early satiety and pancreatic insufficiency.7., 15., 16. Alterations in metabolic rate,17 proinflammatory catabolic cytokines18., 19. and novel cachectic factors such as proteolysis inducing factor and lipid mobilising factor20., 21., 22. have also been reported in weight-losing pancreatic cancer patients. The importance of including health-related QoL as an outcome measure for studies of patients with advanced cancer is known.23., 24., 25.
A prospective multicentre randomised double-blind controlled trial was recently conducted by the Cancer Cachexia Study Group comparing the efficacy of an n-3 fatty acid enriched oral supplement with that of an isonitrogenous isocaloric oral supplement in weight-losing pancreatic cancer patients.26 Intent to treat analysis showed no significant difference in weight change between the two groups after 8 weeks of supplementation. There was, however, a marked attenuation of weight loss in both groups. This stabilisation is at odds with the progressive weight loss usually found in patients with unresectable pancreatic cancer2 suggesting that intensive nutrition intervention, which included the use of protein and energy dense oral supplements, may have prevented ongoing weight loss for many patients.
The purpose of this study was (1) to examine whether this weight stabilisation was associated with improved survival and QoL, and (2) to identify determinants of weight stabilisation.
Section snippets
Subjects
An international, multicentre, randomised, double-blind trial, was conducted between January 1999 and January 2001, in which 200 weight-losing pancreatic cancer patients were randomised to receive 8 weeks of intensive nutrition intervention including a protein and energy dense oral supplement with or without n-3 fatty acids. The methods used in the trial have been described in detail elsewhere.26 Eligibility criteria included weight loss of at least 5% over the previous 6 months, expected
Characteristics of included and excluded patients
Of the 200 patients enrolled in the multicentre study, 107 were eligible for this secondary analysis. Ninety patients were excluded because weight data were not available at Week 8. Lack of weight data was usually due to disease progression or death. One patient was excluded because ascites or oedema was reported within 70 days of baseline, and two were excluded due to death within 70 days of baseline. Mean age was 66.9±8.9 years and 58% were male.
The patients who were included in the analysis
Discussion
This study showed that for weight-losing patients with unresectable pancreatic cancer, weight stabilisation was associated with improved survival duration and QoL. The absence of nausea and vomiting at baseline and female gender were independent determinants of weight stabilisation.
All patients had been losing weight at baseline, with a minimum of 5% weight loss a criterion for study entry. Weight loss became markedly attenuated, with the majority of patients (59%) in this subgroup losing no
Acknowledgements
Contributors: WD was the main author of the manuscript, initiated the post hoc analysis, and carried out the statistical analysis and interpretation. SA supervised the project, assisted in the statistical analysis, interpretation and writing of the manuscript. SC supervised the project, assisted in the statistical analysis, interpretation and writing of the manuscript. JB assisted in the statistical analysis, interpretation and writing of the manuscript.
We thank Dr. Diana Battistutta for
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The Cancer Cachexia Study was supported by Abbott Laboratories, Chicago, USA.