Weight stabilisation is associated with improved survival duration and quality of life in unresectable pancreatic cancer

doi:10.1016/j.clnu.2003.07.001

Clinical Nutrition

Volume 23, Issue 2, April 2004, Pages 239-247

https://doi.org/10.1016/j.clnu.2003.07.001 Get rights and content

Abstract

Background & aims: Cancer-induced weight loss is associated with poor outcomes and is common in pancreatic cancer. The aims were to determine whether stabilising weight loss for patients with unresectable pancreatic cancer was associated with improved survival and quality of life (QoL) and to identify determinants of weight stabilisation.

Methods: A post hoc analysis was performed using data from 107 patients in a multicentre trial. Patients were categorised as weight losing (>1 kg lost) or weight stable (⩽1 kg lost) after an 8 week nutrition intervention period. Group survival duration (Kaplan Meier) and QoL (EORTC QLQ-C30) were compared. Predictors of weight stability were determined using logistic regression analysis.

Results: Patients with weight stabilisation survived longer from baseline (log rank test 5.53, P=0.019). They also reported higher QoL scores (P=0.037) and a greater mean energy intake (P<0.001) at Week 8 than those who continued to lose weight. The absence of nausea and vomiting (OR 6.5, P=0.010) and female gender (OR 5.2, P=0.020) were independent determinants of weight stabilisation.

Conclusions: Weight stabilisation over an 8 week period in weight-losing patients with unresectable pancreatic cancer was associated with improved survival duration and QoL.

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.

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Original ArticleWeight stabilisation is associated with improved survival duration and quality of life in unresectable pancreatic cancer☆

Abstract

Introduction

Section snippets

Subjects

Characteristics of included and excluded patients

Discussion

Acknowledgements

Am J Med

Surg Oncol Clin North Am

Hematol Oncol Clin North Am

Eur J Cancer

J Pain Symptom Manage

J Am Diet Assoc

J Am Diet Assoc

Am J Clin Nutr

Nutrition

Changes in nutritional status associated with unresectable pancreatic cancer

Br J Cancer

A randomized study of oral nutritional support versus ad lib nutritional intake during chemotherapy for advanced colorectal and non-small-cell lung cancer

J Clin Oncol

Effect of dietary counseling on food intake, body weight, response rate, survival, and quality of life in cancer patients undergoing chemotherapya prospective, randomized study

J Clin Oncol

Cancer statistics, 2001

CA Cancer J Clin

Pancreatic cancerstate-of-the-art care

CA Cancer J Clin

Current surgical therapy for carcinoma of the pancreas

J Clin Gastroenterol

Palliative and supportive care of patients with pancreatic cancer

Semin Oncol

Acute-phase protein response and survival duration of patients with pancreatic cancer

Cancer

Pooling of prognostic studies in cancer of the pancreatic head and periampullary regionthe triple-P study. Triple-P study group

Eur J Surg

Guidelines for the application of surgery and endoprostheses in the palliation of obstructive jaundice in advanced cancer of the pancreas

Ann Surg

Supportive nutritional management of the patient with pancreatic cancer

Oncology (Huntingt)

Contribution of anorexia and hypermetabolism to weight loss in anicteric patients with pancreatic cancer

Br J Surg

Cytokines, the acute-phase response, and resting energy expenditure in cachectic patients with pancreatic cancer

Ann Surg

Serum levels of tumor necrosis factor-alpha and nutritional status in pancreatic cancer patients

Anticancer Res

Original Article
Weight stabilisation is associated with improved survival duration and quality of life in unresectable pancreatic cancer☆