Original Paper
Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies?

https://doi.org/10.1016/S0959-8049(97)10090-9Get rights and content

Abstract

The aim of this study was to examine whether weight loss at presentation, in patients who were to receive chemotherapy for gastrointestinal carcinomas, influences outcome and whether nutritional intervention would be worthwhile. This study was a retrospective review of prospectively gathered data. The outcomes of patients with or without weight loss and treated for locally advanced or metastatic tumours of the oesophagus, stomach, pancreas, colon or rectum were compared. In 1555 such consecutive patients treated over a 6-year period, weight loss at presentation was reported more commonly by men than women (51 versus 44%, P = 0.01). Although patients with weight loss received lower chemotherapy doses initially, they developed more frequent and more severe dose limiting toxicity—specifically plantar-palmar syndrome (P < 0.0001) and stomatitis (P < 0.0001)—than patients without weight loss. Consequently, patients with weight loss on average received 1 month (18%) less treatment (P < 0.0001). Weight loss correlated with shorter failure-free (P < 0.0001, hazard ratio = 1.25) and overall survival (P < 0.0001, hazard ratio = 1.63), decreased response (P = 0.006), quality of life (P < 0.0001) and performance status (P < 0.0001). Patients who stopped losing weight had better overall survival (P = 0.0004). Weight loss at presentation was an independent prognostic variable (hazard ratio = 1.43). The poorer outcome from treatment in patients with weight loss appears to occur because they receive significantly less chemotherapy and develop more toxicity rather than any specifically reduced tumour responsiveness to treatment. These findings provide a rationale for attempting randomised nutritional intervention studies in these patients.

Introduction

Tangible progress has been made in treating gastrointestinal malignancies with chemotherapy in the last 10 years. Adjuvant chemotherapy using 5-fluorouracil (5-FU) regimens in selected patients with resected colorectal tumours is of proven benefit1, 2, 3and long-term control can be achieved in locally advanced oesophageal tumours using combination treatments including chemotherapy4, 5. Palliative chemotherapy for metastatic disease can improve survival and quality of life in patients with gastrointestinal cancers6, 7, 8, 9, 10, 11, 12. In addition, pre-operative or ‘neo-adjuvant’ chemotherapy may be effective at downstaging tumours, thereby increasing the opportunity for curative surgery6, 7, 8. If patients develop chemotherapy-induced toxicity, this may necessitate drug dose reduction6, 7, 8, 9, 10, 11, 12, 13, 14, 15to say nothing of the effect upon the patient. Therefore, any potential measures to reduce toxicity in both a curative and a palliative setting are of great importance.

In patients with gastrointestinal tumours, weight loss is a common feature and a frequent cause of patient concern. Weight loss at the time of initiating chemotherapy may indicate an aggressive tumour. However, many other factors may contribute to weight loss in patients with cancer, including a prolonged pre-operative illness, poor postoperative rehabilitation and pain, nausea, vomiting, diarrhoea, malabsorption and depression, all of which can be either iatrogenic or due to the malignancy.

Several studies have indicated that weight loss at presentation may be an independent prognostic variable of outcome16, 17, 18, but it has not been clearly shown why this might be the case. There are few data to support or refute the assertion that these are the patients with particularly aggressive disease. Another explanation may be that the presence of weight loss reduces the ability to respond to chemotherapy. Alternatively, weight loss may reduce performance status and, hence, less chemotherapy is tolerated or more toxicity develops. Or perhaps patients with weight loss receive less chemotherapy overall.

There are some 12 randomised studies in adults exploring the effects on response and survival of patients undergoing chemotherapy and receiving parenteral nutrition as an adjunct to chemotherapy19, 20, 21, 22and a handful using enteral nutrition23, 24. However, it is still quite unclear whether nutritional intervention to reverse weight loss in any patient undergoing chemotherapy is a useful strategy, or what the best method might be. The reason for the lack of progress is that many of these studies are seriously flawed as has been clearly pointed out in reviews19, 20and meta-analyses21, 22.

Our unit has been treating patients with tumours of the gastrointestinal tract with 5-fluorouracil-based chemotherapy for many years. The first aim of this study was to determine whether weight loss in our patients at presentation had an influence on the toxicity they suffered from chemotherapy and whether it affected their overall outcome. The second aim was to assess whether cessation of weight loss during treatment had any effect on outcome. Thirdly, we sought to establish whether our data supported the view that nutritional intervention in this group of patients might be worthwhile.

Section snippets

Patients

Every patient referred to the Gastrointestinal Oncology Unit at the Royal Marsden Hospital between April 1990 and March 1996 with histologically proven, locally advanced or metastatic tumours of the oesophagus, stomach, pancreas, colon or rectum and treated with chemotherapy was included in this study. Patients with adenocarcinoma of the oesophago-gastric junction were included within the gastric tumour group. Patients who received adjuvant chemotherapy were excluded. This retrospective study

Patient characteristics

This study included a total of 1555 patients: 179 with primary oesophageal squamous or adenocarcinoma, 433 with oesophago-gastric junction or gastric adenocarcinoma, 162 with pancreatic and 781 with colorectal adenocarcinoma. Men constituted 66% of the group. The median age of the cohort was 61 years (range 16–84 years). There was no difference in the median ages of patients presenting with or without weight loss. Weight loss was more common (P = 0.01) in men (51%) than in women (44%).

Discussion

The conundrum at issue is whether weight loss is simply an irreversible early marker of a patient who will fail to do well, or whether weight loss independently reduces the ability of some patients to be treated as effectively with chemotherapy. Our data provide some support for this second scenario. If weight loss per se reduces response to chemotherapy, simple, inexpensive, proven means of nutritional intervention are available and could be important adjuncts to treatment. However, the

Acknowledgements

Dr H.J.N. Andreyev is funded by a grant from the British Digestive Foundation.

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