Palliative nutritional intervention in addition to cyclooxygenase and erythropoietin treatment for patients with malignant disease: Effects on survival, metabolism, and function

Abstract

BACKGROUND The role of nutrition in the palliative treatment of patients with malignancy‐related cachexia is unclear. The goal of the current study was to determine whether specialized, nutrition‐focused patient care could improve integrated whole‐body metabolism and functional outcome in unselected weight‐losing patients with malignant disease who were receiving systemic antiinflammatory (cyclooxygenase [COX]‐inhibitory) treatment along with erythropoietin (EPO) support. METHODS Three hundred nine patients with malignant disease who experienced progressive cachexia due to solid tumors (primarily gastrointestinal lesions) were randomized to receive a COX inhibitor (indomethacin, 50 mg twice daily) and EPO (15–40,000 units per week) along with specialized, nutrition‐focused patient care (oral nutritional support and home total parenteral nutrition [TPN]) provided on a patient‐by‐patient basis to attenuate inflammation, prevent anemia, and improve nutritional status. Control patients received the same indomethacin and EPO doses that study patients received without the added nutritional support. All patients were treated and followed until death. Biochemical assays (blood, liver, kidney, and thyroid), nutritional state assessment (food intake and body composition), and exercise testing with simultaneous measurement of whole‐body respiratory gas exchange before and during exercise were performed before the start of treatment and then at regular intervals during the treatment period (every 2–30 months after treatment initiation). Statistical analyses were performed on ‘intention‐to‐treat’ and ‘as‐treated’ bases. RESULTS Home TPN was provided to approximately 50% of the study patients without severe complications. Over the entire observation period, rhEPO prevented the development of anemia in both study patients and control patients. Intention‐to‐treat analysis revealed an improvement in energy balance for nutritionally supported patients (P < 0.03); no other significant differences in outcome between study patients and control patients were observed. As‐treated analysis demonstrated that patients receiving nutrition experienced prolonged survival (P < 0.01), which was accompanied by improved energy balance (P < 0.001), increasing body fat (P < 0.05), and a greater maximum exercise capacity (P < 0.04). A trend toward increased metabolic efficiency at maximum exercise (P < 0.06) for study patients relative to control patients also was observed. CONCLUSIONS The results of the current study strongly support that nutrition is a limiting factor influencing survival and that nutritional support protects integrated metabolism and metabolic function in patients with progressive cachexia secondary to malignant disease. Cancer 2004. © 2004 American Cancer Society.

A prospective longitudinal study of performance status, an inflammation-based score (GPS) and survival in patients with inoperable non-small-cell lung cancer

“…Of the initial 101 patients studied, only 38 were available for the follow-up assessment. This high attrition rate is consistent with previous longitudinal studies of advanced cancer patients Vigano et al, 2000;Lundholm et al, 2004). In the present study, at diagnosis, the GPS was superior to ECOG-ps in predicting survival.…”

A randomized phase II feasibility trial of a multimodal intervention for the management of cachexia in lung and pancreatic cancer

“…In particular, multimodal trials have been recommended; however, the majority of cachexia trials have used single agents in isolation, or have lacked a comparator arm 23, 24. Where multimodal trials have been done,25, 26, 27 these have examined two or more components, and whilst some findings have been encouraging, to date, there have been no randomised trials integrating all the components we consider to be appropriate and this has resulted in a failure to advance cachexia treatment 28. Our findings suggest that multimodal cachexia intervention is safe and feasible and support further examination of this approach to fully assess effects on weight and lean body mass in larger trials.…”

Body composition and time course changes in regional distribution of fat and lean tissue in unselected cancer patients on palliative care—Correlations with food intake, metabolism, exercise capacity, and hormones

“…11 Some patients (n ϭ 50 patients) received recombinant erythropoietin in addition to indomethacin when blood hemoglobin levels became subnormal (Ͻ 125 g/L), as described previously, 12 and additional patients (n ϭ 141 patients) had received special nutritional support care when their caloric intake became reduced below 90% of resting needs in addition to indomethacin and erythropoietin treatment. 13 None of our patients received radiochemo- …”

“…Among these 311 patients, we identified 132 cancer patients who had at least 2 and an average of 3 measurements of body composition during follow-up (range, 4 -62 months). These patients were used for analysis of longitudinal relations between metabolism, physiologic functioning, nutrition, and body composition in cancer patients on evidence-based palliation (systemic antiinflammatory treatment, 11 recombinant erythropoietin treatment, 12,14 and specialized nutritional support care 13 ). All patients had generalized malignancy (T4N1M1) with a solid tumor type for which efficient tumor treatment was not available.…”

“…10 Therefore, the objective of the current analysis was to assess time course changes in regional body fat and lean tissue compartments in relation to other alterations in cancer cachexia, such as systemic inflammation, 11 food intake, 7 exercise capacity, 12 whole body substrate oxidation, 2 and circulating levels of hormones of known importance in cachexia among unselected, weight losing cancer patients who are receiving palliative care. 13 …”