This study provides one of the few longitudinal assessments of energy balance (body composition, REE, dietary intake) and the systemic inflammatory response (APPR) among advanced cancer patients receiving chemotherapy. However, the high dropout rate from the study illustrates the problem of making serial measurements in such seriously ill populations. Selection bias is introduced among the patients with NSCLC and melanoma because patients in whom a second measurement could be made were probably among the less seriously ill, but not apparently among those with metastatic breast cancer.
We did not show the anticipated fall in body weight over the course of chemotherapy among patients with NSCLC or melanoma, but there was a range of nutritional responses to chemotherapy within these groups. Patients with breast cancer did not change the overall weight, but had a propensity to gain fat and to lose FFM. The ability to meet or exceed energy requirements led to gains in weight and body fat among patients with NSCLC and metastatic breast cancer, but did not prevent loss of FFM in either group. The acute-phase response was linked to loss of weight and body fat among patients with NSCLC and loss of MAMC among patients with NSCLC and metastatic melanoma.
Studies of wasting and cancer have mainly been conducted among patients with gastrointestinal (GI) malignancies (Bosaeus et al, 2001
). We deliberately studied cancers that do not directly involve the GI tract to allow the effects of chemotherapy and the metabolic effect of the cancer being treated to be assessed. We have reconfirmed the variable change in weight among patients with NSCLC (Sarna et al, 1994
). Weight loss has previously been reported among patients with metastatic melanoma (Smit et al, 1983
). Weight maintenance in our patients may reflect less toxic chemotherapy regimens, and control of emesis. Loss of mid arm muscle alongside maintenance of FFM is these patients is consistent with previous reports of disproportionate loss of mid-arm muscle among cancer patients (Garrow, 1974
). Advanced breast cancer patients are considered to maintain good nutritional status despite the presence of widespread metastatic disease (Bozzetti et al, 1981
; Jardine et al, 1984
), although not all studies concur (DeWys et al, 1981
; Rowland-Payne et al, 1982
). Gains in fat and loss of FFM among patients with breast cancer in this study represent a deterioration of nutritional status during chemotherapy.
We have confirmed the presence of an elevated REE among patients with NSCLC (Staal-van den Brekel et al, 1997a
). Patients with both metastatic melanoma and metastatic breast cancer patients appeared to have a normal metabolic rate. There was a variable response in REE over the course of chemotherapy within each of the three groups. Previous reports have linked declines in REE with a response to chemotherapy (Jebb et al, 1994
), the reasons for the varied response among patients in the current study are unclear.
Contrary to expectations, energy intake increased over the course of chemotherapy in patients with melanoma and breast cancer. This may in part reflect an effect of the pre-dose chemotherapy steroids among the breast cancer patients. Whether steroids would continue to influence dietary intake 3 weeks post treatment is not known. Increases in dietary intake were particularly surprising in the patients with metastatic melanoma since the majority of this population received highly emetogenic decarbazine chemotherapy and did not receive steroids. Chemotherapy-associated increases in dietary intake have previously been reported in patients with early but not metastatic breast cancer (Heasman et al, 1985
). These increases are thought to be mediated by chemotherapy-associated hunger, an increased sense of well-being, or increased snacking to offset nausea (Grindel et al, 1989
We have confirmed the prevalence of an APPR among patients with NSCLC at 82% (Scott et al, 2003
). The APPR also occurred, but to a lesser extent, among patients with metastatic melanoma (37%) and metastatic breast cancer (44%). Patients taking anti-inflammatory medications, that is, steroids or ibuprofen, were included from the analysis as they still had an APPR. C-reactive protein would, if anything, be expected to be higher in these patients if they had not taken anti-inflammatory medications. Loss of weight and body fat was related to the level of CRP among patients with NSCLC, which confirms the findings from an earlier cross-sectional study (Scott et al, 1996
The ability to meet or exceed energy requirements led to gains in body fat but not FFM in patients with breast cancer and NSCLC. This is consistent with findings from earlier nutritional intervention studies (Evans et al, 1987
; Ovesen et al, 1993
). Gains in fat have not
been shown to confer advantages in terms of survival, chemotherapy-associated toxicity or quality of life among patients with NSCLC (Evans et al, 1987
). The declines in health-related quality of life alongside gains in body fat among patients with metastatic breast cancer in the present study suggest that gains in fat were not beneficial in this group. Gains in body fat may be particularly deleterious for women with breast cancer. Higher weight and stores of body fat are linked to poorer survival and prognosis among patients with breast cancer (Petrelli et al, 2002
; Borugian et al, 2003
), most likely mediated by the associated higher levels of oestrogen (Leenen et al, 1994
), insulin (Weinstock et al, 1998
) and bioavailable insulin-like growth factor-1 (IGF-1) (Nam et al, 1997
). Energy intake did not relate to changes in body fat among patients with metastatic melanoma in the present study. It is possible that the energy intake assessed 3 weeks after chemotherapy may not have reflected any acute decrease in energy intake in the immediate post-chemotherapy period. It also raises the possibility that changes in fat mass among patients with metastatic melanoma may be independent of energy balance and instead influenced by the presence of lipid-mobilising factors such as zinc-α
2 glycoprotein (Russell and Tisdale, 2002
; Bing et al, 2004
Preservation of FFM remains a major therapeutic challenge in the management of the cancer patients linked to improvements in functional capacity, prognosis (Tisdale, 2001
), and quality of life (Fearon et al, 2003
). Our study highlights that adequate dietary intake will not lead to gains in FFM during chemotherapy. Previous studies have linked loss of FFM (Simons et al, 1999
; Fearon et al, 2003
) to the presence of an inflammatory response in advanced cancer patients not receiving active treatment. We were unable to establish any links between CRP level and change in FFM in any of our advanced cancer groups over the course of chemotherapy. Loss of mid-arm muscle was linked to CRP among patients with NSCLC and metastatic melanoma, suggesting that loss of peripheral muscle mass at this site was linked to the inflammatory response. Total body potassium is considered by some to be a robust method of assessing lean body mass among cancer patients (Mcmillan et al, 2000
). We, however, failed to replicate a previous report that declines in TBK in cancer patients are linked to the APPR (Mcmillan et al, 1998
) (data not shown). A major distinction between the present and earlier reports that linked loss of FFM and TBK to the APPR is that our cancer patients were assessed throughout chemotherapy. Loss of FFM and TBK in patients receiving chemotherapy may be a function of the chemotherapy itself, which may limit protein synthesis (Herrmann et al, 1981
; Tayek and Chlebowski, 1992
), or may relate to the associated lower levels of hormones such as testosterone (Aaesebo et al, 1991
) and IGF-1 (Kajdaniuk and Marek, 2000
). The use of predose steroids among patients with NSCLC and breast cancer is unlikely to have led to loss of FFM in the doses used (Picado et al, 1990
). Declines in activity (secondary to chemotherapy associated fatigue) may be a specifically linked to loss of FFM among advanced cancer patients receiving chemotherapy. We did not assess physical activity, but preliminary studies among advanced cancer patients receiving chemotherapy have demonstrated home-based resistance and moderate exercise programmes to be efficacious in the preservation of FFM (Coleman et al, 2003
The possible limitation of assessment of FFM from skinfolds needs to be considered. No method of assessing lean (metabolically active tissue) is entirely satisfactory, particularly among cancer patients. All techniques (body potassium, dual emission X-ray absorptiometry, body water, body density, body impedance, in vitro
neutron activation analysis (IVNAA)) make assumptions about the relationship between the various body compartments and what is being measured (Burkinshaw, 1990
). FFM calculated from skinfold relies on a relationship with body density (Durnin and Womersley, 1974
). It is, however, the most widely used and the most robust of the techniques available. Hill et al (1978)
demonstrated a very close relationship between FFM and total body nitrogen (protein) measured using IVNAA. Mid upper arm muscle circumference is often used as an index of lean or fat-free body mass, but in wasting conditions tends to diminish faster than total body FFM (Garrow, 1974
). Total body potassium is considered to be an index of the functional body cell mass and muscle mass (Moore, 1980
). Previous studies have shown declines of TBK in patients receiving chemotherapy with a variety of tumours (Cohn et al, 1982
) and testicular cancer (Hyltander et al, 1991
). The reason for the lack of decline in TBK over the course of chemotherapy in patients in this study is unclear.
Small numbers of patients means that we were unable to assess whether response to chemotherapy influenced food intake, REE, body composition or APPR in each of the cancer groups. Response to chemotherapy has been linked to declines in REE, and preservation of FFM among patients with SCLC (Jebb et al, 1994
) and declines in APPR (Staal-van den Brekel et al, 1997b
). Some of the differences in body composition between the cancer groups may be in part due to gender effects (Harvie et al, 2003
), but we are unable to determine these gender effects from our analysis.
This study adds to the body of data that shows the varied nutritional response to chemotherapy even within individuals with the same tumour stage. Higher energy intakes lead to gains in fat among patients with advanced breast and lung cancer. Loss of FFM throughout chemotherapy, however, does not appear to be linked to inadequate intakes of energy or protein. Declines in MAMC were linked to the presence of an APPR. Preservation of FFM alongside chemotherapy treatments may not therefore be amenable to standard nutritional repletion. Further studies should investigate the potential benefits of anti-inflammatory medications (Fearon et al, 2003
) and exercise (Coleman et al, 2003
) on preservation of FFM among advanced cancer patients receiving chemotherapy.