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PubMed1999

[Doxifluridine decreases serum levels of interleukin-6 in a cancer cachexia model].

Cancer cachexia is a common paraneoplastic syndrome in patients with advanced malignancies. However, the mechanisms of the development of cancer cachexia remain to be elucidated. Interleukin (IL)-6 is known to be involved in the development of cancer cachexia. The KPL-4 human breast cancer cell line, which was recently established in our laboratory, secretes IL-6 into the culture medium. Oral administration of doxifluridine (5'-DFUR, 60 mg/kg or 120 mg/kg) significantly inhibited the growth of KPL-4 tumors, reduced the tissue levels of IL-6, and alleviated body weight loss. Serum IL-6 levels were also lowered by 5'-DFUR in nude mice bearing KPL-4 tumors. Additionally, it is suggested that tumor necrosis factor (TNF)-alpha is involved in the cachexia induced by KPL-4 tumors. We suggest that 5'-DFUR suppresses cancer cachexia by lowering IL-6 levels in the tumor tissues and serum.

Animals↗
PubMed2000

Protein metabolism in the small intestine during cancer cachexia and chemotherapy in mice.

The impact of cancer cachexia and chemotherapy on small intestinal protein metabolism and its subsequent recovery was investigated. Cancer cachexia was induced in mice with colon 26 adenocarcinoma, which is a small and slow-growing tumor characteristic of the human condition, and can be cured with 100% efficacy using an experimental nitrosourea, cystemustine (C6H12ClN3O4S). Both healthy mice and tumor-bearing mice were given a single i.p. injection of cystemustine (20 mg/kg) 3 days after the onset of cachexia. Cancer cachexia led to a reduced in vivo rate of protein synthesis in the small intestine relative to healthy mice (-13 to -34%; P < 0.05), resulting in a 25% loss of protein mass (P < 0.05), and decreased villus width and crypt depth (P < 0.05). In treated mice, acute cytotoxicity of chemotherapy did not promote further wasting of small intestinal protein mass, nor did it result in further damage to intestinal morphology. In contrast, mucosal damage and a 17% reduction in small intestinal protein mass (P < 0.05) were evident in healthy mice treated with cystemustine, suggesting that the effects of chemotherapy on the small intestine in a state of cancer cachexia are not additive, which was an unexpected finding. Complete and rapid recovery of small intestinal protein mass in cured mice resulted from an increase in the rate of protein synthesis compared with healthy mice (23-34%; P < 0.05). Northern hybridizations of mRNA encoding components of the major proteolytic systems suggested that proteolysis may not have mediated intestinal wasting or recovery. A major clinical goal should be to design methods to improve small intestinal protein metabolism before the initiation of chemotherapy.

Adenocarcinoma↗
PubMed2001

[Cytokines in experimental cancer cachexia].

OBJECTIVE: To investigate the relationship between cytokine IL-6, IL-1, TNF-alpha and experimental cancer cachexia as well as observe the effect of indomethacin on the cachectic mice. METHODS: T739 mice bearing lung adenocarcinoma LA795 were used as murine tumor cachexia model. In this experiment, serum IL-6, IL-1, TNF-alpha, glucose, protein and triglyceride levels and body weight in different stages of cancer cachexia were monitored. Thirty-two mice were randomized into four groups for comparison, with eight mice in each group: no tumor (NTB) group, tumor without treatment (NT) group, tumor with normal saline (NST) group and tumor with indomethacin (INDT) group. For the last group, intraperitoneal infusion of indothacin 1 microgram/gm was given once every day for six days starting from the 14 th day of tumor implantation. RESULTS: Compared with the NTB group, the NT group showed higher serum of IL-6, IL-1, TNF-alpha and lower total protein, triglyceride and glucose (P < 0.01). After treatment with indomethacin, the INDT mice gave higher serum glucose, protein and lipid levels. Meanwhile, the serum level of IL-6, TNF-alpha and IL-1 in the INDT group was found to be significantly low in comparison with the NST group. CONCLUSION: (1) IL-6, IL-1 and TNF-alpha appear to be involved in experimental cancer cachexia. (2) The positive effects of indomethacin by inhibiting the growth of these cytokines indicate that indomethacin is able to improve the condition of cancer cachexia.

Adenocarcinoma↗
PubMed2003

Increased plasma ghrelin level in lung cancer cachexia.

PURPOSE: Ghrelin, a novel growth hormone-releasing peptide,has been shown to cause a positive energy balance by stimulating food intake and inducing adiposity. We sought to investigate the pathophysiology of ghrelin in cachexia associated with lung cancer. EXPERIMENTAL DESIGN: Plasma ghrelin level was measured in 43 patients with lung cancer and 21 control subjects. Patients with lung cancer were divided into two groups: patients with cachexia (n = 21) and those without cachexia (n = 22). RESULTS: Plasma ghrelin level did not significantly differ between all patients with lung cancer and controls (157 +/- 10 versus 132 +/- 8 fmol/ml, P = 0.1). However, plasma ghrelin level was significantly higher in patients with cachexia than in those without cachexia (180 +/- 17 versus 135 +/- 10 fmol/ml, P = 0.011). Furthermore, plasma ghrelin level increased significantly in patients with decreased food intake after chemotherapy (from 136 +/- 11 fmol/ml to 170 +/- 16 fmol/ml on day 8, 179 +/- 20 fmol/ml on day 21 after start of chemotherapy), although plasma ghrelin level did not significantly change in those without decreased food intake. CONCLUSIONS: Baseline plasma ghrelin level was elevated in cachectic patients with lung cancer, and follow-up plasma ghrelin level increased in patients with anorexia after chemotherapy. Considering the positive energy effects induced by ghrelin, increased ghrelin may represent a compensatory mechanism under catabolic-anabolic imbalance in cachectic patients with lung cancer.

Aged↗
PubMed2005

MC4 receptor antagonists: a potential treatment for cachexia.

Cachexia (involuntary weight loss) is a devastating syndrome associated with many chronic diseases including cancer, and heart, lung, kidney and liver failure. There are currently no effective treatments capable of reversing the loss of lean body mass that is believed to be a major contributor to morbidity and mortality in these chronic diseases. Recent findings strongly indicate that blockade of central melanocortin signaling through the MC4 receptor subtype attenuates cachexia. This review summarizes the evidence supporting the role of MC4 receptors in cachexia, and highlights the progress achieved in the development of small-molecule MC4 antagonists, which have recently proved to be effective in animal models of cachexia. MC4 antagonists are an attractive therapeutic approach for cachexia that may ameliorate the loss of lean body mass in cachectic patients.

Animals↗
PubMed2004

[Molecular mechanisms of cancer cachexia].

Molecular mechanisms of cancer cachexia. Cancer cachexia is a complex, multifactorial syndrome characterised by a critical weight loss, anorexia, asthenia and anaemia. Most of the patients with advanced cancer suffer from cancer cachexia. The cachectic state is closely associated with progressive expansion of the tumour and leads to a malnutrition status due to the induction of anorexia and decreased food intake. In addition, the competition for nutrients between the tumour and the host leads to malnutrition state, too, which promotes severe metabolic disturbances in the host, including hypermetabolism which leads to an increased energetic inefficiency. Although, the search for the cachectic factors has a long history, we are still far away from knowing the complete answer. The main aim of the present paper is to summarise the different catabolic mediators involved in cancer cachexia. Better understanding of the pathomechanism of cancer cachexia can lead to the discovery of new, effective strategies of the therapy for the future.

Acute-Phase Proteins↗
PubMed2006

[Feeding-related disorders in medicine, with special reference to cancer anorexia-cachexia syndrome].

Cachexia is among the most debilitating and life-threatening aspects of cancer. Associated with anorexia, fat and muscle tissue wasting, psychological distress, and a lower quality of life, cachexia arises from a complex interaction between the cancer and the host. This process results from a failure of the adaptive feeding response seen in simple starvation and includes cytokine production, release of lipid-mobilizing and proteolysis-inducing factors, and alterations in intermediary metabolism. Cytokines play a pivotal role in long-term inhibition of feeding by mimicking the hypothalamic effect of excessive negative feedback signaling from leptin, a hormone secreted by adipose tissue, which is an integral component of the homeostatic loop of body weight regulation. The two major options for pharmacological therapy have been either progestational agents or corticosteroids. However, knowledge of the mechanisms of cancer anorexia-cachexia syndrome continues to lead to effective therapeutic interventions for several aspects of the syndrome. These include antiserotonergic drugs, gastroprokinetic agents, branched-chain amino acids, eicosapentanoic acid, cannabinoids, melatonin, and thalidomide, all of which act on the feeding-regulatory circuitry to increase appetite and inhibit tumor-derived catabolic factors to antagonize tissue wasting and/or host cytokine release. The outcomes of drug studies in cancer cachexia should focus on the symptomatic and quality-of-life advantages rather than simply on nutritional end points, since the survival of cachexia cancer patients may be limited to weeks or months due to the incurable nature of the underlying malignancy. As weight loss shortens the survival time of cancer patients and decreases their performance status, effective therapy would extend patient survival and improve quality of life.

Adipose Tissue↗
PubMed1991

Leucine kinetics in patients with benign disease, non-weight-losing cancer, and cancer cachexia: studies at the whole-body and tissue level and the response to nutritional support.

We have performed intraoperative isotopic infusions of carbon 14-labeled leucine in 65 patients to define the abnormalities in protein metabolism at both the whole-body and tissue level in patients with weight-losing and non-weight-losing cancer. Eighteen patients had benign disease, 26 had non-weight-losing cancer, and 21 had cancer cachexia. Samples of plasma and expired breath were taken to determine rates of whole-body protein synthesis (WBPS), whole-body protein catabolism (WBPC), net protein catabolism, and albumin fractional synthetic rates. Tissue samples were taken to determine the fractional synthetic rates (FSR) of protein in muscle, liver, cancer, and the tissue in which the cancer arose. In addition, in 14 patients the effect of nutritional support on protein metabolism was assessed. In all parameters examined we were unable to detect any significant differences between patients with no cancer and the patients with non-weight-losing cancer. In contrast, patients with cancer cachexia had a significant elevation (p less than 0.005) in WBPC compared with the other two groups. WBPS was also elevated (to a lesser extent) in the patients with cancer cachexia, and the rate of net protein catabolism was increased significantly (p less than 0.05). Patients with cancer cachexia also had significantly higher values of FSR of protein in muscle (p less than 0.05), liver (p less than 0.05), and albumin (p less than 0.01) compared with the other two groups. In addition, the protein FSR in the cancer rose progressively when the values for the primary cancer were compared with those for nodal and systemic metastases. Further, although nutritional support resulted in an increase in host muscle protein synthesis (p less than 0.04), there was no promotion of FSR of protein in cancer. We conclude that patients with cancer cachexia are actively losing protein as a result of an increase in WBPC that is only partially compensated for by an increase in WBPS. There are compensatory increases in protein synthesis in muscle and liver, but these increases in host protein synthesis are insufficient to keep pace with the combined effect of the accelerated rate of protein synthesis in the cancer per se and the accelerated rate of net protein catabolism at the whole-body level. In response to nutritional support, there is a significant increase in the muscle protein synthesis, but we could not demonstrate any increase in cancer protein synthesis.

Adult↗
PubMed1995

Purification and characterization of a lipid-mobilizing factor associated with cachexia-inducing tumors in mice and humans.

A scheme is described for the purification of a lipid-mobilizing factor from a cachexia-inducing murine tumor (MAC16) using a combination of ion exchange (Mono Q), exclusion (Superose), and hydrophobic (C8) chromatography. This process yields an active material with an apparent molecular weight of 24,000 with an overall purification of 3,500 from the tumor homogenate and representing 0.005% of the total protein present. The material tends to aggregate to high molecular mass, is acidic (pI < 4), and displays heterogeneity of charge as evidenced by a broad elution profile on ion exchange and exclusion chromatography and multiple peaks on hydrophobic columns. The purified material was heat and alkali (pH 10.4) labile and activity could be completely inhibited by sulfatase, suggesting that the negative charge could arise from sulfate residues. There was no evidence that the material possessed triglyceride lipase activity. Animals transplanted with the MAC16 tumor and with a delayed weight loss contained in their serum antibodies that recognized a M(r) 24,000 band on Western blots. This material copurified with the lipid-mobilizing factor. Such antibodies were not present in the serum of mice transplanted with the MAC13 tumor, which does not induce cachexia, suggesting that the antibodies were directed to the induction of cachexia rather than the tumor itself. Urine from patients with cancer cachexia also contained a lipid-mobilizing factor which adhered to DEAE-cellulose and gave an apparent M(r) of 24,000 by exclusion chromatography. Western blotting using serum from MAC16 tumor-bearing animals showed the presence of a band of M(r) 24,000 in such fractions, which was not detected using serum from mice bearing the MAC13 tumor. This band was not present in Western blots of urine from normal subjects. The fact that serum from mice bearing the MAC16 tumor can detect the human lipid-mobilizing activity suggests a high degree of structural similarity between the two and raises the possibility that cachexia in humans may be caused by the same species as in the mouse.

Animals↗
PubMed1993

Death in conditions of cachexia: the price for the dialysis treatment of the elderly?

Death in conditions of cachexia is increasing in potential dialysis patients, as treated cohorts are aging, the mean age of new patients increased and access to treatment is unlimited. The present study analyzes the clinical features of 417 deaths in conditions of cachexia recorded in 1981 to 1990 in the Dialysis and Transplantation Registry of a northern Italian region, Piedmont (about 4,400,000 inhabitants, 20 dialysis centers; 4,734 patients on file at December 31, 1990; yearly information on 100% of the cases). Death in conditions of cachexia increased from 105 cases in the first four years taken into account (1981 to 1984), to 107 in the last two years (1989 to 1990). Prevalence is higher in the elderly (85% of the death over age 60). Most patients (90.5%) were at high clinical risk. To assess whether the frequency of this diagnosis reflected the wide acceptance of elderly patients for dialysis and was a marked of vascular disease, a specific inquiry was conducted about 107 cachectic deaths recorded from 1989 to 1990: 82.5% of the patients had diffused vascular disease, 11.5% were already cachectic when dialysis was initiated, and 66% were in cachexia at least six months before death. Since mean age of patients dying in condition of cachexia increased from 68.8 in the period of 1981 to 1984 to 70.3 years in 1989 to 1990, and mean time on dialysis from 2.8 years in 1981 to 1984 to 70.3 years in 1989 to 1990, the higher prevalence is not likely to be due to lack of care of elderly patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Catabolic factors in cancer cachexia.

A lipid mobilizing factor has been purified from a cachexia-inducing mouse colon adenocarcinoma (MAC16) using a combination of ion exchange (Mono Q), exclusion (Superose) and reverse phase hydrophobic chromatography. The purification process led to a 3,500-fold increase in the specific activity. Serum from mice bearing the MAC16 tumour contained antibodies reactive with fractions containing lipid mobilizing activity and detectable as a 24 kDa immunoreactive band on Western blotting. Serum from mice transplanted with a related tumour, MAC13, not producing cachexia, did not contain antibodies. A similar immunoreactive band was detectable in the urine of patients with cancer cachexia, but was absent from the urine of normal subjects. A monoclonal antibody produced by fusion of splenocytes from mice bearing the MAC16 tumour with mouse Balb/c myeloma cells attenuated the development of cachexia in mice transplanted with the MAC16 tumour and inhibited tumour growth. These results suggest that the M(r) 24 kDa antigen may be important in tumour growth and cachexia.

Adenocarcinoma↗
PubMed1997

Prevention of adenocarcinoma colon 26-induced cachexia by interleukin 10 gene transfer.

A s.c. injection of a mouse colon adenocarcinoma cell line, colon 26 clone 20, induced cachexia, as evidenced by progressive weight loss and severe hypoglycemia. Several lines of evidence indicate that a pro-inflammatory cytokine, interleukin 6 (IL-6), plays a major role, albeit partially, in the establishment of cachexia in this model. Because IL-10 can potentially inhibit the production of pro-inflammatory cytokines including IL-6, we evaluated the effects of IL-10 gene transfer on the establishment of cachexia. IL-6 transcript was detected at tumor sites of mice inoculated with parental or control vector transfectant cells, and serum IL-6 levels were markedly increased in these mice. The injection of parental cells into IL-6-deficient mice induced cachexia with elevated serum IL-6 levels comparable to wild-type mice, indicating that tumor cells are a major source of IL-6. The inoculation of IL-10-transfectant cells kept IL-10 mRNA expression at tumor sites and induced the elevation in serum IL-10 levels without affecting the growth rates of colon 26 cells both in vitro and in vivo. However, the implantation with IL-10-transfectant cells reduced the expression of IL-6 mRNA at the tumor sites and the elevation in serum IL-6 levels. Concomitantly, mice inoculated with IL-10-transfectant cells did not exhibit progressive weight loss, a reduction in food intake, or severe hypoglycemia, which was observed in mice inoculated with parental or control vector-transfectant cells. Collectively, these results suggest that IL-10 gene transfer prevented the occurrence of cachexia with a concomitant inhibition of IL-6 production at the tumor sites.

Animals↗
PubMedDate not supplied

Effect of FR143430, a novel cytokine suppressive agent, on adenocarcinoma colon26-induced cachexia in mice.

Cancer cachexia, characterized by weight loss and progressive tissue wasting, has been postulated to be mediated by cytokines. In this study the effect of FR143430, (2-(4-fluorophenyl)-4, 5, 6, 7-tetrahydro-3-(4-pyridyl)pyrazolo[1, 5-a]pyrimidine monohydrochloride), an inhibitor of Interleukin-1 and Tumor necrosis factor-a (TNF- a), on adenocarcinoma colon26-induced cachexia was investigated in mice. Tumor growth was not affected. Nevertheless, treatment with FR143430 (0.1 to lmg) into the tumor resulted in the attenuation of the reduction in body weight, food intake, epididymal fat and carcass weight, the decrease in the circulating levels of triglyceride and glucose, and the increase in the circulating levels of total cholesterol, non esterified free fatty acid (NEFA) and total protein, which were induced by the presence of the tumor. However, oral treatment with FR143430 failed to show an inhibitory effect on cachexia induction. Overall, this study demonstrated that the cachexia induced by colon26 was alleviated by the injection of FR143430 into the tumor in sufficient quantity, without any effect on tumor growth, suggesting the potential utility of cytokine suppressive agents e for the treatment of cancer cachexia.

Animals↗
PubMed2005

Serum carnitine levels in patients with tumoral cachexia.

BACKGROUND: Cachexia is a serious complication of many cancers that is common in cancer and AIDS patients. However, the key factors and mechanisms involved in the development of cachexia are not yet understood. There is little data currently available regarding carnitine metabolism in patients with neoplasm and cachexia. METHODS: Forty-six neoplastic patients with different localizations of their primary disease gave signed, informed consent before enrolling in the present study. They underwent routine laboratory investigation, including examination of the levels of the various forms of carnitine present in serum (i.e., long-chain acylcarnitine, short-chain acylcarnitine, soluble acid acylcarnitine, free carnitine, and total carnitine). These values were compared with those found in 30 cancer patients in good nutritional status as well as with those of 30 healthy control subjects. RESULTS: In the comparison of serum plasma carnitine of cachectic patients versus controls, the difference in free carnitine was - 8.20 micromol/L (p=0.000); the difference in short-chain acylcarnitine - 2.60 micromol/L (p=0.029); the difference in soluble acid carnitine - 10.80 micromol/L (p=0.000); the difference in long-chain acylcarnitine - 0.40 micromol/L (p=0.036); and the difference in total carnitine -11.20 micromol/L (p=0.000). In the comparison of serum plasma carnitine of cachectic versus neoplastic patients in good nutritional status, the difference in free carnitine was -5.80 micromol/L (p=0.006); the difference in soluble acid carnitine - 7.20 micromol/L (p=0.000); and the difference in total carnitine - 7.50 micromol/L (p=0.000). CONCLUSION: Our study showed that, in the multifactorial pathogenesis of cachexia, the low serum levels of carnitine in terminal neoplastic patients, which are due to a decreased dietary intake as well as to an impaired endogenous synthesis of this substance, could play an important role. These low serum carnitine levels may also contribute to the development of cachexia in cancer patients.

Journal Article↗
PubMed1999

The role of cytokines in cancer cachexia.

A large number of observations point towards cytokines, polypeptides released mainly by immune cells, as the molecules responsible for the metabolic derangements associated with cancer-bearing states. Indeed, these alterations lead to a pathological state known as cancer cachexia which is, unfortunately, one of the worst effects of malignancy, accounting for nearly a third of cancer deaths. It is characterized by weight loss together with anorexia, weakness, anemia, and asthenia. The complications associated with the appearance of the cachectic syndrome affect both the physiological and biochemical balance of the patient and have effects on the efficiency of the anticancer treatment, resulting in a considerably decreased survival time. At the metabolic level, cachexia is associated with loss of skeletal muscle protein together with a depletion of body lipid stores. The cachectic patient, in addition to having practically no adipose tissue, is basically subject to an important muscle wastage manifested as an excessive nitrogen loss. The metabolic changes are partially mediated by alterations in circulating hormone concentrations (insulin, glucagon, and glucocorticoids in particular) or in their effectiveness. The present study reviews the involvement of different cytokines in the metabolic and physiological alterations associated with tumor burden and cachexia. Among these cytokines, some can be considered as procachectic (such as tumor necrosis factor-alpha), while others having opposite effects can be named as anticachectic cytokines. It is the balance between these two cytokine types that finally seems to have a key role in cancer cachexia.

Cachexia↗
PubMed1994

Growth hormone, insulin, and somatostatin therapy of cancer cachexia.

BACKGROUND: Cancer cachexia is associated with a decreased insulin:glucagon ratio. The authors hypothesized that the decrease in this anabolic hormone index is largely responsible for the progressive catabolism characteristic of cancer cachexia. Previous studies of insulin therapy alone in treating cancer cachexia have yielded limited success due to insulin-induced hypoglycemia and subsequent glucagon secretion. The current study was performed to determine the effect of combined hormone therapy (growth hormone, insulin, and somatostatin) on tumor growth, metastasis, and host metabolism. METHODS: Twenty-four female Lewis/Wistar rats (175-200 g) were subcutaneously inoculated on the flank with the MAC-33 tumor, a spontaneously metastasizing mammary adenocarcinoma. Thirty days after tumor implantation, animals were randomized to receive combined hormone therapy or saline (control) injections. Hormone therapy consisted of recombinant growth hormone (1000 U/kg/day intraperitoneally [IP]), somatostatin analogue (SMS 201-995; 150 micrograms/kg twice daily IP) and NPH humulin insulin (5 U/kg twice daily subcutaneously). RESULTS: Triple hormone therapy with growth hormone, insulin, and somatostatin significantly increased host carcass weight (211 +/- 4 g versus 179 +/- 6 g; P < 0.01) and decreased tumor:carcass ratio (0.25 +/- 0.03 versus 0.35 +/- 0.05; P < 0.01). Hamstring muscle weight and protein content were significantly increased and tumor cellular protein content was decreased in animals receiving triple hormone therapy. A significant decrease in S-phase tumor cell cycle kinetics occurred in hormone-treated versus control animals. CONCLUSIONS: Thus, combined therapy of growth hormone, insulin, and somatostatin selectively supports host anabolism and inhibits tumor growth kinetics. Combined hormone therapy specifically improves skeletal muscle protein content and reduces tumor protein incorporation. This innovative metabolic therapy for cancer cachexia may be useful in the future to prevent the progressive catabolism present in the tumor-bearing host.

Adenocarcinoma↗
PubMed1995

Mechanisms mediating cancer cachexia.

BACKGROUND: Cancer cachexia encompasses a wide range of metabolic, hormonal, and cytokine-related abnormalities that result in a wasting syndrome possibly accounting for up to 30% of cancer-related deaths. METHODS: A literature search was performed to review those pathways of metabolic interference involved in cancer cachexia. RESULTS: An elevated basal metabolic rate and increased energy expenditure combined with systemic catabolism of muscle and adipose tissue are the predominant manifestations of the metabolic and physiologic perturbations noted in this pathologic state. CONCLUSIONS: To date, although some of the cachexia-related metabolic abnormalities have been elucidated, there has been little success in relation to therapeutic manipulation of these pathways. This review evaluates current knowledge relating to cancer cachexia and cautions against generalizations concerning treatment regimens.

Animals↗
PubMed2005

Megestrol acetate for the treatment of anorexia-cachexia syndrome.

BACKGROUND: Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993 MA was approved by the USA's Federal Drug Administration for the treatment of anorexia, cachexia, or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown, and its effectiveness for anorexia and cachexia in neoplastic and AIDS patients is under investigation. OBJECTIVES: To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and other underlying pathologies. SEARCH STRATEGY: Studies were sought thorough an extensive search of the electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search was carried out on October 2002. SELECTION CRITERIA: Studies were included in the review if they assessed megestrol acetate compared to placebo or other drug treatments in randomized controlled trials of patients with a clinical diagnosis of anorexia-cachexia related to cancer, AIDS or another underlying pathology. DATA COLLECTION AND ANALYSIS: Data extraction was conducted by two independent authors, and methodological quality evaluated. Quantitative analyses were performed using appetite and quality of life as a dichotomous variable, and weight gain was analysed as continuous and dichotomous variables. Studies with more than 50% of patients lost to follow-up were excluded from the analysis. MAIN RESULTS: Thirty trials met the inclusion criteria (4123 patients). Twenty-one trials compared MA at different doses with placebo; four compared different doses of MA versus other drugs; two compared MA with other drugs and placebo; and three compared different doses of MA. For all patient conditions, meta-analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer patients. Analysing quality of life, clinical and statistical heterogeneity was found and discussed. There was insufficient information to define the optimal dose of MA. AUTHORS' CONCLUSIONS: This review demonstrates that MA improves appetite and weight gain in patients with cancer. No overall conclusion about quality of life (QOL) could be drawn due to heterogeneity. The small number of patients, methodological shortcomings and poor reporting have not allowed us to recommend megestrol acetate in AIDS patients or with other underlying pathologies.

Acquired Immunodeficiency Syndrome↗