A double-blind, placebo-controlled randomized trial of creatine for the cancer anorexia/weight loss syndrome (N02C4): an Alliance trial.

BACKGROUND: Multiple pilot studies, including one in colorectal cancer patients, suggest that creatine, an amino acid derivative, augments muscle, improves strength, and thereby could palliate the cancer anorexia/weight loss syndrome. PATIENTS AND METHODS: In this randomized, double-blind, placebo-controlled trial, incurable patients with this syndrome were assigned creatine (20 g/day load×5 days followed by 2 g/day orally) versus identical placebo. Patients were weighed once a week for 1 month and then monthly. Patients were also assessed over 1 month for appetite and quality of life (validated questionnaires), fist grip strength, body composition (bioelectrical impedance), and adverse events. The primary endpoint was 10% or greater weight gain from baseline during the first month. RESULTS: Within this combined cohort of 263 evaluable patients (134 received creatine and 129 placebo), only 3 gained ≥10% of their baseline weight by 1 month: two creatine-treated and the other placebo-exposed (P = 1.00). Questionnaire data on appetite, quality of life, and activities of daily living showed no statistically significant differences between groups. Similarly, no statistically significant differences between groups were observed for fist-grip strength or body composition. Rates and severity of adverse events were comparable between groups. Finally, a median survival of 230 and 239 days were observed in the creatine and placebo groups, respectively (P = 0.70). CONCLUSION: Creatine, as prescribed in this trial, had no effect on the cancer anorexia/weight loss syndrome.

Risk of acute myeloid leukemia and myelodysplastic syndrome among older women receiving anthracycline-based adjuvant chemotherapy for breast cancer on Modern Cooperative Group Trials (Alliance A151511).

PURPOSE: We examined acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) events among 9679 women treated for breast cancer on four adjuvant Alliance for Clinical Trials in Oncology trials with >90 months of follow-up in order to better characterize the risk for AML/MDS in older patients receiving anthracyclines. METHODS: We used multivariable Cox regression to examine factors associated with AML/MDS, adjusting for age (≥65 vs. <65 years; separately for ≥70 vs. <70 years), race/ethnicity, insurance, performance status, and anthracycline receipt. We also examined the effect of cyclophosphamide, the interaction of anthracycline and age, and outcomes for those developing AML/MDS. RESULTS: On Cancer and Leukemia Group B (CALGB) 40101, 49907, 9344, and 9741, 7290 received anthracyclines; 15% were in the age ≥65 and 7% were ≥70. Overall, 47 patients developed AML/MDS (30 AML [0.3%], 17 MDS [0.2%]); 83% of events occurred within 5 years of study registration. Among those age ≥65 and ≥70, 0.8 and 1.0% developed AML/MDS (vs. 0.4% for age <65), respectively. In adjusted analyses, older age and anthracycline receipt were significantly associated with AML/MDS (adjusted hazard ratio [HR] for age ≥65 [vs. <65] = 3.13, 95% confidence interval [CI] 1.18-8.33; HR for anthracycline receipt [vs. no anthracycline] = 5.16, 95% CI 1.47-18.19). There was no interaction between age and anthracycline use. Deaths occurred in 70% of those developing AML/MDS. CONCLUSIONS: We observed an increased risk for AML/MDS for older patients and those receiving anthracyclines, though these events were rare. Our results help inform discussions surrounding anticipated toxicities of adjuvant chemotherapy in older patients.

A phase II study (ARCHER 1042) to evaluate prophylactic treatment of dacomitinib-induced dermatologic and gastrointestinal adverse events in advanced non-small-cell lung cancer.

BACKGROUND: ARCHER 1042, a randomized phase II trial, explored the impact of prophylactic treatment on select dermatologic adverse events of interest (SDAEI), diarrhea, and mucositis associated with dacomitinib, an oral irreversible pan-human epidermal growth factor receptor (HER) inhibitor, in development for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced NSCLC treated with dacomitinib were enrolled in two cohorts. Cohort I patients were randomized 1:1 to receive oral doxycycline or placebo (4 weeks). Cohort II patients received oral VSL#3 probiotic plus topical alclometasone. Primary end points for Cohorts I and II were incidence of all grade and grade ≥2 SDAEI in the first 8 weeks of treatment and quality of life (QoL) assessed by the Skindex-16 survey. Additional primary end points for Cohort II were incidence of all grade and grade ≥2 diarrhea and mucositis in the first 8 weeks of treatment; QoL regarding diarrhea and mucositis incidence was assessed by the modified-Oral Mucositis Daily Questionnaire. RESULTS: Cohort I randomized 114 evaluable patients: 56 in the doxycycline arm, 58 in the placebo arm. Cohort II enrolled 59 evaluable patients. Doxycycline significantly reduced the incidence of grade ≥2 SDAEI by 50% (P = 0.016) compared with placebo. The incidence of all grade SDAEI was lower with doxycycline than with placebo but did not reach statistical significance. Doxycycline was associated with less deterioration in QoL compared with placebo. Alclometasone was associated with less deterioration in QoL compared with placebo but did not statistically significantly reduce the incidence of all grade or grade ≥2 SDAEI. VSL#3 did not reduce the incidence of all grade or grade ≥2 diarrhea and did not impact mucositis scores. CONCLUSIONS: Doxycycline was effective as a prophylactic treatment for dacomitinib-induced grade ≥2 SDAEI. Both doxycycline and alclometasone reduced the negative impact in patient-reported dermatologic AEs. The probiotic was not effective for preventing diarrhea or mucositis.

Disease-free ovarian cancer patients report severe pain and fatigue over time: prospective quality of life assessment in a consecutive series.

UNLABELLED: objective: Among ovarian cancer patients, cancer treatment is aggressive and yet survival is often so limited; hence, this study sought to measure quality of life with the ultimate goal of identifying ways of improving it over the duration of these patients' lives. MATERIALS AND METHODS: The medical records of all ovarian cancer patients who received some/all of their initial chemotherapy at the Mayo Clinic in Rochester, Minnesota from late 2010 through 2012 were reviewed. Patient-reported quality of life was derived from the following ten-point linear analogue scale questions which had been administered to all patients: 1) How would you describe your degree of pain, on average? 2) How would you describe your level of fatigue, on average? 3) How would you describe your overall quality of life? Quality of life data were censored upon cancer recurrence. RESULTS: Among 59 eligible patients, the median cumulative interval during which quality of life was serially assessed was 1.15 years (range: three months, 3.2 years). Area under the curve for pain, fatigue, and global quality of life showed no statistically significant differences between patients treated with dose-dense chemotherapy with carboplatin/paclitaxel (n = 10) versus three-week chemotherapy with carboplatin/paclitaxel (n = 36) versus other (n = 13). Although pain, fatigue, and global quality of life improved over time, 35 of 59 (59%) patients reported grade 4 or worse pain during follow up, and 47 of 59 (80%) reported grade 4 or worse fatigue (higher scores denote worse pain or fatigue). After completion of cancer treatment, 30 (51%) described grade 4 or worse pain or fatigue. The most common pain site was the abdomen/pelvis, followed by the back, followed by the hands, feet, fingers, and toes. CONCLUSION: In ovarian cancer patients who remain cancer-free, severe pain and fatigue occur years after cancer treatment. Further research should focus on how best to address these symptoms.

Early recognition of malnutrition and cachexia in the cancer patient: a position paper of a European School of Oncology Task Force.

BACKGROUND: Weight loss and cachexia are common, reduce tolerance of cancer treatment and the likelihood of response, and independently predict poor outcome. METHODS: A group of experts met under the auspices of the European School of Oncology to review the literature and-on the basis of the limited evidence at present-make recommendations for malnutrition and cachexia management and future research. CONCLUSIONS: Our focus should move from end-stage wasting to supporting patients' nutritional and functional state throughout the increasingly complex and prolonged course of anti-cancer treatment. When inadequate nutrient intake predominates (malnutrition), this can be managed by conventional nutritional support. In the presence of systemic inflammation/altered metabolism (cachexia), a multi-modal approach including novel therapeutic agents is required. For all patients, oncologists should consider three supportive care issues: ensuring sufficient energy and protein intake, maintaining physical activity to maintain muscle mass and (if present) reducing systemic inflammation. The results of phase II/III trials based on novel drug targets (e.g. cytokines, ghrelin receptor, androgen receptor, myostatin) are expected in the next 2 years. If effective therapies emerge, early detection of malnutrition and cachexia will be increasingly important in the hope that timely intervention can improve both patient-centered and oncology outcomes.

Ostomies in rectal cancer patients: what is their psychosocial impact?

The resection of a low-lying rectal cancer can lead to the creation of an ostomy to discharge fecal material. In view of this reconfiguration of anatomy and life-changing modification of daily bodily functions, it is not surprising that a rapidly growing literature has examined ostomy patients' psychosocial challenges. The current study was designed (1) to systematically review the published literature on these psychosocial challenges and (2) to explore, in a single-institution setting, whether medical oncologists appear to acknowledge the existence of an ostomy during their post-operative evaluations of rectal cancer patients. This systematic review identified that social isolation, sleep deprivation; financial concerns; sexual inhibition; and other such issues are common among patients. Surprisingly, however, in our review of 66 consecutive rectal cancer patients, in 17%, the ostomy was not mentioned at all in the medical record during the first medical oncology visit; and, in one patient, it was never mentioned at all during months of adjuvant chemotherapy. Even in the setting of ostomy complications, the ostomy was not always mentioned. This study underscores the major psychosocial issues cancer patients confront after an ostomy and suggests that healthcare providers of all disciplines should work to remain sensitive to such issues.

Overall survival and self-reported fatigue in patients with esophageal cancer.

PURPOSE: A prospective cohort study was conducted to analyze whether self-reported fatigue predicts overall survival in patients with esophageal cancer. METHODS: Patients enrolled in the Mayo Clinic Esophageal Adenocarcinoma and Barrett's Esophagus Registry between September 2001 and January 2009 who completed a baseline quality of life instrument were eligible for evaluation. The fatigue component was scored on a 0-10 scale, with 0 as extreme fatigue. Patients were categorized as having a decreased energy level if they reported a score of ≤ 5. Fatigue scores ≥ 6 reflect normal levels of energy. RESULTS: Data from a total of 659 enrolled patients were analyzed. A total of 392 (59 %) and 267 (41 %) patients reported decreased and normal energy, respectively. Univariate analysis indicates patients with normal energy had improved 5-year survival compared to patients with decreased energy (37 vs 28 %, hazard ratio (HR) 0.74, p = 0.006). Among the patients with locally advanced disease, the same relationship was seen (28 vs 17 %, HR = 0.67, p = 0.003); this remained significant on multivariate analysis (HR = 0.71, p = 0.015). CONCLUSIONS: A decreased energy level is associated with poor survival in patients with esophageal cancer. Thus, patients with high levels of fatigue should be referred for psychological support and be considered for therapy aimed at amelioration of fatigue symptoms.

Bone pain from granulocyte colony stimulating factor: does clinical trial sponsorship by a pharmaceutical company influence its reporting?

It is alleged that pharmaceutical companies sometimes unfairly present clinical trial results. To our knowledge, studies have not explored whether such alleged unfair reporting also occurs in the testing of palliative care agents in cancer patients, a particularly vulnerable group. Therefore, a systematic search was conducted to retrieve all published, prospective clinical trials that used granulocyte colony stimulating factor starting in 2003. Because granulocyte colony stimulating factor can cause severe bone pain - a concerning but historically under-reported symptom in cancer patients - this symptom was assessed to determine whether differences in reporting occurred based on pharmaceutical company-sponsorship. A total of 239 published clinical trials met the present study's eligibility criteria and were retrievable. Within this entire group of studies, 65 (27%) were pharmaceutical company-sponsored, and only 31 (13%) reported on bone pain. However, pharmaceutical company-sponsored trials reported on bone pain at a higher rate compared with other studies: 23% versus 9% (P= 0.005), and this conclusion did not change after adjusting for dose, use of the slow release formulation and year of publication. The reporting of adverse events from cancer symptom control and palliative care interventions should be improved - especially in trials not sponsored by pharmaceutical companies.

A phase II study of cetuximab and radiation in elderly and/or poor performance status patients with locally advanced non-small-cell lung cancer (N0422).

BACKGROUND: Non-small-cell lung cancer (NSCLC) is a disease of the elderly. Seeking a tolerable but effective regimen, we tested cetuximab + radiation in elderly and/or poor performance status patients with locally advanced NSCLC. PATIENTS AND METHODS: Older patients [≥ 65 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2] or younger patients (performance status of 2) received cetuximab 400 mg/m(2) i.v. on day 1 followed by weekly cetuximab 250 mg/m(2) i.v. with concomitant radiation of 6000 cGy in 30 fractions. The primary end point was the percentage who lived 11+ months. RESULTS: This 57-patient cohort had a median age (range) of 77 years (60-87), and 12 (21%) had a performance status of 2. Forty of 57 (70%) lived 11+ months, thus exceeding the anticipated survival rate of 50%. The median survival was 15.1 months [95% confidence interval (CI) 13.1-19.3 months], and the median time to cancer progression was 7.2 months (95% CI 5.8-8.6 months). No treatment-related deaths occurred, but 31 patients experienced grade 3+ adverse events, most commonly fatigue, anorexia, dyspnea, rash, and dysphagia, each of which occurred in <10% of patients. CONCLUSION: This combination merits further study in this group of patients.

Non-traumatic vertebral fractures in patients with locally advanced esophageal cancer: a previously unreported, unrecognized problem.

Recent studies suggest cancer therapy may compromise bone integrity. What is the rate of vertebral fractures among patients who have received trimodality therapy (radiation, chemotherapy, and surgery) for locally advanced esophageal cancer? This single-institution, retrospective study attempted to answer this question, focusing on 337 patients who had received trimodality therapy for locally advanced esophageal cancer between 1996 and 2005. Reports of serial radiographs were reviewed to identify vertebral fractures. Duration of follow-up was gathered for all esophageal cancer patients with the intention of calculating fracture incidence rates. Fracture-related symptoms, types of intervention and fracture recurrence were also gleaned from the clinical records. First-time fractures were identified in 47 patients, and 45 of these were new since the cancer diagnosis. Thus, the first-time fracture incidence rate from the time of cancer diagnosis was 12 fractures per 100 patient years. The median time from cancer diagnosis to fracture was 9 months. Fifteen (33%) patients were symptomatic. Acknowledging that a retrospective study can inadvertently result in information omission, we report that pain medications were started in only seven patients (16%), and osteoporosis medication in only six (13%). Two patients were hospitalized, and two underwent vertebroplasty. The median survival after fracture diagnosis was 36 months. This report describes a seemingly high fracture incidence rate that requires confirmation. If confirmed, future studies should focus on identifying risk factors and optimal strategies for the prevention and treatment of vertebral fractures in patients with esophageal cancer.

Curing patients with locally advanced esophageal cancer: an update on multimodality therapy.

Combining different treatment modalities--such as surgery, radiation, and chemotherapy--is often utilized to treat patients with locally advanced esophageal cancer. However, it remains controversial how best to combine these modalities to provide patients with the greatest chance of cure. This review discusses recent studies in this field and outlines promising versus less promising therapeutic strategies.

The proteolysis-inducing factor: in search of its clinical relevance in patients with metastatic gastric/esophageal cancer.

The proteolysis-inducing factor is a putative mediator of cancer-associated weight loss. The goal of this study was to examine for the first time: (i) its prevalence in patients with metastatic gastric/esophageal cancer; and (ii) whether it possibly correlated with weight loss and anorexia and whether it predicted tumor response and patient survival. This study recruited 41 patients as part of a phase II therapeutic, chemotherapy protocol for patients with metastatic gastric/esophageal cancer. Patient eligibility criteria were designed to select a group of patients who would tolerate treatment with the drugs capecitabine and oxaliplatin. Urine for assaying the proteolysis-inducing factor was obtained at registration and then 6 weeks later. Patients completed the FACT-E questionnaire every 6 weeks and had their weights checked at the same interval. Patients were followed prospectively for tumor response and patient survival. Twenty-three (56%) patients had the proteolysis-inducing factor in their urine at registration, and 18 (64%) had it at 6 weeks. There was no statistically significant correlation between the presence of the proteolysis-inducing factor and weight loss or between its presence and anorexia. Moreover, there was no evidence that the presence of the proteolysis-inducing factor in urine was able to predict tumor response or patient survival. The proteolysis-inducing factor in urine does not appear to be tied to weight loss, anorexia, tumor response, or patient survival in the clinical setting of metastatic gastric/esophageal cancer.

Docetaxel and capecitabine in patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction: a phase II study from the North Central Cancer Treatment Group.

BACKGROUND: Previous studies suggest that the combination of docetaxel and capecitabine are worthy of further testing in patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. We therefore undertook this phase II study to test this combination in a multi-institutional, first-line clinical trial. PATIENTS AND METHODS: Forty-four eligible patients with histologic or cytologic confirmation of the above malignancy were recruited. The cohort had Eastern Cooperative Oncology Group performance scores of 0, 1 and 2 in 59%, 39% and 2% of patients, respectively. Median age was 57 years (range 32-77 years). Adequate organ function was a requirement for study entry. All patients were prescribed docetaxel 75 mg/m2 intravenously on day 1 and capecitabine 825 mg/m2 orally twice a day on days 1-14 of a 21-day cycle. RESULTS: The tumor response rate was 39% [95% confidence interval (CI) 23% to 55%]. There were two complete responses and the rest were partial. Median survival was 9.4 months (95% CI 6.3-10.7 months) and median time-to-tumor progression was 4.2 months (95% CI 3.6-5.6 months). There was one treatment-related death from a myocardial infarction and dysrhythmia. Commonly occurring grade 3 adverse events included neutropenia (11 patients), infection (five patients), constipation (three patients), thrombosis (three patients), dyspnea (three patients) and hand-foot syndrome (three patients). In addition, 24/45 patients developed grade 4 neutropenia. CONCLUSIONS: The regimen docetaxel and capecitabine shows activity in patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. This regimen merits further study.

Oxaliplatin and capecitabine in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia: a phase II study from the North Central Cancer Treatment Group.

PURPOSE: The synergic combination of oxaliplatin and capecitabine has demonstrated activity against various gastrointestinal cancers, including colon cancer. We therefore undertook this phase II study to test this first-line combination in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia. PATIENTS AND METHODS: Forty-three patients with histologic or cytologic confirmation of the above malignancy were recruited. The cohort had Eastern Cooperative Oncology Group performance statuses of 0, 1 and 2 in 47%, 51%, and 2%, respectively. Median age was 61 years (range 32-80). All had adequate organ function. Initially, patients were prescribed 130 mg/m2 intravenously on day 1 and capecitabine 1000 mg/m2 orally twice a day, on days 1-14 of a 21-day cycle. Four treatment-related deaths in the first 24 patients led to a reduction in capecitabine to 850 mg/m2 orally twice a day, days 1-14, for the remainder of the cohort. RESULTS: The tumor response rate was 35% [95% confidence intervals (CI) 23% to 50%]. All responses were partial; seven of 24 occurred before the capecitabine dose reduction, and eight of 19 after. Median time to tumor progression was 4 months (95% CI 3.1-4.6), and median survival 6.4 months (95% CI 4.6-10). To date, there have been 36 deaths. Four were treatment-related (one infection, two myocardial infarctions, one respiratory failure), and all occurred before the capecitabine dose reduction. Notable grade 4 events from the entire cohort included diarrhea (two patients), vomiting (three), dyspnea (one), thrombosis (two) and anorexia (two). Grade 3 events included nausea (12 patients), diarrhea (12), fatigue (10), abdominal pain (seven), vomiting (six), dyspnea (six), hypokalemia (six), dehydration (five), hypokalemia (five) and infection (four). CONCLUSIONS: Oxaliplatin and capecitabine in combination demonstrates activity in metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia. The lower dose (capecitabine 850 mg/m2 orally twice a day, days 1-14, and oxaliplatin 130 mg/m2 intravenously on day 1) yielded an acceptable toxicity profile and merits further study.

Investigating four 'myths' surrounding dysphagia in patients with metastatic esophageal cancer. A multi-institutional study from the North Central Cancer Treatment Group.

Eighty-five to 95% of esophageal cancer patients suffer dysphagia. Yet, few studies have focused on this symptom, and four 'myths' persist: (i) dysphagia cannot be measured; (ii) chemotherapy cannot palliate it; (iii) dysphagia predicts a poor prognosis; (iv) dysphagia is associated with a frustratingly insatiable appetite. Forty-four patients with metastatic esophageal cancer participated in this quality of life/translational component of a previously reported clinical trial. All were monitored for chemotherapy efficacy and toxicity and completed questionnaires on dysphagia and appetite at baseline and every 6 weeks. The appetite hormones, leptin and neuropeptide y, were also assessed. Forty-five per cent of patients could easily swallow solid foods; all others had varying dysphagia, thus enabling exploration of these four 'myths.' First, a single-item visual analog scale (Swallowing Scale), demonstrated excellent agreement with a previously validated questionnaire (81% at baseline), thus reminding us that dysphagia is measurable. Second, chemotherapy was associated with a trend towards improved dysphagia (P = 0.059). Third, dysphagia did not predict tumor response or survival. Fourth, dysphagia was not associated with appetite, leptin or neuropeptide y. This study helps to dispel these four 'myths' and underscores the need for further quality of life research on dysphagia.

Environmental tobacco smoke exposure in women with lung cancer.

BACKGROUND: Investigations on environmental tobacco smoke (ETS) exposure that include source intensity, childhood exposure, and association with histologic subtypes among never smoking lung cancer cases are limited. We report the patterns of ETS exposure history in a clinical cohort of women with newly diagnosed lung cancer. METHODS: From 1997 to 2001, 810 women with lung cancer were interviewed to obtain data including the source, intensity, and duration of ETS exposure. In this descriptive study, relationships between smoking history, ETS exposure, and lung cancer histologic subtypes were analyzed. RESULTS: Among the 810 patients, 773 (95.4%) reported personal smoking or ETS exposure including 170 of 207 (82%) never smokers. Among the never smokers with a history of ETS exposure, the mean years of exposure were 27 from a smoking spouse, 19 from parents, and 15 from co-workers. For each major subtype of lung cancer (adenocarcinoma, squamous cell, unclassified non-small cell lung cancer, small cell, or carcinoids) among never smokers, 75-100% of patients had ETS exposure. Trends for adenocarcinoma, squamous, and small cell carcinoma are statistically significant using the Cochran-Armitage Test for Trend (P<0.001) among never smokers without ETS exposure, never smokers with ETS exposure, former smokers, and current smokers. CONCLUSIONS: Over 95% of women with lung cancer in our study were exposed to tobacco smoke through a personal smoking history or ETS. The cumulative amount of tobacco smoke exposure may be significantly underestimated if only personal smoking history is considered. Our results add to the public health implications of exposure to tobacco smoke and highlight the importance of eliminating tobacco smoking in public and private settings.

An update: cancer-associated anorexia as a treatment target.

Loss of appetite is pervasive among patients with advanced cancer. Cancer patients cite it as one of their most troubling symptoms. To date, however, palliative options remain limited. Megestrol acetate and dexamethasone provide only modest relief. Novel agents such as thalidomide, adenosine triphosphate, and other cytokine inhibitors merit further investigation.

Neuropeptide Y, leptin, and cholecystokinin 8 in patients with advanced cancer and anorexia: a North Central Cancer Treatment Group exploratory investigation.

BACKGROUND: Anorexia is a noxious symptom, and over half of patients with advanced cancer experience it. Neuropeptide Y (NPY), leptin, and cholecystokinin 8 (CCK8) have been implicated. METHODS: This exploratory study 1) compared circulating concentrations of NPY and leptin between anorectic cancer patients and historic controls and 2) explored whether NPY, leptin, or CCK8 may serve as correlates of anorexia severity. Cancer patients met predefined eligibility criteria: 1) weight loss > or = 2.3 kg over the preceding 2 months and/or a physician-estimated caloric intake of < 20 calories per kilogram of body weight per day and 2) patient acknowledgment that appetite or weight loss was an ongoing problem. RESULTS: Seventy-three cancer patients were studied, and > 90% reported a > or = 50% decline in appetite from baseline in the preceding 2 months. NPY levels were lower than control values: mean +/- standard deviation, 466 pg/mL +/- 161 pg/mL versus 560 pg/mL +/- 151 pg/mL, respectively (P = 0.004). Because a few (but not all) earlier studies suggested an age-related decline in NPY levels, a subgroup analysis was performed and found no age-adjusted difference in NPY levels between groups. Similarly, leptin concentrations were not different between groups. Significant correlations were not observed between anorexia severity and NPY, leptin, or CCK8 levels. CONCLUSIONS: There were no differences in leptin and CCK8 levels between anorectic cancer patients and historic controls. Circulating concentrations of NPY, leptin, and CCK8 did not correlate with anorexia severity. However, the current results suggest a need for further examination of NPY in cancer-associated anorexia.

Do patients with nonmetastatic non-small cell lung cancer demonstrate altered resting energy expenditure?

BACKGROUND: The cancer cachexia syndrome occurs in patients with non-small cell lung cancer (NSCLC) and includes elevated resting energy expenditure (REE). This increase in REE leads to weight loss, which in turn confers a poor prognosis. This study was undertaken to determine whether the cancer cachexia syndrome occurs in patients with nonmetastatic NSCLC. METHODS: In this case-control study, 18 patients with nonmetastatic NSCLC (stages IA to IIIB) were matched to healthy controls on age (+/- 5 years), gender, and body mass index (+/- 3 kg/m2). Only 4 cancer patients had experienced > 5% weight loss. Cancer patients and controls were compared on the basis of: (1) unadjusted REE, as measured by indirect calorimetry; (2) REE adjusted for lean body mass, as measured by dual x-ray absorptiometry; (3) REE adjusted for body cell mass, as measured by potassium-40 measurement; and (4) REE adjusted for total body water, as measured by tritiated water dilution. RESULTS: We observed no significant difference in unadjusted REE or in REE adjusted for total body water. However, with separate adjustments for lean body mass and body cell mass, cancer patients manifested an increase in REE: mean difference +/- standard error of the mean: 140+/-35 kcal/day (p = 0.001) and 173+/-65 kcal/day (p = 0.032), respectively. Further adjustment for weight loss yielded similarly significant results. CONCLUSIONS: These results suggest that the cancer cachexia syndrome occurs in patients with nonmetastatic NSCLC and raise the question of whether clinical trials that target cancer cachexia should be initiated before weight loss.