Mary B. Grosvenor

Symptoms potentially influencing weight loss in a cancer population. Correlations with primary site, nutritional status, and chemotherapy administration

A nutritional assessment including determination of symptoms potentially influencing weight loss was prospectively performed on 254 consecutive cancer patients with favorable performance scores (Eastern Cooperative Oncology Group [ECOG] level 0 to 2). Primary cancer sites included the following: non‐small cell lung (n = 93), colon (n = 50), prostate (n = 23), oropharyngeal (n = 18), breast (n = 15), gastrointestinal (n = 13), and other (n = 42). Thirty‐nine percent of patients had received no prior chemotherapy or radiation therapy. Common symptoms in the population were abdominal fullness (61%), taste change (46%), constipation (41%), mouth dryness (40%), nausea (39%), and vomiting (27%). Current caloric intake was surprisingly similar in 170 patients with weight loss (percent usual body weight [PUBW], ≤95%) compared with 84 without weight loss (PUBW, >95%; 31.4 ± 1.5 versus 30.5 ± 2.1 kcal/kg/d, respectively). Symptoms identified by multivariate analysis as occurring significantly more frequently in populations with weight loss included abdominal fullness (P < 0.001), taste change (P < 0.002), vomiting (P < 0.005), and mouth dryness (P < 0.02). There was no difference in frequency of symptoms between patients with or without prior chemotherapy. These results indicate that gastrointestinal/oral symptoms potentially influencing weight loss are prevalent early in the course of cancer patients with unresectable disease, regardless of current nutritional status, caloric intake, or prior therapy experience.

Dietary Intake and Counseling, Weight Maintenance, and the Course of HIV Infection

OBJECTIVE To define relationships among dietary intake and counseling, weight maintenance, and the clinical course of patients infected with the human immunodeficiency virus (HIV). DESIGN A prospective cohort study in an HIV clinic in a county hospital. SUBJECTS HIV-infected patients (68 with and 40 without acquired immunodeficiency syndrome [AIDS]) who had a good performance status and no chronic diarrhea were assessed at entry to the study and after 6 months. The following assessments were made: energy and nutrient intake based on 7-day food records, anthropometric measurements, immunologic function as lymphocyte T-cell subpopulations (ratio of CD4 to CD8), and serum cholesterol level. Patients were monitored to determine clinical outcome. INTERVENTION All patients received standardized dietary counseling designed to address identified intake deficiencies and maintain body weight. MAIN OUTCOME MEASURES Changes in energy and nutrient intake, body weight, and clinical outcome (ie, time to AIDS-defining illness and overall survival time). STATISTICAL ANALYSES PERFORMED Group differences (HIV group vs AIDS group) were sought using chi 2 analyses and Students t test. A multivariate regression model was used to determined the best predictors of clinical outcome. RESULTS At baseline, total energy intake (based on 30 kcal/kg usual body weight) was adequate in both HIV and AIDS patients (101 +/- 4% and 103 +/- 5% [mean +/- standard deviation] of need, respectively). Despite dietary counseling and continued maintenance of energy intake, body weight, serum cholesterol level, and CD4 level progressively decreased. Consequently, saturated fat intake was found to be inversely related (P < .01) to serum cholesterol level. Clinical outcome (after 3.5 years) was associated with baseline ratio of CD4 to CD8 (P < .001), weight (P < .01), and serum cholesterol level (P < .001). Multivariate analysis related ratio of CD4 to CD8 (P < .001) and weight maintenance (P < .001) to favorable outcome in the final model. APPLICATIONS Weight loss in patients with HIV infection is independently prognostic of clinical outcome, and development of hypocholesterolemia is not favorable for clinical outcome. Because weight loss progresses despite conventional dietary counseling to identify energy need, interventions earlier in the disease course should be considered along with increased target levels for energy intake.

Recent implications of weight loss inlung cancer management

Successful lung cancer management has been hindered by the limited efficacy of dietary and pharmacologic interventions to prevent or reverse cancer-associated weight loss. The addition of total parenteral nutrition to chemotherapy in early trials was associated with survival detriment. Dietary counseling and enteral supplement use are common strategies that, when evaluated in randomized trials, do not improve anthropometrics or clinical outcome in lung cancer. Pharmacologic agents including corticosteroids, cyproheptadine, growth hormone, hydrazine sulfate, dronabinol, and pentoxyphylline also have failed to improve even anthropometric parameters in this condition. Megestrol acetate use is associated with appetite stimulation and non-fluid weight gain but, when evaluated in small cell lung cancer patients receiving defined chemotherapy, failed to improve global quality of life, and survival and was associated with toxicity. New strategies for nutrition-based interventions in lung cancer cachexia must consider their potential influence on tumor growth as well as on nutritional status. Recent lung cancer prognostic analyses have identified gender differences in outcome and weight loss that suggest potential targets for combined hormonal and nutrition interventions. Emerging information regarding the influence of specific fatty acids on tumor growth and cachexia development have identified additional approaches for future evaluation.

THE SCOPE OF NUTRITION INTERVENTION TRIALS WITH CANCER-RELATED ENDPOINTS

The National Cancer Institute currently is supporting three full‐scale dietary modification trials with cancer‐related endpoints. These studies are the dietary component of the Womens Health Initiative, designed to determine whether a low‐fat diet will reduce the incidence of breast and colorectal cancer and/or coronary heart disease; the Womens Intervention Nutrition Study, designed to test whether a dietary fat reduction program will decrease breast cancer recurrence and increase patient survival; and the Polyp Prevention Trial, designed to determine whether a low‐fat, high‐fiber diet will reduce the recurrence of adenomatous polyps. Design issues associated with these full‐scale dietary modification outcome trials have been addressed successfully in a series of feasibility studies. The ability to achieve a sustained reduction of 50% in dietary fat intake with maintenance of nutritional adequacy has been demonstrated in randomized trials of postmenopausal populations with resected breast cancer and in populations at increased risk for breast cancer. In these studies comparing dietary fat reduction programs with control lifestyles, a series of associated biologic changes, consistent with the self‐reported dietary alterations, have been observed. These changes include body weight reduction, serum and/or plasma estradiol concentration reduction, fasting plasma cholesterol concentration reduction, and alteration in free fatty acid levels. Such results provide a substantial basis for reliably estimating the level of adherence that can be anticipated in trials of dietary change, a prerequisite for appropriate calculation of the sample size needed for multicenter, full‐scale outcome studies. As a result, the efficacy of a series of dietary alterations (including fat reduction, fiber addition, and/or increased fruit and vegetable intake) on cancer‐related endpoints with potential major public health significance (breast cancer recurrence, breast cancer development, and colonic polyp recurrence) now are being addressed definitively in prospective clinical trials.

Altered metabolism and mortality in patients with colon cancer receiving chemotherapy

To identify the metabolic effects of 5-fluorouracil and hydrazine sulfate therapy, 22 patients with colon cancer were admitted prospectively to a Clinical Research Center for serial measurement of counter-regulatory hormones, fasting hepatic glucose production (HGP), intravenous glucose tolerance test, plasma leucine appearance (LA) and leucine oxidation. Combined therapy was associated with a significant reduction in fasting glucose level (98 ± 2 mg/dL to 94 ± 2, P < 0.025) without a significant fall in fasting HGP (2.09 ± 0.11 mg/kg/min versus 2.03 ± 0.13; P > 0.05). The decreased fasting glucose value was associated with a mild but not statistically improved glucose disposal rate in response to the intravenous glucose tolerance test (1.34 ± 0.07 %/min vs 1.47 ± 0.11, P = 0.15). Plasma leucine appearance was significantly reduced after 2 months of therapy (63.3 ± 3.0 μmol/kg/hr vs 57.1 ± 3.9 μmol/kg/hr; P < 0.025), but leucine oxidation (11.5 ± 1.1 μmol/kg/hr vs 11.2 ± 1.1 μmol/kg/hr) was not altered. Despite the fact that plasma triiodothyronine concentrations significantly increased with therapy, it was not associated with plasma LA. Half of the patients with cancer died 14 ± 4 months after the study, and the other half were alive 58 ± 2 months later. Survival time can be estimated with 59% accuracy using plasma LA, HGP, carcino-embryonic antigen, and insulin concentration. Multiple regression analysis identified that plasma LA was related directly to length of survival time, and baseline HGP, carcino-embryonic antigen, and insulin concentration were related inversely to length of survival. Unlike an elevated HGP seen in cancer cachexia, based on the association of a higher plasma LA and longer survival rate, an elevation in plasma LA may not be an unfavorable response to cancer. Further research is required to validate the predictability of baseline metabolic markers with survival rate in the cancer population.

Diet composition and lipoprotein lipase ( EC 3.1.1.34) activity in human obesity

1. Adipose tissue lipoprotein lipase (EC 3.1.1.34; AT-LPL), a rate-limiting enzyme in triglyceride storage in adipose tissue, is hormonally regulated and may be important in the maintenance of obesity. 2. In twelve obese women, AT-LPL activity was measured before weight loss, during weight loss and after 1 and 2 weeks of weight maintenance on either a high-carbohydrate or a high-protein diet. 3. When related to tissue weight, AT-LPL activity during the 2 weeks of weight maintenance was higher than the initial AT-LPL activity; there was no difference when activity was expressed per cell. 4. Changes in AT-LPL activity were not affected by diet composition. AT-LPL activity correlated with insulin levels and a change in insulin sensitivity of AT-LPL was observed after weight loss.