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R T Chlebowski

Publications and source records attributed to R T Chlebowski.

At least 37 records · Page 2Linked to original sources
PubMed1993

Adherence to a dietary fat intake reduction program in postmenopausal women receiving therapy for early breast cancer. The Women's Intervention Nutrition Study.

PURPOSE: To evaluate the feasibility of integrating a program based on dietary fat intake reduction into adjuvant treatment strategies for postmenopausal women receiving therapy for early breast cancer. PATIENTS AND METHODS: Two hundred ninety postmenopausal women with localized (stage I to IIIa) breast cancer receiving conventional systemic therapy provided informed consent and were randomized in a multicenter trial to either a dietary intervention group receiving a program of individualized instruction for reducing total fat intake or a dietary control group with minimal dietary counseling. RESULTS: Significantly reduced (P < .001) fat intake (in terms of percent calories derived from fat) was observed in the intervention group versus the control group at 3 months (20.3% +/- 2.4% v 31.5% +/- 2.6%, mean +/- SD, respectively) and maintained throughout 24 months of observation. The 50% reduction in daily fat-gram intake (from 66 +/- 23 to 33 +/- 14 g, P < .001) seen at 6 months was associated with reduced saturated fat, monounsaturated fat, polyunsaturated fat, and linoleic acid (P < .001). Significantly lower body weight was also seen in intervention compared with control patients at all observation periods, resulting in a 3.3-kg weight difference 18 months after randomization (P < .001). CONCLUSION: Substantial and sustained dietary fat reduction with associated weight change can be achieved at relatively low cost within the context of conventional multimodality clinical management of postmenopausal women with localized breast cancer. This result supports the feasibility of conducting a full-scale evaluation of the influence of dietary fat intake reduction on the clinical outcome of breast cancer patients.

Aged↗
PubMed1992

Effects of tamoxifen adjuvant therapy and a low-fat diet on serum binding proteins and estradiol bioavailability in postmenopausal breast cancer patients.

Serum was collected at intervals from postmenopausal breast cancer patients to determine the effects of tamoxifen adjuvant therapy and a low-fat dietary intervention, alone and in combination, on sex hormone-binding globulin (SHBG) concentrations and circulating estradiol bioavailability. Serum corticosteroid-binding globulin and follicle-stimulating hormone were also assayed as indicators of patient compliance to tamoxifen therapy. The immunoreactive SHBG concentration was higher (P less than 0.001) in 22 patients who had been treated with tamoxifen for 6-36 weeks when first sampled, compared with 27 who were not receiving tamoxifen therapy. Tamoxifen also produced a reduction in the percentage non-protein-bound estradiol (P less than 0.001) and percentage albumin-bound estradiol (P less than 0.01), the two biologically available fractions, and a corresponding increase in the percentage SHBG-bound estradiol (P less than 0.01). A longitudinal study of 7 patients showed significant reductions in the percentage of albumin-bound estradiol and an increased percentage of SHBG-bound estradiol, after 3-6 months of tamoxifen; after 12-18 months there was also a significant decrease in the non-protein-bound estradiol fraction. We conclude that in postmenopausal breast cancer patients the redistribution of circulating estradiol, with reduced bioavailability, provides an additional mechanism to those demonstrated previously for the therapeutic activity of tamoxifen. Another 12 patients receiving tamoxifen and 8 who were not were followed for 6-12 months on a low-fat diet (fat comprised 20% of the total calories). The dietary intervention had no effect on the serum SHBG concentration or the estradiol distribution. Although tamoxifen increased the serum corticosteroid-binding globulin and partially suppressed the follicle-stimulating hormone concentrations, the responses obtained were less consistent compared with those of the SHBG levels.

Biological Availability↗
PubMed1992

Adjuvant dietary fat intake reduction in postmenopausal breast cancer patient management. The Women's Intervention Nutrition Study (WINS).

Management of localized breast cancer now commonly involves a breast-sparing approach combined with systemic adjuvant therapy resulting in improved cosmetic results and patient survival. Reducing dietary fat intake represents a conceptually new approach to further improve outcome of patients with resected breast cancer. The rationale supporting evaluation of dietary fat reduction in the management of patients with localized breast cancer is based on: (1) epidemiologic observations (along with biochemical and hormonal correlates) of major differences in stage-by-stage survival of patients with localized breast cancer comparing outcome in countries with low fat (Japan) versus high fat (U.S.A.) dietary intakes; (2) relationships between dietary fat intake and factors prognostic of clinical outcome in patients with established breast cancer; (3) effects of weight gain (especially that associated with adjuvant chemotherapy) on breast cancer clinical outcome; (4) in vivo animal studies demonstrating adverse influence of increased dietary fat intake (especially linoleic acid) on growth and metastatic spread of mammary cancer; (5) direct adverse effects of increased linoleic acid on human breast cancer growth in vitro; (6) plausible mechanisms which could mediate the effects of dietary fat intake reduction on breast cancer growth and metastatic spread; (7) demonstration of adherence to dietary fat reduction regimens in ongoing clinical feasibility studies including those involving postmenopausal patients with resected breast cancer; and (8) favorable sample size requirements for definitive assessment of dietary fat intake reduction influence on breast cancer growth and metastases (using as endpoints relapse-free survival and overall survival) in postmenopausal breast cancer patients with localized disease.

Animals↗
PubMed1992

Current attitudes and practice of American Society of Clinical Oncology-member clinical oncologists regarding cancer prevention and control.

PURPOSE AND METHODS: A nationwide needs assessment survey including a validated Cancer Prevention and Early Detection Attitude Inventory of 1,500 randomly selected American Society of Clinical Oncology (ASCO)-member clinical oncologists was conducted via a 67-item, mailed questionnaire to assess practice and attitudes regarding cancer prevention and control. RESULTS: Responses of 729 physicians from 48 states representing medical (57%), radiation (17%), surgical (16%), and pediatric oncology (6%), and hematology/other (4%) fields were obtained. Except for ambivalence regarding an important role for diet in cancer causation, cancer prevention and control recommendations were widely endorsed despite skepticism about their impact on reducing deaths from cancer. Surprisingly, a significantly (P less than .001) more favorable attitude for cancer prevention and control issues was found in physicians with greater than 20 years practice compared with younger oncology colleagues, as measured by a 22-item Cancer Prevention and Early Detection Attitude Inventory. Among all physicians, participation in cancer therapy trials exceeded that in cancer prevention and control trials (91% v 27%, P less than .01). Formal instruction during postgraduate training in cancer screening (34%) or prevention (23%) was received by few oncologists; nonetheless, 69% considered themselves a resource for cancer prevention and control issues in their practice communities. Of potential barriers to cancer prevention and control activity, only lack of patients without cancer (53%) and difficulty in including such activity economically into clinical practice (65%) were majority selections. Importantly, 64% agreed they could "motivate their patients to change lifestyle to reduce cancer risk." CONCLUSION: Clinical oncologists may represent a potential resource for implementation of cancer prevention and control objectives if economically feasible models for their use in practice settings can be identified.

Adult↗
PubMed1991

Nutritional support of the medical oncology patient.

Our current ability to favorably influence the adverse consequences of malnutrition in adult patients with established cancer is quite limited. Nutrient provision alone has not been successful in this regard. In fact, the approach of managing cancer patients with weight loss by solely providing calories is almost entirely extrapolated from clinical situations in which the presence of cancer is not a confounding problem and, therefore, may well be seriously flawed. These conclusions may not apply to situations in which special considerations hold, such as childhood malignancies and bone marrow transplantation. Current clinical management strategies for the cancer patient with weight loss require appropriate attention to the potential influence of the selected intervention on more than one parameter. As illustrated in Figure 1, nutritional support, whether by nutrient provision, pharmacologic administration, or a combination approach, differentially influences several parameters including nutritional status, abnormal host metabolism, gastrointestinal symptoms, and/or tumor growth. Changes in these parameters will influence the true end points with clinical relevance, which are patient survival and quality of life. Increased survival of patients with metastatic cancer has been difficult to achieve, even using chemotherapeutic regimens targeted directly at cancer growth. Similarly, nutritional support for patients with advanced cancer has not demonstrated improvement in this refractory parameter. Therefore, at the present time, clinicians must judge whether a nutritional support modality will favorably or unfavorably influence patient quality of life. This end point is of emerging importance in studies of nutritional support in cancer populations. Potential interrelationships among parameters influenced by nutritional support and their effect on clinically relevant end points are conceptually outlined in Figure 1. It is likely that concurrent attention to both optimal provision of nutrients and reversal of abnormal metabolism will be required if successful nutritional support approaches are to be described. Currently emerging clinical results provide some optimism for the future, but they do not unequivocally support the present routine application of any one particular nutrition support strategy for the medical patient with cancer.

Cachexia↗
PubMed1990

Relationship of hepatic glucose production to growth hormone and severity of malnutrition in a population with colorectal carcinoma.

To define the influence of weight loss on the severity of metabolic abnormalities in patients with the same stage and primary site of cancer, hepatic glucose production (HGP) and nutritional status were determined in 44 patients with advanced, Stage D colorectal carcinoma and compared to values in seven cancer-free controls. The colorectal cancer patients were divided into three groups based upon percentage of ideal body weight. HGP was determined in all participants after an overnight fast by using a 3- or 4-h primed, continuous infusion of [6-3H]glucose. Fasting glucose, insulin, cortisol, thyroxine, triiodothyronine, and growth hormone values were also determined. Mean HGP was significantly elevated in colorectal carcinoma patients versus normal subjects (2.35 +/- 0.89 (SD) mg/kg/min versus 1.75 +/- 0.16; P less than 0.01). The most severely malnourished group (ideal body weight less than 90%) demonstrated the greatest increase in HGP (2.98 +/- 0.73 mg/kg/min). Growth hormone mean fasting levels were significantly elevated in the colorectal carcinoma population compared to the normal subjects (2.9 +/- 3.1 ng/ml versus 0.5 +/- 0.2; P less than 0.001). The most severely malnourished group also demonstrated the highest growth hormone levels. The rate of HGP was significantly correlated with fasting growth hormone levels (r = 0.71; P less than 0.001) and not significantly correlated to cortisol, insulin, thyroxine, triiodothyronine, or glucose levels in carcinoma patients. Thus, the elevation in HGP seen in patients with colorectal carcinoma is related to the severity of weight loss and is associated with elevations in fasting growth hormone.

Carcinoma↗
PubMed1990

Hydrazine sulfate influence on nutritional status and survival in non-small-cell lung cancer.

This randomized, prospective, placebo-controlled clinical trial compares the influence on nutritional status and survival of hydrazine sulfate with placebo addition to cisplatin-containing combination chemotherapy in patients with unresectable non-small-cell lung cancer (NSCLC). The trial consisted of 65 patients with advanced, unresectable NSCLC who had had no prior chemotherapy, were at least partially ambulatory (Eastern Cooperative Oncology Group [ECOG] performance status [PS] level 0-2), and who had adequate hematologic, renal, and hepatic function. All patients received the same defined combination chemotherapy (cisplatin, vinblastine, and bleomycin) and the same defined dietary counseling with the addition of either three times daily oral hydrazine sulfate (60 mg) or placebo capsules. Hydrazine sulfate compared with placebo addition to chemotherapy resulted in significantly greater caloric intake and albumin maintenance (P less than .05). Considering all patients, survival was greater for the hydrazine sulfate compared with placebo group (median survival, 292 v 187 days), but the difference did not achieve statistical significance. In favorable PS patients (PS 0-1), survival was significantly prolonged (median survival, 328 days v 209 days; P less than .05) for hydrazine sulfate compared with placebo addition. In a multifactor analysis, PS, weight loss, and liver involvement were the final variables. Objective response frequency and toxicity were comparable on both arms. Hydrazine sulfate may favorably influence nutritional status and clinical outcome of patients with NSCLC. Further definitive studies of hydrazine sulfate addition to therapeutic regimens in NSCLC are warranted.

Antineoplastic Agents↗
PubMed1990

Diet intervention methods to reduce fat intake: nutrient and food group composition of self-selected low-fat diets.

A multicentered pilot study was conducted to test an intervention protocol designed to reduce fat intake to 15% of energy intake. Eligible subjects were postmenopausal women with stage II breast cancer whose baseline fat intake was more than 30% of energy intake. The low-fat diet intervention protocol consisted of bi-weekly individual counseling sessions with emphasis on substitution of lower-fat foods for high-fat foods and maintenance of nutritional adequacy. Nutrient intakes were calculated from 4-day food records collected at baseline and after 3 months of diet intervention. Mean daily fat intake for the 17 patients on the low-fat diet dropped significantly from 38.4 +/- 4.3% of energy intake at baseline to 22.8 +/- 7.8% at 3 months (p less than .001). A 25% reduction in mean energy intake, from 1,840 +/- 419 kcal at baseline to 1,365 +/- 291 kcal at 3 months, was accompanied by significant increases in protein and carbohydrate as percent of energy intake. A mean weight loss of 2.8 kg and a 7.7% reduction in serum cholesterol were observed; both changes were significant at the p less than .01 level. Absolute intakes of zinc and magnesium were significantly reduced. However, mean intake on the low-fat diet for 14 vitamins and minerals, including zinc and magnesium, exceeded two-thirds of the 1989 Recommended Dietary Allowances (RDAs). When expressed as nutrient density (i.e., amount of nutrient per 1,000 kcal), increases were observed for all micronutrients. These results support the hypothesis that a nutritionally adequate low-fat diet can be successfully implemented in a highly motivated, free-living population.

Aged↗
PubMed1989

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], less than or equal to 95%) compared with 84 without weight loss (PUBW, greater than 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 less than 0.001), taste change (P less than 0.002), vomiting (P less than 0.005), and mouth dryness (P less than 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.

Adult↗
PubMed1989

Mitoxantrone use in breast cancer patients with elevated bilirubin.

To determine the safety and efficacy of mitoxantrone use in hyperbilirubinemic breast cancer patients, a prospectively determined dosage schedule was evaluated in a multi-center trial. Pretreatment bilirubin prospectively defined three groups: Controls (with normal bilirubin) and two Study groups (with either moderate or severe bilirubin increase). Bilirubin determined initial mitoxantrone dose as well: bilirubin less than 3.5 mg/dl, 14 mg/m2; and bilirubin greater than or equal to 3.5 mg/dl, 8 mg/m2. Mitoxantrone at 14 mg/m2 was well tolerated in patients with moderate hepatic dysfunction. Patients with severe hepatic dysfunction demonstrated a mixed toxicity picture, with performance status (ECOG level 3) defining a population with limiting myelosuppression and/or early death. The survival of Study patients with severe hepatic dysfunction (median 17 days) was significantly worse than both Control (p less than 0.01) and Study (p less than 0.05) patients with lower bilirubin. Entry performance status (ECOG level 0-2 versus level 3) profoundly influenced survival (median survival 222 days versus 25 days, respectively, p less than 0.0001). Objective responses were seen in patients with both normal and elevated bilirubin. Bilirubin reduction following mitoxantrone commonly occurred, representing at least an indicator of favorable prognosis. Recommendations for mitoxantrone use include: 1. Patients with moderate bilirubinemia tolerate 14 mg/m2 mitoxantrone with reasonable chance for benefit. 2. Patients with severe hepatic dysfunction and poor performance status should not be given mitoxantrone. A definitive recommendation regarding use of reduced 8 mg/m2 mitoxantrone in patients with severe hyperbilirubinemia and favorable performance status requires further study.

Adenocarcinoma↗
PubMed1989

Unpublished Data Summaries and the design and conduct of clinical trials. The Nutrition Adjuvant Study experience and commentary.

A trend in cancer clinical investigation has been the application of new analytic techniques and reporting forums to summarize developing trial results. Examples include: Consensus Conferences, Meta-Analyses, and most recently (in the breast cancer area), the "Clinical Alert." These Unpublished Data Summaries have been widely disseminated in lay and scientific communities and have frequently engendered debate conducted in the absence of primary information. We now report the impact of this process on a national, cooperative group effort (the Nutrition Adjuvant Study [NAS] ) designed to test a novel hypothesis involving dietary fat reduction as potential adjuvant breast cancer treatment. It is clear that these Unpublished Data Summaries in the breast cancer area directly resulted in changes in the NAS protocol design and may have influenced patient accrual. The challenge for clinical investigators and governmental agencies is to integrate the positive aspects of the new information forums with those of traditional "peer-review" publication into a system where the conduct of clinical investigation in a timely manner can be facilitated.

Breast Neoplasms↗
PubMed1989

Combination versus sequential single agent chemotherapy in advanced breast cancer: associations with metastatic sites and long-term survival. The Western Cancer Study Group and The Southeastern Cancer Study Group.

Two hundred and twenty-two patients with advanced breast cancer were randomised in two separate trials of similar design to either concomitant combination treatment or sequential use of the same drugs given as single agents changed only at disease progression. Both trials used cyclophosphamide, methotrexate, 5-fluorouracil and prednisone; the WCSG using triiodothyronine and the SECSG using vincristine as the remaining agent. A common data base was generated for these trials and combined for analysis. Considering all patients, combination treatment was associated with a significantly increased response (46 versus 25%, P less than 0.05) but not survival improvement. For the 141 patients without liver involvement, survival was closely comparable in both treatment arms. Combination therapy did result in significant survival benefit for patients with liver involvement (P less than 0.05). These studies demonstrate: (1) in the majority of breast cancer patients, sequential single agent therapy can result in survival comparable to combination treatment; and (2) sole consideration of response frequency does not represent the optimal criterion to compare therapeutic approaches in advanced breast cancer.

Adenocarcinoma↗
PubMed1989

Nutritional status, gastrointestinal dysfunction, and survival in patients with AIDS.

The clinical course of 71 patients with acquired immune deficiency syndrome (AIDS) was evaluated to determine relationships among nutritional status, gastrointestinal symptoms and survival. At baseline, weight loss was present in 98%, hypoalbuminemia (less than 3.5 g/dl) was present in 83%, and gastrointestinal symptoms included pharyngitis (54%), diarrhea (42%), nausea (23%), dysphagia (21%), and anorexia (18%). Both the magnitude of body weight loss and the serum albumin level were strongly associated with life-table analysis of survival. For weight loss, median survival of 520 vs. 48 days occurred in patients with less than 10% versus greater than 20% baseline weight loss, respectively (p less than 0.01). The substantial influence of serum albumin on survival is outlined below. (table; see text) In almost all cases, serial evaluation demonstrated progressive linear decrease in body weight and albumin. In patients with normal baseline albumin, the rate of 0.7 mg/dl albumin decrease per day was less than half that in patients with baseline hypoalbuminemia. A projected "time to develop an albumin level less than 2.5 g/dl" was calculated for patient groups based on initial albumin level and the rate of albumin decrease. The calculated interval was similar to the actual median survival time observed in these groups. We conclude that 1) nutritional status may represent a major determinant of survival in AIDS and 2) the rate of albumin decrease may define a function limiting survival of individual patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Long-term survival following levamisole or placebo adjuvant treatment of colorectal cancer: a Western Cancer Study Group Trial.

In 1976, the Western Cancer Study Group initiated a prospectively randomized, double-blind trial of an 18-month adjuvant program comparing levamisole with placebo treatment following surgical resection in patients with colorectal adenocarcinoma. After stratification for site of disease (colon vs. rectum) and stage (B vs. C), 78 patients were entered. The levamisole schedule was 2.5 mg/kg/day given on days 1 and 2 of each week. The median follow-up of entered patients is now 7.5 years. Toxic effects of treatment were minimal. However, no long-term survival advantage was associated with levamisole compared to placebo administration in this population with resected large-bowel adenocarcinoma.

Adenocarcinoma↗