PubMed Health⌕ Search

Biomedical subjects

R T Chlebowski

Publications and source records attributed to R T Chlebowski.

At least 55 records · Page 3Linked to original sources
PubMed1987

Effect of hydrazine sulphate on whole-body protein breakdown measured by 14C-lysine metabolism in lung cancer patients.

In a prospective double-blind trial twelve malnourished patients with lung cancer were randomised to receive either placebo or hydrazine sulphate (60 mg three times daily) for 30 days. Fasting lysine flux was determined by a primed 4-hour continuous infusion of 14C-lysine before and after one month of hydrazine treatment. Baseline plasma lysine flux was 2580 (SD 580) mumol/h for the placebo group and 2510 (440) mumol/h for the hydrazine group. After one month the placebo group showed a slight rise to 2920 (450) mumol/h (p = 0.08) and the hydrazine group showed a significant fall to 1840 (750) mumol/h (p less than 0.05); serum albumin fell in the placebo group and was unchanged in the hydrazine group. Administration of hydrazine sulphate to reduce aminoacid flux may favourably influence the metabolic abnormalities in cancer cachexia.

Adult↗
PubMed1987

Hydrazine sulfate in cancer patients with weight loss. A placebo-controlled clinical experience.

Hydrazine sulfate was evaluated using 24-hour dietary recalls and body weight determinations before and after 30 days of either placebo or hydrazine (60 mg, 3 times/d) oral administration in 101 heavily pretreated cancer patients with weight loss. After 1 month, 83% of hydrazine and only 53% of placebo patients completing repeat evaluation maintained or increased their weight (P less than 0.05). In addition, appetite improvement was more frequent in the hydrazine group (63% versus 25%, P less than 0.05). Although caloric intake was only slightly greater in hydrazine-treated patients, an increased caloric intake was more commonly associated with weight gain in patients receiving hydrazine compared with those receiving placebo (81% versus 53%, respectively). Hydrazine toxicity was mild, with 71% of patients reporting no toxic effects. Hydrazine sulfate circulatory levels were obtained from a subset of 14 patients who completed 30 days of treatment, with a single sample obtained in the morning at least 9 hours after the last dose. Mean maintenance hydrazine sulfate levels, determined using a spectrofluorometric assay, ranged from 0 to 89 ng/ml (mean 45 +/- 16 ng/ml). These data, which demonstrate an association between 1 month of hydrazine sulfate administration and body weight maintenance in patients with cancer, suggest future clinical trials of hydrazine sulfate are indicated to definitively assess its long-term impact on important clinical outcome parameters in defined cancer populations.

Appetite↗
PubMed1987

A breast cancer Nutrition Adjuvant Study (NAS): protocol design and initial patient adherence.

To evaluate the feasibility of using a reduction in dietary fat intake as a component of treatment regimens for patients with resected breast cancer, a multi-disciplinary cooperative group protocol was developed. Females 50 to 75 years of age with stage II breast cancer who completed primary local therapy were eligible for randomization to a Control Dietary Group in which dietary fat intake was to remain unchanged from baseline level (at approximately 38% of calories derived from fat) and an Intensive Intervention Dietary Group designed to reduce dietary fat intake. Both Dietary Groups were given tamoxifen 20 mg/day. To facilitate early experience with dietary regimen delivery, patients entered during an initial pilot phase could receive any chemotherapy and/or hormonal treatment. A prerandomization nutrition 'run-in' of clinically eligible patients assessed adherence to nutrition data collection procedures and screened patients for nutrition eligibility criteria. Of 59 patients beginning 'run-in', 49 were randomized and, at present, 32 have completed at least three months follow-up. The change in dietary fat intake (as assessed by Four Day Food Records) seen in both arms is outlined below. Formula see table. The 56% reduction in total daily fat gram intake achieved in the Intensive Intervention Dietary Group suggests that protocols designed to reduce dietary fat intake in an adjuvant treatment setting can be developed and implemented using a multi-institutional, cooperative group approach.

Adult↗
PubMed1987

Doxorubicin and methotrexate on a weekly schedule in patients with sarcomas.

Fifty-five sarcoma patients with advanced measurable disease were treated with a doxorubicin and methotrexate combination in which both drugs were given on a weekly schedule. Patients received doxorubicin and methotrexate at three prospectively evaluated treatment levels with doxorubicin dosage ranging from 0.5 to 0.725 mg/kg/week and methotrexate dosage ranging from 0.25 to 0.375 mg/kg/week. Objective responses were seen in 11 of 39 (28%) patients receiving the two higher doxorubicin-methotrexate treatment levels where doxorubicin dose was greater than 0.5 mg/kg/week compared to only 2 of 16 (12%) patients receiving lower doxorubicin levels (p less than 0.05), suggestive of a dose-response relationship. Toxicity of this regimen was manageable but stomatitis was appreciable, seen in 30% of patients. These results support the activity of weekly doxorubicin in sarcoma therapy. However, no apparent improvement was associated with addition of conventional dose methotrexate to weekly doxorubicin treatment.

Adolescent↗
PubMed1987

Synergistic cytotoxicity between menadione and dicumarol vs. murine leukemia L1210.

The water-soluble derivative of vitamin K, menadiol sodium bisulfite (K3), and the related anticoagulant dicumarol, inhibited growth of murine leukemia L1210 in liquid suspension culture. K3, but not dicumarol, cytotoxicity was abrogated by 1 mM cysteine. Isobolographic analysis of the effect of K3-dicumarol combinations, in the concentration ranges between 5 and 75 microM, on L1210 growth, indicated synergy between the two drugs. K3 (10 microM) caused a 3-fold stimulation of KCN-resistant O2 consumption by L1210 cells; addition of 50 microM dicumarol did not enhance KCN-resistant O2 consumption further, suggesting that K3-dicumarol synergy in L1210 was not due to dicumarol-mediated augmentation of K3-semiquinone-free radical formation. We examined the effect of dicumarol addition on L1210 cellular metabolites known to be affected by K3, i.e., glutathione, NADPH and ATP. Dicumarol prevented the elevation of the glutathione pool caused by less than or equal to 18 microM K3. K3-dicumarol combinations depleted the NADPH pool significantly, at concentrations of each which did not affect the NADPH pool. No synergistic effect on the ATP pool was observed. Thus, although the mechanism of K3-dicumarol synergy vs. leukemia remained unclear, it was possible that effects on the glutathione and/or NADPH pools contributed. We also investigated the effect of K3 and dicumarol on 45Ca++ transport by L1210 cells because of their effects on glutathione. Neither drug affected 45Ca++ influx or efflux rate constants. However, equilibrium 45Ca++ uptake was suppressed by K3 at concentrations lower than those which depleted glutathione.

Adenosine Triphosphate↗
PubMed1986

Pathophysiology of malnutrition in the adult cancer patient.

A number of common metastatic cancers are associated with marked weight loss at the time of diagnosis. Cancer patients with weight loss at the time of diagnosis have decreased mean survival compared to similar cancer patients without weight loss. Provision of excess calories alone does not appear to change median survival in patients with advanced cancer and many patients either maintain body weight or lose weight while receiving calories which would be predicted to result in weight gain. The authors recently have extended their studies to head and neck cancer patients without detectable metastatic disease in order to detect systemic metabolic effects of a localized tumor. These patients failed to gain weight despite the administration of apparently adequate calories by continuous enteral alimentation. Abnormalities of carbohydrate metabolism with secondary effects on fat and protein metabolism have been identified in several populations of patients with common cancers. These abnormalities offer potential points of intervention which may enhance nutritional therapy as rehabilitation and as a potential biological modifier of the response of specific cancers to chemotherapy, radiation therapy, or surgery.

Adult↗
PubMed1986

Influence of nandrolone decanoate on weight loss in advanced non-small cell lung cancer.

The short term addition of nandrolone decanoate to combination chemotherapy given to patients with unresectable non-small cell lung cancer was evaluated in a randomized, prospective trial. Patients were treated with doxorubicin 50 mg/M2 intravenously, cyclophosphamide 300 mg/M2 intravenously, CCNU 50 mg/M2 orally, vincristine 1.4 mg/M2 intravenously, with and without cisplatin 50 mg/M2 intravenously, all given every 28 days. In addition, patients were randomized to receive either nandrolone decanoate 200 mg intramuscularly weekly for 4 weeks or no additional therapy. Patient age, disease extent, performance score, and pretreatment weight loss were similar in the two treatment arms. Objective antitumor response frequency was comparable on both treatment arms with median survival somewhat longer for patients receiving the androgen (median survival 5.5 months without and 8.2 months with nandrolone decanoate). There was a trend for less severe weight loss on the nandrolone decanoate arm (average weight loss 0.8 +/- 0.15 kg versus 0.21 +/- 0.18 kg, respectively), with half as many patients experiencing weight loss on nandrolone decanoate (25% versus 12%). A separate concurrent study has demonstrated decreased free testosterone levels in 66% of patients with advanced cancer studied prior to chemotherapy treatment, therefore, further prospective studies in which pretreatment testosterone levels are used to guide androgen administration are needed to define more precisely a role for androgen replacement therapy in non-small cell lung cancer.

Anabolic Agents↗
PubMed1986

Long-term survival following relapse after 5-FU but not CMF adjuvant breast cancer therapy.

Beginning in 1974, patients with greater than or equal to 4 nodes positive following mastectomy were randomized to receive either 5-FU i.v. weekly or CMF i.v. every 2 weeks, both given for 12 months. Median follow-up now exceeds 112 months with nine year results below: (table; see text) Early results based on relapse-free survival favored CMF, but more patients currently are alive on the 5-FU arm. As the survival curves cross at 40 months, the 20% survival advantage for 5-FU did not achieve statistical significance. For 34% of patients failing adjuvant 5-FU, use of combination chemotherapy after relapse (commonly with CMFVP or CMF) resulted in long term survival. In contrast, long-term survival for patients failing adjuvant CMF was unusual. Relapse was detected while under weekly observation in a greater proportion of patients on 5-FU (36%) compared to CMF (6%) adjuvant treatment (p less than 0.05), potentially influencing tumor burden at recurrence. Hormonal therapy or radiation therapy as initial therapy after relapse was ineffective, with no long term survivors resulting on either arm. Weight increase on adjuvant chemotherapy was commonly seen, with weight increase greater than 10 kg associated with a poor prognosis. We conclude that initial improvement in relapse-free survival may not predict long term survival in adjuvant breast cancer trials since both the specific adjuvant therapy given pre-relapse as well as the type of salvage therapy given post-relapse may influence ultimate patient outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Metabolic abnormalities in cancer patients: carbohydrate metabolism.

Weight loss in patients with a variety of cancers is associated with a poor prognosis. Consistent abnormalities of carbohydrate metabolism are seen in cancer patients with weight loss and appear to represent derangements in host metabolism that are induced by the presence of cancer. To define therapeutic strategies to improve the poor clinical outcome for patients with cancer cachexia, investigations are under way to define the relationships among glucose metabolism, altered energy expenditure, caloric intake, weight loss, and clinical outcome.

Animals↗
PubMed1985

Influence of nutritional status on circulatory ribonuclease C levels in patients with cancer.

The influence of a variety of clinical and biochemical parameters on the activities in serum of ribonuclease (RNAse) selective for polycytidylic acid (RNAse C) were examined in 90 adult patients with cancer. The clinical data base determined on each patient included: RNAse C level, carcinoembryonic antigen (CEA) level, age, sex, race, presence (or absence of metastases, type of cancer, site of metastasis, renal function blood urea nitrogen [BUN], creatinine), hepatic function (bilirubin, alkaline phosphatase), and nutritional status (percent ideal body weight, percent weight loss, and albumin). Common tumor types studied included: colon (21), lung (18), breast (15), and hepatocellular carcinoma (10). For comparison, 175 nonmalignant control patients were studied to establish the normal range for RNAse. In patients with cancer, RNAse levels were increased in 57% and CEA levels were above 10 ng/dl in 36%. Although patients with BUN greater than 25 mg/dl or creatinine greater than 1.5 mg/dl were not entered on the study, nonetheless, RNAse was significantly (P less than 0.05) associated with both BUN and creatinine. Nutritional status also had an important influence on RNAse levels as both percent weight loss and percent ideal body weight were significantly (P less than 0.05) associated with circulatory RNAse: weight loss resulted in higher RNAse levels. These results account in part for the increased RNAse levels seen in those malignant conditions such as pancreatic and lung cancer commonly associated with weight loss in advanced stage. The possibility that circulatory RNAse C determination will provide a sensitive means for assessing nutritional status in cancer patients will require prospective evaluation.

Adenocarcinoma↗
PubMed1985

Metabolic abnormalities in the cancer patient.

Many malnourished patients with cancer fail to gain weight with what appears to be adequate nutritional support. Metabolic abnormalities resulting from remote effects of the tumor on host metabolism have been postulated to increase energy requirements in such cancer patients. In the current study, 44 patients with lung cancer who had significant weight loss (16 +/- 2% of usual body weight) were studied under metabolic ward conditions. Whole body glucose production rates were significantly elevated in cancer patients compared to age-matched healthy controls. Blood glucose levels 2 hours after a standard oral glucose challenge were also significantly increased, but insulin levels were not different at this time. Fasting glucose and insulin levels were not different. Fasting plasma alanine levels were significantly decreased in these patients, while branched-chain amino acids were not different. Increased alanine flux for gluconeogenesis is likely to reflect a basic metabolic abnormality in patients with cancer and could be explained on the basis of a resistance to insulin action in such patients.

Alanine↗
PubMed1985

Critical evaluation of the role of nutritional support with chemotherapy.

Although weight loss has an adverse impact on cancer patient survival, the ability of caloric provision via total parenteral nutrition (TPN) to favorably influence outcome in chemotherapy-treated populations is not established. In randomized trials, no significant improvement in either response or survival was associated with TPN addition to chemotherapeutic treatment of adult patients with lymphoma, sarcoma, colon cancer, adenocarcinoma and small cell carcinoma of the lung, or testicular carcinoma. In two instances, TPN addition was associated with decreased survival, again raising the concern that caloric support in the absence of effective antitumor therapy might stimulate cancer growth. In any event, the hypothesis that nutritional repletion of a malnourished cancer patient receiving chemotherapy will improve clinical outcome remains to be critically tested, as studies demonstrating sequential improvement in lean body mass have not been reported. Most recently, consideration of potential mechanisms underlying the development of cancer cachexia has led to new strategies for nutritional intervention. For example, hypogonadism or low testosterone levels have been described in male patient populations with advanced cancer and correlated with weight loss and adverse outcome, leading to trial of replacement therapy with nandrolone decanoate. Similarly, the frequent identification of abnormal glucose metabolism in the patients with cancer cachexia has stimulated clinical trials with agents such as hydrazine sulfate and insulin designed to reverse the metabolic abnormality. Whether such efforts designed to alter metabolic abnormalities associated with cancer cachexia will improve clinical outcome will be determined in ongoing clinical trials.

Adult↗
PubMed1985

Significance of altered nutritional status in acquired immune deficiency syndrome (AIDS).

Severe unrelenting weight loss appears to be a major component of the clinical picture seen in the patients with Acquired Immune Deficiency Syndrome (AIDS). Weight loss has been associated with a poor prognosis for AIDS patients with Kaposi's sarcoma. Strong evidence from a variety of clinical situations indicates that malnutrition per se adversely affects the cellular immune system and the susceptibility of individuals to infectious problems. In addition, weight loss of the degree commonly seen in the AIDS population places patients at risk of death because of resultant organ dysfunction. Moreover, severe weight loss may preclude recovery from infectious complications that otherwise would not represent a lethal challenge to the host. Because even appropriately directed therapies may not be successful when used in patients with severe weight loss, it is crucial to identify the mechanism of the weight loss associated with AIDS and to rapidly initiate evaluation of agents capable of altering or reversing this potentially lethal complication.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Doxorubicin, cyclophosphamide, CCNU, and vincristine with or without cisplatinum in non-small cell lung cancer.

To evaluate the role of cisplatinum in the treatment of advanced non-small cell lung cancer, 48 patients received either a doxorubicin (adriamycin) 50 mg/m2 I.V., cyclophosphamide 300 mg/m2 I.V., lomustine (CCNU) 50 mg/m2 p.o., vincristine (oncovin) 1.2 mg/m2 I.V. (ACCO) combination or the same drugs plus cisplatinum 50 mg/m2 I.V. (PACCO) in a prospective sequential trial. No patient had received prior chemotherapy. Patients receiving the two regimens were comparable with regard to median age, performance status, histologic subtype, disease extent, and weight loss. Objective response frequency was only 5% in the initial 20 patients receiving ACCO treatment compared to a response frequency of 28% (7% complete) in the 28 patients receiving cisplatinum in the PACCO treatment arm (p less than 0.06). Patients achieving objective response lived significantly longer than nonresponders (9.1 months vs. 3.8 months, p less than 0.05). Although median survival was similar on the two regimens (6.1 months for ACCO vs. 7.6 months for PACCO), more than four times as many patients were alive after 1 year in the PACCO treatment group (24% vs. 5%). Predominant toxicity consisted of moderately severe nausea and vomiting (63% on PACCO vs. 34% on ACCO, p less than 0.05) and myelosuppression with WBC less than 3,000/mm3 occurring in the majority of patients on both regimens. These results suggest cisplatinum addition to a doxorubicin, cyclophosphamide, lomustine, and vincristine combination may be associated with increased 1-year survival in the non-small cell lung cancer patient population.

Actuarial Analysis↗
PubMed1985

Cyclophosphamide plus 5-FU versus 5-FU alone in advanced gastric carcinoma.

30 patients with advanced metastatic gastric adenocarcinoma, having a measurable indicator lesion, were randomized (1:2) to receive (intravenously) either weekly 5-fluorouracil alone (15 mg/kg) or combination treatment with cyclophosphamide (20 mg/kg) given on day 1 and 5-FU (15 mg/kg) given weekly on weeks 2-5, beginning on day 8. The combination cycle was repeated at 6-week intervals. Although the toxic effects of therapy were similar in both arms, the addition of cyclophosphamide to the single-agent 5-FU regimen did not increase either the frequency of objective response (5-FU 18%, combination 16%) or improve the median survival of patients with advanced measurable gastric carcinoma (5-FU 4.4 months, combination 5.2 months). Patients with pretreatment weight loss greater than 10% had significantly (p less than 0.05) shorter median survival (2.8 versus 5.6 months) compared to patients without weight loss.

Adenocarcinoma↗
PubMed1985

Vitamin K3 inhibition of malignant murine cell growth and human tumor colony formation.

To assess the antineoplastic potential of vitamin K compounds, the effects of vitamin K3 (menadione), vitamin K1 (phylloquinone), and warfarin on L1210 murine leukemia cell growth were studied in a flask culture system. When the cytotoxic potential of vitamin K3 was recognized, the effects of vitamin K3 on human tumor colony formation were studied in 34 tumor explants using a soft agar (clonogenic) assay system. Complete inhibition of L1210 growth in flask culture was achieved at concentrations of 200 micrograms/ml of warfarin, 75 micrograms/ml of vitamin K1, and 4 micrograms/ml of vitamin K3. Combined use of vitamin K and warfarin enhanced cytotoxicity because a concentration of 1 micrograms/ml of vitamin K3 together with 70 micrograms/ml of warfarin resulted in nearly complete inhibition of L1210 growth. Comparable inhibition of growth was seen against malignant murine cell lines in the soft agar assay system, where greater than 70% decrease in colony formation was seen with vitamin K3 at concentrations of 6.4 micrograms/ml for L1210 leukemia and 1 microgram/ml for HII4E hepatoma lines. Vitamin K3 was also cytotoxic in the same dosage range when tested in vitro against the 34 human tumor explants in the soft agar assay system. Tumor types evaluated included adenocarcinoma of the breast (16 patients), ovary (five), colon (two), stomach (two), kidney (two), and unknown primary (two); squamous cell carcinoma of the lung (two); melanoma (one), transitional cell carcinoma of the bladder (one); and hepatocellular carcinoma (one).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Hepatocellular carcinoma. Diagnostic and prognostic features in North American patients.

Diagnostic and prognostic characteristics of 121 North American patients with hepatocellular carcinoma seen in one metropolitan area over a 6-year period were assessed using multivariate analysis. Presenting symptoms commonly included abdominal pain (53%) or mass (34%), anorexia (31%), and ascites (20%); however, the ability to make an early diagnosis was complicated by a variety of unusual symptoms accounting for 25% of presentations. While cirrhosis (63%) and hepatitis B surface antigen (HBsAg) positivity (52%) were common associated findings, the majority of patients (67%) had no prior diagnosis of liver disease. Despite the vascular nature of these malignancies, percutaneous biopsy procedures performed in 66 patients provided diagnostic material in over 85% of cases with little morbidity. Histologic diagnosis was made by blind percutaneous biopsy (41 done, 83% positive), peritoneoscopy with directed percutaneous biopsy (25 done, 88% positive), laparotomy (42 done, 98% positive), or autopsy (19). Percutaneous hepatic biopsy procedures were associated with no mortality and rare bleeding (three cases). Overall median survival was only 18 weeks; multivariate analysis indicated increased bilirubin or presence of pulmonary metastases adversely influenced outcome. Unexpectedly, patients younger than 45 years of age had a significantly (P less than 0.01) greater survival (median, 40 versus 9 weeks) than did older patients with this disease. We conclude: (1) hepatocellular carcinoma can be rapidly and safely diagnosed using percutaneous biopsy procedures; (2) North American patients with hepatocellular carcinoma younger than 45 years of age have a more favorable prognosis.

Actuarial Analysis↗