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Biomedical subjects

R T Chlebowski

Publications and source records attributed to R T Chlebowski.

85 records · Page 5Linked to original sources

Metabolism of methotrexate in man after high and conventional doses.

Methotrexate has been found to be extensively metabolized to 7-hydroxymethotrexate in patients receiving conventional doses (less than 10 mg/kg) and high doses (greater than 10 mg/kg). Twelve hours after administration, plasma levels of this metabolite in several patients treated with low doses exceeded those of methotrexate. No 7-hydroxymethotrexate was found in CSF after CNS administration of methotrexate; however, small amounts of the metabolite was found in the CSF after intravenous high dose infusion. We conclude that methotrexate is significantly metabolized in man at all doses used clinically.

Chromatography, High Pressure Liquid↗

Survival of patients with metastatic breast cancer treated with either combination or sequential chemotherapy.

One hundred twenty-one patients with metastatic adenocarcinoma of the breast were randomized to concurrent combination therapy or single-drug chemotherapy administered sequentially. Although response frequency and duration of response were significantly increased in patients receiving the combination regimen, survival was not significantly prolonged when compared to those receiving sequential treatment. For the 69 patients free of liver metastasis, median survival was comparable in both treatment arms (14.4 months sequential versus 12.8 months combination). These results indicate that a large subset of patients with metastatic breast cancer may benefit from less aggressive therapeutic regimens. Furthermore, these results illustrate that conclusions of chemotherapy trials in breast cancer based only on response frequency and duration of response represent preliminary results subject to change when final survival information becomes available.

Adenocarcinoma↗

Adriamycin (doxorubicin) cardiotoxicity: a review.

Adriamycin (doxorubicin hydrochloride) is an antineoplastic agent effective against a wide range of malignant conditions, although cardiac toxicity, especially dose-dependent cardiomyopathy, limits its long-term use. Previous mediastinal radiation therapy or left ventricular dysfunction and advanced age increase the risk of this complication developing. Unfortunately, there is no readily available, noninvasive method that can predict Adriamycin-induced congestive heart failure (CHF). However, both endomyocardial biopsy and radionuclide ejection-fraction measurement are promising techniques which may soon permit selection of patients who can safely receive this drug. At present, Adriamycin-induced CHF can best be prevented by limiting the total dose as follows: 400 to 450 mg per sq meter following mediastinal radiation and 500 to 550 mg per sq meter for patients without other significant risk factors. Consideration of dose-response data and use of a weekly schedule may soon permit the administration of Adriamycin for long-term antineoplasm therapy.

Age Factors↗

Cyclophosphamide (NSC 26271) versus the combination of adriamycin (NSC 123127), 5-fluorouracil (NSC 19893), and cyclophosphamide in the treatment of metastatic prostatic cancer: a randomized trial.

Twenty-seven patients with a diagnosis of metastatic adenocarcinoma of the prostate were treated in a randomized, prospective trial with either Cyclophosphamide or a combination of Adriamycin, 5-Fluorouracil, and Cyclophosphamide. Doses were either Cyclophosphamide alone (800-1200 mg/m2 iv q 3 weeks) or Cyclophosphamide (150-200 mg/m2 po Day 3-6) plus 5-FU (400-500 mg/m2 iv Day 1, 8) plus Adriamycin (30-50 mg/m2 iv Day 1) given as a 4 week treatment cycle. Patients with compromised bone marrow reserve initially received the lower dose level. Objectively stable disease as defined by a modification of the National Prostatic Cancer Project criteria was seen in 53% of the 15 Cyclophosphamide treated patients and in 50% of the 12 combination treated patients. Survival was not significantly different in the two arms. However, the survival of patients responding to Cyclophosphamide was significantly longer than that of patients responding to the combination (median 18.6 months versus 8.1 months, p less than 0.05). Gastrointestinal and hematologic toxicity was moderate with both regimens. Therefore, in the present study, Cyclophosphamide alone was as effective as the combination of Cyclophosphamide, 5-FU and Adriamycin for patients with disseminated prostatic carcinoma. The moderate hematologic toxicity noted with both regimens suggests further evaluation of drug combinations utilizing higher dosages of active agents in this disease.

Adenocarcinoma↗

Metabolic response to chemotherapy in colon cancer patients.

The goal of this investigation was to identify the metabolic abnormalities in a group of colon cancer patients before and during 5-fluorouracil chemotherapy. Twenty-two colon cancer patients were prospectively enrolled into a Clinical Research Center for measurement of counter regulatory hormones, fasting hepatic glucose production (HGP), intravenous glucose tolerance test, plasma leucine appearance (LA), and leucine oxidation (LO). Both the cancer group and the normal volunteers were matched for nutrition status (109 +/- 5% of ideal body weight vs 104 +/- 4%, mean +/- SEM, respectively) and history of weight loss (6.3 +/- 2.6 kg vs 4.4 +/- 4.8). Plasma growth hormone was significantly elevated in the colon cancer patients (3.22 +/- 0.62 ng/mL vs 0.73 +/- 0.18, p < .05) despite the fact that insulin-like growth factor-1 levels were not different. Plasma glucose, insulin, cortisol, glucagon, epinephrine, and norepinephrine levels were not significantly different than those of the normal volunteers. Fasting HGP rates were slightly but not significantly elevated in the group of colon cancer patients compared with the normal volunteers (2.09 +/- 0.11 mg/kg per minute vs 1.79 +/- 0.10, p = .10). Plasma LA was not significantly elevated in the colon cancer group (63.3 +/- 3.0 mumol/kg per hour vs 57.7 +/- 4.2; p = .25). Five days of continuous 5-fluorouracil chemotherapy was associated with a significant elevation in both the fasting glucose level (97 +/- 3 mg/dL vs 106 +/- 5, p < .05), and HGP (2.09 +/- 0.11 mg/kg per minute vs 2.27 +/- 0.10; p < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Colonic Neoplasms↗

Treatment of advanced gastric carcinoma with 5-fluorouracil: a randomized comparison of two routes of delivery.

Fifty-seven patients with advanced gastric carcinoma were randomized to receive 15 mg/kg/week of 5-fluorouracil by either the iv or oral route. Toxic effects of treatment included nausea and vomiting (40% with the oral route versus 35% with the iv route) and myelosuppression, with a wbc count of less than 4000/mm3 (28% with the oral route versus 32% with the iv route). The frequency of partial response was 12% (three of 25 patients) for the oral route and 16% (five of 32 patients) for the iv route. Only two of 36 patients with liver metastases responded. No advantage was seen for the oral versus the iv route of 5-fluorouracil in the treatment of advanced gastric carcinoma.

Administration, Oral↗

Randomized comparison of two combination chemotherapy regimens containing doxorubicin in patients with metastatic breast cancer: a Western Cancer Study Group trial.

Ninety-six patients with metastatic breast cancer were entered in a prospectively randomized trial comparing a five-drug doxorubicin (Adriamycin)-containing regimen given in two different schedules. Both regimens included cyclophosphamide, methotrexate, 5-FU, prednisone, and doxorubicin. On one schedule, referred to as "combination" treatment, doxorubicin was given every 21 days and cyclophosphamide was given daily. On the less intensive "fixed-rotation" schedule, doxorubicin was given on alternative cycles every 42 days and cyclophosphamide was given for 21 days of the 42-day cycle. Response frequency and survival were comparable among patients receiving either regimen. Significantly less (P < 0.05) nausea and leukopenia occurred on the fixed-rotation schedule. Therefore, similar therapeutic benefit along with decreased toxicity was obtained by use of combination chemotherapy involving doxorubicin and cyclophosphamide given in the less intensive schedule.

Antineoplastic Agents↗

Long-term effects of early nutritional support with new enterotropic peptide-based formula vs. standard enteral formula in HIV-infected patients: randomized prospective trial.

Despite association with adverse clinical outcome, human immunodeficiency virus (HIV)-associated malnutrition has been relatively refractory to conventional nutrition management. Consequently, a prospective randomized trial was conducted to evaluate a new peptide-based enteral formula (NEF) in contrast to a standard enteral formula (SEF) in patients with HIV infection. Eighty early-stage largely asymptomatic patients were randomized into a dietary regimen supplemented with either a ready-to-feed NEF (18.7% protein, 65.5% carbohydrate, 15.8% fat; 1.28 kcal/ml) or SEF (14% protein, 55% carbohydrate, 31% fat; 1.06 kcal/ml). Patients received 2-3 8-oz cans of the NEF or SEF supplement per day for 6 mo. Parameters evaluated at 0 (baseline), 3, and 6 mo included adherence, weight change, anthropometric measurements, serum biochemical indices, gastrointestinal symptoms, physical performance, and intercurrent health events (including hospitalizations). For the 56 evaluable patients, those supplemented with NEF maintained their body weight significantly (p = 0.04) better, had significantly (p = 0.03) more stable triceps skin-fold measurements, and had significantly (p = 0.04) lower blood urea nitrogen than patients consuming the SEF supplement. Consumption of the NEF supplement was also associated with significantly reduced hospitalizations during the 3- to 6-mo evaluation period (p = 0.02). The NEF supplement was well tolerated and did not result in untoward clinical effects. These data suggest that supplemental use of an NEF provides superior nutritional management compared with an SEF for patients with early-stage HIV infection.

Adolescent↗

Factors influencing nurses' breast cancer control activity.

A needs assessment survey of 2800 registered nurses in a major metropolitan area was performed to identify: (1) knowledge about breast cancer risk and screening; (2) attitudes toward cancer prevention and early detection; (3) practice of breast cancer control activities; and (4) perceived barriers to practice. Responses from 1,117 nurses were obtained. Nurses reported knowledge deficits regarding breast cancer risk factors (36%) and signs and symptoms of breast cancer (35%). Compared with physicians, nurses reported more favorable attitudes toward cancer prevention and early detection. More than 85% of nurses believed that nursing had a role in breast cancer screening and early detection, and 60% believed that nursing activity in this area would increase in the future. The most common breast cancer control activity performed by nurses was assessment of breast cancer history (61%). The least frequent early detection activity was performance of a breast examination (27%). Approximately 50% of nurses taught women about breast self-examination and mammography. Common barriers limiting practice included work setting obstacles (64%), knowledge and skill deficits (57%), lack of patient education materials (51%), uncertainty about nurses' versus physicians' role in breast cancer control (52%), and time constraints (42%). It is important to note that 70% of nurses viewed themselves as resources for breast cancer screening and early detection, particularly in reducing fears and misconceptions about cancer, assessing and informing patients about individual cancer risk, and developing a plan for screening. Based on the results of this survey, nurses may represent a key potential resource for implementing breast cancer screening and early detection activities if barriers limiting practice can be overcome.

Adult↗