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Biomedical subjects

R D Hart

Publications and source records attributed to R D Hart.

17 recordsLinked to original sources
PubMed1994

Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma.

BACKGROUND: Adjuvant chemotherapy is widely used for breast cancer and is known to extend survival. Some clinicians seek a greater survival benefit by increasing the intensity of the dose, whereas others lower it to diminish toxicity. METHODS: The Cancer and Leukemia Group B (CALGB) conducted a randomized trial of different levels of doses and dose intensity (dose per unit of time) of adjuvant chemotherapy in 1572 women with node-positive, stage II breast cancer who were assigned to three treatment groups. One group received 400 mg of cyclophosphamide per square meter of body-surface area and 40 mg of doxorubicin per square meter once every 28 days and 400 mg of fluorouracil per square meter twice every 28 days, for six cycles. Another group received 50 percent higher doses of the three drugs (600 mg, 60 mg, and 600 mg, respectively) but for only four cycles, so that the total dose was identical in these two groups but the dose intensity was higher in the first. The third group of women received half the total dose used in the other two groups and at half the dose intensity used in the second group. RESULTS: After a median of 3.4 years of follow-up, the women treated with a high or moderate dose intensity had significantly longer disease-free survival (P < 0.001) and overall survival (P = 0.004) than those treated with a low dose intensity, in three-way log-rank comparisons. However, the difference in survival between the two groups treated with a moderate or high dose intensity was not significant. These results are consistent with either a dose-response effect or a threshold level of the dose or dose intensity. CONCLUSIONS: The doses of chemotherapy used to treat breast cancer, especially early breast cancer, should not be reduced if the maximal benefit is to be achieved.

Adenocarcinoma↗
PubMed1991

Treatment of chemotherapy-induced anemia with recombinant human erythropoietin in cancer patients.

Thirty patients with chemotherapy-induced anemia were treated with recombinant human erythropoietin for 4 weeks. In this dose-escalation study, cohorts of five to eight patients were treated per dose level. The doses of erythropoietin were 25, 50, 100, 200, or 300 IU/kg/d given intravenously for 5 days each week. Of 30 patients, 15 (50%) had a greater than 10% increase of their hemoglobin (Hb) values and were considered responders. At the two highest dose levels, 11 of 13 patients (85%) responded. In the 15 responding patients, the mean Hb level increased by 1.7 g/dL from baseline compared with an average decrease of 1.5 g/dL in the previous cycles of chemotherapy without erythropoietin administration. Recombinant human erythropoietin is effective in ameliorating chemotherapy-induced anemia when administered in adequate doses.

Adult↗
PubMed1987

Pilot trial of prolonged continuous-infusion 5-fluorouracil and weekly cisplatin in advanced colorectal cancer.

Thirty-five patients with previously untreated, advanced, measurable metastatic colorectal carcinoma were treated with a 12-week course of continuous 5-fluorouracil (5-FU) and weekly cisplatin. Twenty of 32 evaluable patients responded (five complete and 15 partial responses), for an overall response rate of 63% (90% confidence limits, 43%-75%). Toxicity was generally mild and reversible and included mucositis (40%), painful erythema of the palmar and plantar skin (30%), diarrhea (21%), nausea and vomiting (15%), and leukopenia (6%). One patient died of sepsis secondary to mucositis and myelosuppression. This program is a well-tolerated outpatient regimen for metastatic colorectal carcinoma. The response rate is higher than expected for 5-FU and cisplatin and suggests clinical therapeutic synergism at this dose rate and schedule.

Adult↗
PubMed1984

Lipoamide dehydrogenase deficiency with primary lactic acidosis: favorable response to treatment with oral lipoic acid.

An 8-month-old boy with severe lactic acidosis was found to have lipoamide dehydrogenase deficiency. Treatment with thiamine, biotin, bicarbonate, protein restriction, and ketogenic diet failed to alleviate the lactic acidosis. Oral administration of lipoic acid 25 to 50 mg/kg produced dramatic improvement in lactic and pyruvic acidemia, which has continued for 2 years and which has been accompanied by clinical improvement.

Acidosis↗
PubMed1984

Experimental and clinical activity of mitomycin C and cis-diamminedichloroplatinum in malignant mesothelioma.

Little information is available regarding the effectiveness of chemotherapeutic agents in malignant mesothelioma. Human malignant mesothelioma specimens from two patients were successfully transplanted and maintained in homozygous nude mice. Screening of chemotherapeutic agents revealed that cisplatin was the most active single agent in one line, and mitomycin C in the other. The combination of mitomycin C and cisplatin, however, was the most effective regimen for both lines of xenografted human mesothelioma. Based on these results in nude mice, a clinical trial of mitomycin C and cisplatin was undertaken. Four of 12 patients showed objective response (one complete and three partial). These clinical results support the usefulness of the nude mouse model for malignant mesothelioma.

Aged↗
PubMed1982

Methyl-GAG in patients with malignant neoplasms: a phase I re-evaluation.

Methyl-GAG was given to 71 patients with advanced malignancies as a weekly brief infusion (30-120 minutes) or as a biweekly 24- or 120-hour infusion. Mucositis (stomatitis, pharyngitis, esophagitis, and, rarely, inflammation of other mucous membranes) was dose-limiting in all three schedules. Generalized fatigue, malaise, myalgia, dysesthesias, nausea, and vomiting were more frequent in the brief-infusion schedule. Myelosuppression was mild and not dose-related. Fever, ventricular arrhythmias, skin rash, tender swelling of the palms, neuropathy, and paralytic ileus were rare. Toxicity was increased in patients with renal insufficiency or "third-space" fluid but was not increased by hepatic dysfunction. Cumulative and overlapping toxicity was evident only in the weekly schedule. Higher doses of methyl-GAG were tolerated when the duration of infusion was increased. The recommended doses for phase II trials are 700 mg/m2 weekly as a 1-2 hour infusion, 850 mg/m2/24 hours biweekly, and 1500 mg/m2/120 hours biweekly. Therapeutic effects were seen in all schedules and included objective responses in colon carcinoma (one of 13 patients), renal cell carcinoma (one of nine), and Hodgkin's lymphoma (one of two) and objective improvements in esophageal carcinoma (one of three), endometrial carcinoma (two of two), and leiomyosarcoma (one of three).

Adult↗
PubMed1981

One-day VATH (vinblastine, Adriamycin, thiotepa, and Halotestin) therapy for advanced breast cancer refractory to chemotherapy.

Twenty-nine postmenopausal patients with metastatic breast cancer refractory to conventional combination chemotherapy underwent treatment with a combination of vinblastine, Adriamycin, thiotepa, and Halotestin given once every 21 days. Thirteen patients (45%) responded with a greater than 50% regression of measurable tumor. Responses occurred in nine of 12 patients (75%) with visceral dominant disease and were recognized in four of 15 (27%) with osseous dominant disease (another 5 improved for a total improvement of 60%). The median duration of response was 11 months. The median survival times were 16 months for responders and eight months for those with progressive disease. Response rate was not affected by age, number of years after menopause, number of metastatic sites involved, or number of systemic treatment modalities previously used, but may have been adversely affected by late stage at original diagnosis, short time from diagnosis, poor response to primary chemotherapy, and dose modification. This combination of drugs is a convenient, tolerable, and effective regimen for treating breast cancer refractory to primary chemotherapy regimens currently in use.

Adult↗
PubMed1978

Vinblastine, adriamycin, thiotepa, and halotestin (VATH): therapy for advanced breast cancer refractory to prior chemotherapy.

Nineteen postmenopausal patients with metastatic breast cancer refractory to conventional combination chemotherapy were treated with monthly cycles with the combinations of vinblastine, adriamycin, thiotepa and halotestin. Ten patients (52%) responded with a greater than 50% regression of measurable tumor. The median duration of response was 11.5 months, with 5/10 patients still responding at a mean follow-up of 10 months. Only 2/10 responders have died with a mean follow-up of 13.8 months. In contrast, 8/9 nonresponders have died (median survival 6.0 months). Response to therapy was neither influenced by site of disease, time interval from diagnosis to primary chemotherapy nor duration of response to primary chemotherapy. No patient was hospitalized because of drug induced toxicity. This combination of drugs is a tolerable effective regimen for patients relapsing after adjuvant chemotherapy or after primary combination chemotherapy for grossly metastatic disease.

Adult↗
PubMedDate not supplied

Determination of methylglyoxal-bis(guanylhydrazone) in body fluids by ion-pair chromatography.

Methylglyoxal-bis(guanylhydrazone), Methyl-G, is a potent antineoplastic agent currently undergoing Phase l clinical trials. Serum, ascitic and pleural fluids, and urine are deproteinized with methanol, supernatant is evaporated, residue is redissolved in the eluent, lipids are removed with carbon tetrachloride, and an aliquot of the aqueous layer injected into the chromatograph. Ethylglyoxal-bis(guanylhydrazone) (Ethyl-G) is the internal standard. The mobile phase is a mixture of an aqueous buffer (containing 0.004 M heptane and pentane sulfonic acid, 90%:10%, buffered to pH 3.5) and methanol (68%:32%). The ion-pair complex is retained on a micro Bondapak C18 column, eluted with a flow of 2.0 mL/min. Absorbance is measured at 280 nm. Detectability: 30 ng/mL (0.11 micro M) in serum, ascitic and pleural fluids, 300 ng/mL (1.1 micro M) in urine. Calibration curves (peak height ratios of Methyl-G/Ethyl-G plotted against known drug concentrations) were linear in the 0.1-30 microg/mL range. Correlation coefficinets were 0.999; coefficients of variation for reproducibility were less than 5%. Residual blood levels of Methyl-G persist for several days. Methyl-G was found to pass into ascitic fluid.

Ascitic Fluid↗
PubMedDate not supplied

Initial clinical study with N-(phosphonacetyl)-L-aspartic acid (PALA) in patients with advanced cancer.

Thirty-seven patients with inoperable malignancies were given 75 courses of N-(phosphonaceteyl)-L-aspartic acid (PALA). Twenty-seven of these patients received PALA as a continuous iv infusion over 24 hours at dose levels ranging from 500 to 10,500 mg/m2 of estimated body surface area. In addition, ten patients were given PALA by continuous iv infusion over 120 hours at total doses ranging from 4000 t0 8700 mg/m2. The dose-limiting toxic effects occurred in the skin (erythema, vesiculation, and bullae) and gastrointestinal mucosa (oral pain, cheilosis, oral mucosal ulceration, diarrhea, and hematochezia). Toxic reactions seemed more pronounced in patients with third-space fluid compartments. Myelosuppression was severe only in patients with pre-existing marrow dysfunction from neoplastic infiltration. No renal, hepatic, cardiac, or neurologic toxicity was seen. No cumulative toxic effects were evident in 14 patients who received repeated courses of PALA at 21-day intervals. For patients without third-space fluid, 8700 mg/m2/24 hours or 6500 mg/m2/120 hours were well-tolerated doses. One patient with chondrosarcoma had a partial response lasting 5 months.

Adult↗