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Biomedical subjects

D R Budman

Publications and source records attributed to D R Budman.

At least 73 records · Page 4Linked to original sources
PubMed1990

A feasibility study of intensive CAF as outpatient adjuvant therapy for stage II breast cancer in a cooperative group: CALGB 8443.

In preparation for a national Phase III study of dose and dose intensity in the treatment of node-positive, Stage II adenocarcinoma of the female breast, CALGB instituted a pilot study of intensive intravenous outpatient CAF (cyclophosphamide, Adriamycin, 5-fluorouracil) for four months. This study was designed to give full doses of drugs without dose reduction for hematologic toxicity. In order to evaluate the feasibility of physician and patient compliance with a potentially toxic therapy, a multi-institution pilot study was performed. This protocol demonstrated that a cooperative group could deliver toxic drug doses to outpatients with a median of 98% of cyclophosphamide, 97% of Adriamycin (doxorubicin), and 91% of 5-fluorouracil administered on schedule. Major side effects, as expected, were leukopenia, nausea, and vomiting. Disease-free survival is at least equivalent to that observed in previous studies.

Adenocarcinoma↗
PubMed1989

Production of autoantibodies by CD5-expressing B lymphocytes from patients with chronic lymphocytic leukemia.

CD5-expressing B lymphocytes from patients with selected chronic lymphoproliferative disorders were used to determine whether monoclonal populations of CD5+ human B cells produce autoantibodies. CD5+ B cells from 19 patients with chronic lymphocytic leukemia (CLL) and one with diffuse well-differentiated lymphocytic lymphoma (DWDL) were cultured, with and without mitogenic stimulation, to obtain Ig from these cells. 17 of the 20 samples produced Ig in vitro. mAb from nine of the 17 patients were reactive with either IgG, ssDNA, or dsDNA. In every instance, the autoantibodies displayed monotypic L chain usage that correlated precisely with the L chain expressed on the CD5+ leukemic B cell surface. These monoclonal autoantibodies varied in their degree of antigenic specificity; some were quite specific, reacting with only one antigen, whereas others were polyspecific, reacting with two or all three autoantigens tested. Three features distinguish these autoantibodies from those observed in prior studies of CD5+ B cells. First, they are clearly the products of monoclonal populations of CD5+ cells; second, several react with dsDNA, a specificity not previously reported and often seen in association with significant autoimmune disorders; and third, two of the monoclonal autoantibodies secreted by the CD5+ clones were of the IgG class. Although not all of the Ig-producing, CD5-expressing clones elaborated mAbs reactive with the autoantigens tested, greater than 50% did. It is possible that with a broader autoantigenic panel or with larger quantities of CLL/DWDL-derived Ig, even more autoantibody-producing clones might be identified. These studies may have important implications for the antigenic specificity of subsets of human B lymphocytes as well as for lymphoproliferative and autoimmune disorders in general.

Antibody Specificity↗
PubMed1989

Trisomy 20 in acute myelogenous leukemia.

A patient with acute myelomonocytic leukemia was found to have trisomy 20 in his bone marrow cells. The patient achieved a complete response to standard antileukemic therapy. The literature is reviewed in regard to this abnormality.

Aged↗
PubMed1988

Pharmacokinetic and phase I evaluation of esorubicin (4'-deoxydoxorubicin) by continuous infusion over forty-eight hours in patients with leukemia.

Sixteen patients with previously treated acute nonlymphocytic leukemia or chronic myelogenous leukemia in blast crisis were given one to three courses of esorubicin by continuous infusion over 48 h. Dosage levels extended from 35 to 85 mg/m2. Four patients showed partial responses of short duration. Nonhematological toxicity observed at dosages of 55 to 85 mg/m2 were mucositis, diarrhea, skin rash, transaminitis, nausea, vomiting, and cardiac dysfunction. One patient receiving 85 mg/m2 developed acute florid congestive heart failure within hours of administration of the drug. Pharmacokinetic analysis revealed large interpatient variation in plasma drug levels. At the end of infusion, plasma decay of esorubicin was rapid initially but slow thereafter, with a terminal half-life of 20 to 54 h. The metabolite 4'-deoxy-13-hydroxydoxorubicin reached significant plasma levels. Total body clearance, renal clearance, volume of distribution at steady state, and mean residence time show little variation during dose escalation for both esorubicin and 4'-deoxy-13-hydroxydoxorubicin. Urinary excretion of esorubicin and 4'-deoxy-13-hydroxydoxorubicin accounted for 10.5 and 1.5%, respectively, of the administered dose.

Doxorubicin↗
PubMed1988

Effect of tetrahydrouridine on the clinical pharmacology of 1-beta-D-arabinofuranosylcytosine when both drugs are coinfused over three hours.

When 1-beta-D-arabinofuranosylcytosine (ara-C), 25 mg/m2, is infused over 3 h together with tetrahydrouridine (THU) at 10 to 350 mg/m2 to heavily pretreated patients with solid tumors, Michaelis-Menten type kinetic values are observed with leveling off of delta area under the curve, delta ara-C levels at 3 h, and delta total body clearance after 150 mg/m2 of THU. When the ara-C dose was increased to 50, 75, and 100 mg/m2 coinfusion of 250 or 350 mg/m2 of THU significantly increased plasma ara-C at peak and area under the curve. In contrast, total body clearance and volume of distribution decreased significantly. At 100 mg/m2 of ara-C coinfused with high doses of THU, i.e., at 350 mg/m2, the pharmacokinetics of plasma ara-C was changed from a biphasic decay of plasma ara-C at peaks (control) to a curve similar or identical to a monophasic curve, indicating that THU not only inhibits deamination but also changes the distribution of ara-C. This combination provides plasma ara-C levels (greater than or equal to 10 microM) comparable to high dose ara-C at 1 g/m2. Such plasma ara-C levels are considered to be sufficient for saturation of the kinases catalyzing the production of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate. This reduced ara-C dose necessary to achieve saturation of kinases also reduces plasma 1-beta-D-arabinofuranosyluracil levels substantially. Toxicity of this combination was predominantly confined to bone marrow and gastrointestinal toxicity.

Adult↗
PubMed1987

Combination trial of subcutaneous interferon alfa-2b and oral cyclophosphamide in favorable histology, non-Hodgkin's lymphoma.

Patients with follicular non-Hodgkin's lymphoma (NHL) respond well to chemotherapy but frequently relapse and progress with conversion to more aggressive histology lymphomas. In a prior Cancer and Leukemia Group B (CALGB) trial, oral cyclophosphamide, given as a single agent, was found to be equivalent to a five-drug regimen in remission induction in patients with follicular NHL who had not received prior chemotherapy. Recently, interferon alfa-2b (Intron A; Schering Plough) has been demonstrated to elicit complete or partial responses in up to 50% of patients with nodular NHL who had received prior chemotherapy. In the current CALGB pilot trial, oral cyclophosphamide (100 mg/m2 daily) combined with interferon alfa-2b (2 X 10(6) IU/m2 s.c. on alternate days) is being evaluated, both in previously treated and untreated patients with stage III or IV follicular NHL, for toxicity, safety and efficacy in remission induction. A total of 68 patients have been entered into this study. Four patients are ineligible on pathology review, and 60 have on-study data currently available. Forty-one (60%) had not received prior chemotherapy and 19 (32%) had previously received some form of chemotherapy. Leukopenia was found to be the single, most common toxicity experienced by all patients. Previously untreated patients experienced leukopenia of less than 2,000 WBC/microliter at a significantly higher rate (53% versus 14%) than a similar patient population receiving oral cyclophosphamide as a single agent in the prior CALGB trial. Leukopenia was found to be promptly reversible, however, by dose suspension or adjustment, and other toxicities were demonstrated to be mild and tolerable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

High grade dysplasia in Crohn's colitis characterized by flow cytometry.

A patient with Crohn's ileocolitis had high grade dysplasia. Preoperative evaluation of colonoscopic biopsies by flow cytometry demonstrated aneuploidy, a marker of malignancy. In the surgical specimen, however, carcinoma was not demonstrated despite extensive sampling. The detection of abnormal DNA content in this premalignant lesion suggests a useful role for this technique in selecting those patients with inflammatory bowel disease at risk for carcinoma.

Aneuploidy↗
PubMed1987

Flow cytometry. A new technique in the diagnosis of malignant ascites.

The diagnosis of peritoneal carcinomatosis is often dependent on the finding of malignant cells in ascitic fluid analysis by a trained cytologist. Other methods are needed to increase the current diagnostic yield of 60-90%. Abnormal DNA content is characteristic of most malignancies. In an attempt to detect aneuploidy, we used high-resolution DNA histogram analysis with fluorescent DNA-specific stains and flow cytometry to evaluate 33 ascitic fluid samples. Of 13 patients with malignant ascites, aneuploidy was demonstrated in 10. Six patients with proven peritoneal carcinomatosis and normal cytologic examination had abnormal DNA histograms. DNA quantitation and cytologic examination agreed in 24 of 33 cases. These findings suggest that flow cytometry is a rapid and useful technique in the diagnosis of malignant ascites. The presence of aneuploidy in cells from ascitic fluid is highly suspicious for peritoneal carcinomatosis and suggests the need for further evaluation for malignancy.

Aneuploidy↗
PubMed1987

DNA content in Barrett's esophagus and esophageal malignancy.

Barrett's esophagus is a premalignant condition; endoscopic surveillance is often performed to search for early adenocarcinoma of the esophagus. In an attempt to detect early changes of malignancy, we have added the use of flow cytometry to routine endoscopic surveillance procedures. DNA histograms were generated from biopsy samples by utilizing a specific DNA fluorochrome (4',6-diamidino-2-phenylindole) and flow cytometry. Sixty-three samples from patients with esophagitis, Barrett's esophagus, and esophageal malignancy were analyzed. An abnormal DNA histogram (aneuploidy) was detected in 79% of esophageal malignancies. In addition, aneuploidy was detected in seven patients with Barrett's esophagus, two of whom had dysplasia. DNA quantification with flow cytometry may be a useful adjunct in screening patients with Barrett's esophagus for early malignant change.

Adenocarcinoma↗
PubMed1986

Clinical pharmacology of vinzolidine.

Vinzolidine (VZL), a new semisynthetic vinca alkaloid, was studied by using 3H-labeled VZL administered PO in four patients. At single doses from 1.5 to 36.5 mg/m2 (0.034-0.919 mg/kg) radioactivity was rapidly absorbed with a half-life of absorption of 1 h and a peak at 4 h. Plasma decay of radiolabel followed a biphasic pattern with an alpha half-life of 10.48 h and a beta half-life of 172 h. The apparent plasma clearance was dose-dependent. The total radiolabel recovered was 52.9% +/- 11.4% of the administered label, with 90% in the feces. HPLC analysis revealed that in all extracted plasma, urine, and feces the predominant material was unchanged VZL. Several metabolites were observed but not identified.

Dose-Response Relationship, Drug↗
PubMed1986

Flow cytometry of peritoneal washings in gynecologic neoplasia.

A prospective, double blind study was initiated to compare flow cytometry to cytopathology in detecting malignant cells within peritoneal washings. Deoxyribonucleic acid (DNA) histograms were generated using 4',6-diamidino-2-phenylindole (DAPI) as a DNA fluorochrome. Evaluation of these data revealed a correlation of 84.5% with the cytologic findings. Two specimens demonstrated euploidy in the presence of cytologically malignant cells (false negative), 28 of 128 specimens (21.8%) manifested aneuploidy with negative cytologic findings (false positive). Further evaluation of this latter subgroup revealed 22 of the 28 to possess unequivocal histologic evidence of malignancy, thus yielding an actual false positive rate of 4.7%. This preliminary study demonstrates that flow cytometry is a highly sensitive, accurate, and analytic method for the detection of malignant cells within peritoneal washings and that it may augment the cytologic examination. However, additional comparative studies are necessary to conclusively demonstrate its apparent diagnostic potential.

Cell Nucleus↗
PubMed1986

Comparative cost analysis of home and hospital treatment.

A comparative study evaluating home and hospital treatment for terminal cancer patients is reported. Home care was provided by a comprehensive home care program, the Don Monti Home Oncology Medical Extension (H.O.M.E.). A multispecialty team including an oncologist, oncology nurse, social worker, dietitian and technologist is transported to the home in a medically-equipped van to render treatment. Services provided include physical assessments, pain control, chemotherapy and transfusion administration, psychosocial support, nutrition education and bereavement counseling. Two-hundred eighteen patients were entered of which 174 were treated at home and 44 in the hospital. Patients were comparable in age, diagnosis, sites of metastases, prior treatment and Karnofsky status. Both groups received similar supportive care either at home or in the hospital. Cost analysis of home and hospital care revealed a per diem cost benefit of $256.00 for home treatment. Comprehensive home treatment provided by a multi-specialty team can deliver effective care with medical and financial benefits to terminal cancer patients.

Cost Control↗
PubMed1985

Pharmacokinetics of low-dose 1-beta-D-arabinofuranosylcytosine given by continuous intravenous infusion over twenty-one days.

The pharmacokinetic parameters of low dose 1-beta-D-arabinofuranosylcytosine (ara-C) infusions were studied in 11 patients, 6 males and 5 females, with a mean age of 68.5 +/- 13.8 (SD) years. The drug was infused to 4 patients with pre-leukemia (refractory anemia with excess blasts), 5 patients with acute myelogenous leukemia, and 2 patients with secondary leukemia due to chemotherapy, at a dosage of 20 mg/m2/day over 21 days. The patients' blood and urine were analyzed for ara-C content by radioimmunoassay. Mean steady state plasma levels of 7.7 +/- 4.7 ng/ml (31.7 +/- 19.3 nM) (n = 189) and a range 0.6 (2.5 nM) (lower limit of assay) to 29.7 ng/ml (122.1 nM), with significant inter- and intra-patient variations, were reached within about 2.7 h. The plasma levels of ara-C decreased rapidly, with a t1/2 alpha of about 12 min following discontinuation of the infusion, followed by a very slow t 1/2 beta of about 19 h. Other parameters (mean values of 10 or 11 patients) were: area under the curve, 182.1 +/- 64.8 ng X day/ml; total body clearance, 188.7 +/- 54.8 liters/h; renal clearance, 3.1 +/- 1.4 liters/h; volume of distribution at steady state, 53,913 +/- 17,626 liters; and recovery of ara-C in urine, 1.43 +/- 0.69% (n = 226) of daily administered ara-C. A linear relationship was observed with administered dose when the mean plasma levels of our study were compared with the ones reported for conventional ara-C infusions. Plasma clearance was comparable to that observed in conventional dose, when the observed values were extrapolated to the dose administered in this study.

Aged↗