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Biomedical subjects

R S Benjamin

Publications and source records attributed to R S Benjamin.

252 records · Page 14Linked to original sources
PubMed1976

Kinetic response of human lymphoid cells to adriamycin-DNA complex in vitro.

The lysosomotropic agent adriamycin-DNA complex was analyzed for its effect on cell cycle progression of human lymphoid cells in culture by means of pulse cytophotometry. Complexing to DNA slightly reduced the perturbation effects previously reported for adriamycin alone. The major kinetic response was a G2 block, the magnitude and duration of which was dependent on drug concentration and duration of treatment. When high drug concentrations were maintained for a prolonged period of time, an additional, completely reversible block in G1 phase or at the G1-S boundary was observed, accounting for two-step G2 accumulation curves. Cell age markedly influenced the magnitude of G2 accumulation in that treatment of cells in S and early G2 phase was most effective.

Cells, Cultured↗
PubMed1976

Role of DTIC (NSC-45388) in the chemotherapy of sarcomas.

DTIC was one of the first of several new agents evaluated by the Southwest Oncology Group (SWOG) and the M.D. Anderson Hospital and Tumor Institute (MDAH) in the therapy of adult patients with metastatic sarcomas. It yielded an overall response rate of 17%. This is similar to that seen in a review of 138 patients who represent the total number reported in either published or unpublished data. The subsequent addition of DTIC to adriamycin in several studies carried out at the MDAH and in the SWOG has increased the complete and partial remission rate over that seen with adriamycin alone, and more importantly has increased remission duration and survival. DTIC is currently used in combination with adriamycin in the first-line therapy of patients with metastatic sarcomas and should be considered for patients who have relapsed on primary therapy not including DTIC.

Clinical Trials as Topic↗
PubMed1975

Adriamycin: a new effective agent in the therapy of disseminated sarcomas.

Thirty-six patients with disseminated sarcomas were treated with adriamycin according to an intermittent single high-dose schedule based on our prior pharmacologic observations. The dose of 60 mg/M2 IV q 3 weeks was reduced 50-75% in the presence of liver disease. Complete remission occurred in 9%, parital remission in 32%, and improvement in 21% for median durations of 37, 18, and 15 weeks, respectively. Survival was prolonged in responding patients. Hematologic suppression was mild in the absence of liver disease or prior extensive radiotherapy. Congestive heart failure, a well-known long-term complication of therapy with anthracycline drugs, occurred in two out of four patients who had cumulative doses of 600 mg/M2 or more. Mucous membrane toxicity was not observed. Adriamycin is an effective new agent in the therapy of disseminated sarcomas and can be used with relative safety by following pharmacologic principles.

Adolescent↗
PubMed1974

Adriamycin.

Explore the source record for details and available documents.

Doxorubicin↗
PubMedDate not supplied

New chemotherapeutic strategies for soft tissue sarcomas.

Advanced soft-tissue sarcomas are still incurable in the vast majority of patients. The currently available standard methods of treatment such as surgery, radiation therapy, and chemotherapy have a very modest impact on the natural history of advanced soft tissue sarcomas. Nevertheless, until new strategies become widely available and applicable to this disease, we are obligated to optimize the current resources and make the best use of these modalities. We discuss the approaches of standard chemotherapy used in a dose-intensive fashion (especially in high-risk patients at an earlier stage), attempts to find new drugs with activity in this disease, and tests of the concepts of anti-angiogenic and differentiation therapy. To improve cure rates, patients and physicians must be encouraged to participate in multidisciplinary clinical trials.

Antineoplastic Agents↗
PubMedDate not supplied

Clinical pharmacology of intramuscularly administered L-asparaginase.

Clinical pharmacology of L-asparaginase was compared by intramuscular and intravenous injections in 12 patients with metastatic cancer or leukemia. Following a single intramuscular injection at the gluteal site of L-asparaginase (10,000 IU/m2), the enzyme appeared in plasma as measured initially at 1 hour, but plateau levels were not reached in plasma until 14 to 24 hours after drug administration. The peak plasma level was 1.12 IU/ml, only one fourth of that seen when L-asparaginase was given intravenously at equal doses. However, the enzyme level decrease in the plasma after intramuscular injections was slower, with a half-life ot 46 hours, compared to 7 to 28 hours for intravenously administered drug. The apparent volume of distribution indicated that the intravenously injected enzyme was mostly distributed in plasma, whereas the intramuscularly injected enzyme yielded a much larger volume of distribution (63 versus 245 ml/kg). In addition, only 19 per cent of the intramuscularly injected dose was in plasma, and the area under the curve (C X t) was only 1/24 that by intravenous route (20 versus 487 IU/ml.hr). No enzyme was measurable in patients' urine samples collected for three days after intramuscular injections of the enzyme, and only a trace (less than 1 per cent) of the enzyme was detected in urine after intravenous administration.

Asparaginase↗
PubMedDate not supplied

Assessment of anthracycline cardiomyopathy by endomyocardial biopsy.

Ultrastructural evaluation of endomyocardial biopsy specimens is a sensitive and effective method with which to detect and quantitate cardiotoxicity produced by anthracylines. The procedure and grading system used at the M.D. Anderson Cancer Center are described, and some of the pitfalls that may be encountered by the electron microscopist are reviewed.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

A phase II evaluation of bexarotene (Targretin) capsules in patients with metastatic melanoma.

A phase II study was undertaken to determine the efficacy of Bexarotene in melanoma. Between November 1997 and April 1998, 19 patients were given Bexarotene in single daily oral doses of 450 mg/m2 in capsule form continuously. Nineteen patients, four with choroidal metastatic melanoma, were treated. No responses were seen. Five patients had stable disease, two of the four with choroidal melanoma, had tumor progression. Myelosuppression was mild. Grade 3 myalgia, asthenia, diarrhea, cold hands/feet, and mood changes were seen in one patient each. Changes in serum triglyceride and thyroxine levels were common. Bexarotene, as used in this study, is not effective against melanoma.

Adult↗
PubMedDate not supplied

Doxorubicin cardiotoxicity in children: reduced incidence of cardiac dysfunction associated with continuous-infusion schedules.

We retrospectively reviewed the medical records of 97 children (59 boys and 38 girls) with a median age of 13 +/- 4 years who had been treated with continuous infusion of doxorubicin at a dosage of 60 mg/m2 over 24 h (61 patients) or at a dosage of 75 mg/m2 over 72 h (36 patients). The drug was administered every 3 weeks. The cardiac status of patients was evaluated as a baseline and every 6 months during, and following therapy (median, 30.5 months). The evaluations included M-mode and two-dimensional echocardiography. Congestive heart failure developed in only one patient in this series, an 8-year-old girl who ultimately died of her cardiac complication. This incidence of doxorubicin-induced cardiotoxicity was compared with that seen in a control group of pediatric patients previously treated with doxorubicin at similar dosages but with a rapid infusion. The result compared favorably to the 13% incidence of cardiotoxicity (p = 0.03) and 7% mortality (p < 0.01) in the control group. No changes in the levels of tumor response were noted in children treated by continuous infusion when compared with historical controls. Continuous-infusion schedules of doxorubicin thus result in fewer incidences of cardiotoxicity in children and should be considered for wider application in pediatric cancer patients receiving doxorubicin.

Adolescent↗
PubMedDate not supplied

Cis-dichlorodiammineplatinum(II) in advanced soft tissue and bony sarcomas: a Southwest Oncology Group Study.

cis-Dichlorodiammineplatinum(II) (DDP), at a dose of 15 mg/m2/day x 5 consecutive days, was administered to 68 evaluable patients with metastatic soft tissue and bony sarcomas. All patients, except one, had received extensive prior chemotherapy and had had progressive disease at the start of the study. Responses observed included one complete response in a patient with mesothelioma and three partial responses in patients with soft tissue sarcomas (7%). No responses were seen in 18 patients with bony sarcomas. Significant leukopenia and thrombocytopenia were observed in less than 20% of evaluable courses, although two patients manifested life-threatening leukopenia (less than 1000 cells/microliter) and three had life-threatening thrombocytopenia (less than 24,000 cells/microliter). Nephrotoxicity was noted in less than 25% of evaluable courses. Nausea and/or vomiting was recorded in 55% of evaluable courses. DDP is considered to be marginally active in the secondary treatment of metastatic sarcomas at this dose and schedule. Further studies of DDP in mesothelioma are indicated.

Adolescent↗
PubMedDate not supplied

Phase II evaluation of AMSA in adult sarcomas.

AMSA an acridine derivative, was administered to 35 adults with previously treated advanced sarcomas. Patients with adequate bone marrow reserve received 120-150 mg/m2 of AMSA as a single dose repeated every 3 weeks. Patients with inadequate bone marrow reserve received 100-120 mg/m2 of AMSA. Among 31 evaluable patients, there was one partial response that lasted 6 months in a patient with intra-abdominal malignant fibrous histiocytoma with liver metastases. Thirteen patients had stable disease with a median time to disease progression of 5 months (range, 2-13), while 17 patients demonstrated progressive disease with a median time to disease progression of 2 months (range, 1-3). The median survival time for the 31 evaluable patients in this study was 5 months. The toxic effects were mild and included myelosuppression, nausea and vomiting, fever of unknown origin, and fatigue. At the dose and schedule used in this study, AMSA does not appear to have any significant activity in advanced sarcomas of adults.

Adolescent↗
PubMedDate not supplied

Distribution and inhibition of adenosine deaminase in tissues of man, rat, and mouse.

Adenosine deaminase activity, with arabinosyladenine (ara-A) used as the substrate, was measured in human leukemic cells and major tissues of man, rat, and mouse. The enzyme is stable in frozen tissues for at least 1 week, in frozen homogenate for several months, or after overnight dialysis at 4 degrees C in 0.25 M sucrose. The adenosine deaminase of chronic myelogenous leukemic (CML) cells has a Km of 0.6 mM and a Vmax of 183 mumols x 10(-2)/g of cells/minute. All species have highest activities in spleen and intestine. Kidney activity is highest in rat and lowest in man. The human brain has higher activity than the mouse or rat brain, and activity is higher in mouse liver than in human or rat liver. Activity in lung tissues is moderate and similar in all three species. The mean activity in CML cells is 195 mumols x 10(-2)/g of cells/minute, and the activity is higher in patients with CML in blast cell crisis. Acute myelogenous and lymphocytic leukemia cells also have very high activities. Drug concentrations required for inhibiting 50% of CML enzyme activity are 10 nM or erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), 0.6 nM of coformycin, and 0.3 nM of 2'-deoxycoformycin. Preincubation of the enzyme with coformycin, but not with EHNA, enhances the inhibition. In view of the high adenosine deaminase activities in tissues and the enhancement of the therapeutic effect of ara-A by inhibitors in mouse tumor systems, clinical trials of these combinations are warranted. They may be particularly beneficial to patients with CML in blast cell crisis.

Adenine↗