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Biomedical subjects

S D Reich

Publications and source records attributed to S D Reich.

16 recordsLinked to original sources
PubMed1988

Phase I/II study of recombinant interferon gamma in advanced renal cell carcinoma.

A phase I and II evaluation of 42 patients with advanced renal cell carcinoma treated with recombinant interferon gamma was done. Patients were treated with either a daily 2-hour infusion or 24-hour infusion for 7 days every 3 weeks for at least 2 cycles. Patients who demonstrated stable disease or improvement on therapy then were continued on a maintenance program of 5 days of recombinant interferon gamma administered every 3 to 4 weeks. The initial starting dose was 10 mcg. per m.2 per day with escalations to 30, 100, 300, 1,000 and 3,000 mcg. per m.2. Dose-limiting toxicity occurred at 1,000 to 3,000 mcg. per m.2, and included leukopenia, chills, fevers, rigors and hepatotoxicity as manifested by elevation in the transaminase and bilirubin levels. Tumor responses were seen initially at the 300 mcg. per m.2 dose level. Over-all, of 41 patients evaluable for therapeutic effectiveness 1 demonstrated a complete response 6 months in duration and 3 demonstrated partial responses 2, 9 and 13 months in duration. However, 6 patients demonstrated organ site responsiveness, including resolution of pulmonary lesions (2 complete and 1 partial responses), lymphadenopathy (1 complete and 1 partial responses), a pleural-based lesion in 1 patient with a partial response and complete resolution of hepatic metastases in 1 patient. We conclude that recombinant interferon gamma at a dose of 1,000 to 3,000 mcg. per m.2 for 7 days and repeated every 2 to 3 weeks had demonstrable anticancer activity in patients with metastatic renal carcinoma.

Adult↗
PubMed1988

A phase II study of the efficacy of recombinant interferon gamma in relapsing ovarian adenocarcinoma.

Fourteen patients with relapsing ovarian cancer were treated with a regimen of intravenous interferon gamma (IFN gamma). During an initial induction phase, patients received 2 mg/m2 IFN gamma intravenously over 2 h daily for 5 days, repeated every 2 weeks for six courses. Patients who responded were continued on a maintenance phase, receiving 3 mg/m2 intravenously over 2 h, twice weekly every 2 weeks for 2 to 6 months. All patients had received prior cisplatin containing chemotherapy regimens. Of the 14 patients entered, 7 completed the six courses of the induction treatment. Four patients were clinical responders and continued on maintenance therapy. The most commonly reported toxicities included malaise, fever, and deteriorating performance status. There appears to be some clinically apparent antitumor activity demonstrated by this dosing schedule of interferon gamma in ovarian cancers.

Adenocarcinoma↗
PubMed1987

A randomized phase I/II study of continuous versus intermittent intravenous interferon gamma in patients with metastatic melanoma.

Thirty patients with documented metastatic melanoma were randomly assigned to receive recombinant DNA-produced gamma-interferon (specific activity approximately, 20 MU/mg) intravenously (IV) over either two or 24 hours at dosages of 3, 30, 300, 1,000, or 3,000 micrograms/m2. Objective toxicity resembled that of alpha-interferon and included fever, chills, myalgias, headache, and fatigue. Neutropenia, elevations in liver enzymes, tachyarrhythmias, and CNS changes also were noted. Dose-limiting toxicity included neutropenia, liver enzyme abnormality, constitutional symptoms, and a change in mental status. The incidence of toxicity was qualitatively similar in both two- and 24-hour treatment arms, but was quantitatively more severe in the 24-hour continuous infusion arm. Maximum tolerated dose was 1,000 micrograms/m2 in both schedules. Pharmacokinetic studies showed a half-life of six to nine hours. One patient had a complete response after two cycles of therapy and an additional patient entered partial remission after three cycles. Recombinant gamma-interferon (rIRN-gamma) is tolerated at dosages of 1,000 micrograms/m2 administered daily either by two or 24 hour infusion for 14 days in patients with metastatic melanoma. The responses documented in this early trial warrant further evaluation for the treatment of metastatic melanoma.

Adult↗
PubMed1986

Recombinant gamma interferon in advanced breast cancer: a phase II trial.

Fifteen patients with advanced carcinoma of the breast who had failed prior chemotherapy, were treated with recombinant gamma interferon at a dose of 2mg/m2 (1mg = 2.4 X 10(7) international units) intravenously for five consecutive days every other week. The median patient age was 51 and all patients had a performance status of 0-2 (Karnofsky greater than or equal to 50). Thirteen patients had two or three sites of metastatic disease and seven were estrogen receptor positive. No complete or partial responses were noted. Although some patients had brief periods of stable disease, almost all patients progressed after one or two courses. Only one patient was able to receive six courses of induction therapy and a brief course of maintenance. Flu-like symptoms and nausea were seen in all patients; vomiting and anorexia were frequent. Hepatic toxicity manifested by enzyme elevation was common and was most severe in patients with liver metastases. In this study a highly purified biologically active gamma interferon was not associated with anti-tumor activity in previously treated women with metastatic breast cancer.

Adult↗
PubMed1986

Hyponatremia and other toxic effects during a phase I trial of recombinant human gamma interferon and vinblastine.

Recombinant human gamma interferon (Biogen) and vinblastine were administered in a phase I study. Side effects included fever and chills, nausea and vomiting, acute symptomatic hyponatremia, reversible myelosuppression, hepatitis, transient hypotension, congestive heart failure, renal insufficiency, and nonselective proteinuria. In most patients, additional host factors contributed to these toxic effects. Side effects occurred despite dose reduction; therefore, protocol accrual was prematurely closed. No correlation between serum concentrations and toxicity was noted. Median serum vinblastine concentration was 1.04 ng/ml; median serum interferon concentration was 17.3 IU/ml.

Aged↗
PubMed1979

Mathematical modeling -- guide to high-dose methotrexate infusion therapy.

A mathematical model that describes methotrexate pharmacokinetics has been refined for use as a guide to dose escalation during high-dose methotrexate infusion therapy. Parameters for the model are adjusted for a patients by the SAAM computer program of Berman and Weiss, on the basis of plasma concentrations obtained during the initial course of therapy. Various dose escalations can be simulated by the computer and a print-out of predicted plasma concentrations obtains. The model has been used successfully to predict plasma concentrations after high-dose infusions in patients, including those with abnormal creatinine clearances. The program is designed to allow comparisons among infusions of any duration. This can be helpful when a change from a 24-hour infusion to a 6-hour infusion is contemplated for a patient. Deviations of observed values from those predicted are used to warn of the possibility of delayed toxicity secondary to methotrexate and alert the physician that increased amounts of rescue agent may be required.

Carcinoma, Squamous Cell↗
PubMed1979

Mathematical model for adriamycin (doxorubicin) pharmacokinetics.

Adriamycin (doxorubicin), an active antineoplastic drug, is rapidly distributed across cell membranes and is concentrated within cells. Binding to protein and to tissue readily occurs. The drug is metabolized to both fluorescent and nonfluorescent compounds, the liver being the main organ of biotransformation and elimination. A multicompartment, open model that accounts for these processes has been derived. The model assumes an initial volume of distribution of 60% of body weight and includes two peripheral adriamycin compartments and a subsystem for adriamycinol, a major metabolite. Plasma and urine concentrations of adriamycin and adriamycinol were determined for four patients treated with adriamycin (60 mg/m2), and these concentrations were used to calculate rate constants for the model. Concentrations were measured by fluorescence assay after thin-layer chromatographic separation of parent compound and metabolites. Differential equations were solved by the SAAM computer program. Evaluation of adriamcinol pharmacokinetics suggests that the previously reported high concentrations of adriamycinol immediately after IV infusion of adriamycin are an artifact of the fluorescence method and that observed plasma concentrations of adriamycinol are the sum of adriamycinol concentrations and approximately 10% of the adriamycin concentrations. Corrected peak plasma concentrations of adriamycinol occur 2--12 h after infusion of adriamycin.

Doxorubicin↗
PubMed1979

Bleomycin.

Bleomycin was approved by the Food and Drug Administration in 1975 for therapy against squamous cell carcinomas, testicular cancers, and malignant lymphomas. An extensive bibliography on this drug indicates that there is little evidence of activity against other malignancies. Although initially used exclusively as a single agent, bleomycin has been considered recently for use in combination chemotherapy. Because of associated toxicity involving the lung and mucous membranes, bleomycin should be used cautiously by physicians, particularly in noninvestigational settings.

Bleomycin↗
PubMed1978

Hemoperfusion for methotrexate removal.

Removal of methotrexate by Amberlite XAD-4 hemoperfusion was determined in a patient with metastatic breast carcinoma. During 4 hr of hemoperfusion the plasma concentration of methotrexate fell from 5.5 x 10(-7) M TO 3.1 x 10(-7) M. After hemoperfusion methotrexate concentration increased as a consequence of multicompartmental pharmacokinetics to 5.5 x 10(-7) M and then slowly declined. Plasma methotrexate clearance decreased from 79 ml/min 30 min into hemoperfusion to 28 ml/min at the conclusion. In vitro clearance of methotrexate by 17 artificial kidneys, Amberlite XAD-4, and uncoated charcoal was determined. Uncoated charcoal had the greatest clearance of methotrexate of all the devices tested. We conclude that: (1) Amberlite XAD-4 transiently reduces plasma methotrexate concentration; (2) in vitro, charcoal hemoperfusion is more effective than XAD-4 in removing methotrexate; (3) as a consequence of the multicompartmental pharmacokinetics of methotrexate a postperfusion rebound in plasma methotrexate concentration is to be expected.

Charcoal↗
PubMed1976

Von Recklinghausen neurofibromatosis and acute leukemia.

The leukemias are neoplastic processes that have been associated with a variety of genetic disorders. A case of an adolescent with both acute myelomonocytic leukemia and von Recklinghausen disease is presented, and the literature reviewed to show that these two diseases are associated. Although the number of cases in the literature suggests that in children with von Recklinghausen disease there is a greater risk of leukemia developing, prospective studies are needed to prove this point.

Adolescent↗
PubMed1976

Alterations in adriamycin efficacy by phenobarbital.

Adriamycin dosage should be reduced in patients with impaired liver function, since adriamycin disposition is influenced by liver metabolism and biliary excretion. It follows that drugs that increase the metabolism or excretory capacity of the liver may decrease adriamycin concentrations to suboptimal values. Adriamycin metabolism was therefore studied in mice pretreated with phenobarbital (75 mg/kg i.v.) by injection. After an i.v. dose of adriamycin (30 mg/kg i.v.), plasma fluorescence due to drug and metabolites was less and disappeared at a greater rate in phenobarbital-pretreated mice than control animals. When extracted with chloroform: isoprophyl alcohol (1:1), the livers from the phenobarbital-pretreated group yielded a greater concentration of glycones. Experiments with liver microsomes confirmed that aglycone production occurred at a more rapid initial rate in phenobarbital-induced livers. No increase in aldoketo reductase (daunorubicin reductase) activity was noted. Phenobarbital-pretreated mice, inoculated i.p. with 1 million L1210 cells and then treated with adriamycin (6 mg/kg i.v.), had significantly lower survival than did controls (p less than 0.01). These findings show that phenobarbital affects the disposition of adriamycin by microsomal enzyme induction and suggest that drugs that induce microsomal enzymes should not be used concurrently with adriamycin if optimal drug efficacy is desired.

Alcohol Oxidoreductases↗