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Multidrug resistance (MDR), especially that associated with overexpression of MDR1 and its product, P-glycoprotein (Pgp), is thought to play a role in the outcome of therapy for some human tumors; however, a consensus conclusion has been difficult to reach, owing to the variable results published by different laboratories. Many factors appear to influence(More)
PURPOSE To determine the effects of high-dose cyclosporine (CsA) infusion on the pharmacokinetics of etoposide in patients with cancer. PATIENTS AND METHODS Sixteen patients were administered 20 paired courses of etoposide and CsA/etoposide. Etoposide was administered daily for three days, alone or with CsA, which was delivered by a loading dose and 3-day(More)
PURPOSE To study the effects of cyclosporine (CsA), a modulator of multidrug resistance (MDR), on the pharmacokinetics and toxicities of doxorubicin. PATIENTS AND METHODS Nineteen patients with incurable malignancies entered this phase I trial. Initially patients received doxorubicin alone (60 or 75 mg/m2) as a 48-hour continuous intravenous (i.v.)(More)
We conducted a trial of a murine monoclonal antimelanoma antibody-ricin A chain immunotoxin (XOMAZYME-MEL) in 22 patients with metastatic malignant melanoma. The dose of immunotoxin administered ranged from 0.01 mg/kg daily for 5 days to 1 mg/kg daily for 4 days (total dose: 3.2 to 300 mg). Side effects observed in most patients were a transient fall in(More)
A growing body of evidence indicates that expression of the mdr1 gene, which encodes the multidrug transporter, P-glycoprotein, contributes to chemotherapeutic resistance of human cancers. Expression of this protein in normal tissues such as the biliary tract, intestines, and renal tubules suggests a role in the excretion of toxins. Modulation of(More)
PURPOSE To determine the maximum-tolerated dose (MTD) of cyclosporine (CsA) infusion administered with etoposide for 3 days in patients with cancer. PATIENTS AND METHODS Of the 72 registered patients, 26 were treated initially with CsA and etoposide. Forty-six received etoposide alone until disease progression, and 31 of these proceeded to CsA and(More)
PURPOSE To determine the remission rate and toxicity of mitoxantrone, etoposide, and cyclosporine (MEC) therapy, multidrug resistance-1 (MDR1) status, and steady-state cyclosporine (CSA) levels in children with relapsed and/or refractory acute myeloid leukemia. PATIENTS AND METHODS MEC therapy consisted of mitoxantrone 6 mg/m(2)/d for 5 days, etoposide 60(More)
BACKGROUND The hypervascular nature of hepatocellular carcinoma (HCC) is well characterized. Recent data have suggested that thalidomide possesses antiangiogenic and immunomodulatory activity. Therefore, the authors initiated a study to assess the efficacy and toxicity of thalidomide in patients with advanced HCC as primary and secondary endpoints,(More)
The multidrug resistance gene mdr1, encoding P-glycoprotein (P-gp), can be expressed at high levels in tumour cells derived from normal tissues with constitutive high expression of this gene. In myelogenous leukaemia, the incidence of increased expression of mdr1 gene contrasts with the low expression of this gene in normal bone marrow (b.m.). To detect(More)
Although hypophosphatemia has been implicated as a cause of respiratory failure, its impact on respiratory muscle function in patients hospitalized for other reasons remains to be determined. Maximal inspiratory pressures (MIP) and maximal expiratory pressures (MEP) were measured at the bedside in 23 hospitalized patients with serum phosphate levels less(More)