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Biomedical subjects

R S Benjamin

Publications and source records attributed to R S Benjamin.

At least 163 records · Page 9Linked to original sources
PubMed1982

Adriamycin therapy by continuous intravenous infusion in patients with metastatic breast cancer.

Patients with metastatic breast cancer previously treated with non-Adriamycin containing chemotherapy were treated with Adriamycin at a dose of 60 mg/m2 administered as a continuous infusion through a central venous catheter. The duration of Adriamycin infusion was escalated by 100% increments from 24-96 hours, but the majority of patients were maintained on 96-hour infusions. Thirteen of 27 patients achieved objective response (1 CR, 12 PR), six improved, and eight failed to respond to Adriamycin. Administration of Adriamycin by infusion led to a decrease in the severity of nausea and vomiting, but had no effect on myelosuppression and alopecia secondary to Adriamycin. The cardiac toxicity of Adriamycin was reduced in patients who received maintenance therapy with 96-hour infusions of Adriamycin.

Adult↗
PubMed1982

Human tissue distribution of platinum after cis-diamminedichloroplatinum.

Using X-ray fluorescence spectrometry, platinum concentrations were determined in autopsy tissue samples from 12 patients who had received cis-diamminedichloroplatinum (DDP) 20-120 mg/m2 up to 6 months antemortem. Tissue platinum concentrations were highest in liver (0.5-3.7 micrograms/g wet weight), prostate (1.6-3.6 micrograms/g), and kidney (0.4-2.9 micrograms/g), somewhat lower in bladder, muscle, testicle, pancreas, and spleen, and lowest in bowel, adrenal, heart, lung, cerebrum, and cerebellum, Platinum concentrations in tumors were generally somewhat lower than the concentration in the organ in which the tumor was located, with the exception of intracerebral tumors. Different metastatic sites in the same patient had substantially different platinum concentrations and hepatic metastases had the highest concentrations. Intra-arterial administration of drug may augment tissue concentrations of platinum. In a patient undergoing therapeutic abortion 4 days after treatment, the platinum concentration was 0.5 micrograms/g in the placenta and 0.3 micrograms/g in the fetus. The data suggest that for in vitro sensitivity testing, DDP concentrations of less than or equal to 7 micrograms/ml should be used.

Autopsy↗
PubMed1982

Clinical pharmacology of bruceantin by radioimmunoassay.

During the phase I clinical trial of a new antitumor agent, bruceantin, the pharmacology was studied in 18 cancer patients. The drug was infused intravenously (IV) for 3 h at doses ranging from 1 to 3.6 mg/m2 per day for 5 days. The plasma drug disappearance curves were biphasic, with a fast initial half-life of less than 15 min. The second half-life (t1/2 beta) varied from 0.7 to 38 h among different patients and was not dose-related. The difference between the t1/2 beta on day 1 and that on day 5 was not significant. In patients with normal liver function, the mean plasma concentration at the end of infusion was 22 ng/ml, and the value of the area under the concentration X time curve (AUC) was 111 (ng/ml)h. In contrast, in patients with abnormal liver function the corresponding values were 115 ng/ml and 830 (ng/ml)h, respectively. In addition, these patients had a slower elimination half-life of 10.9 h and a decreased total clearance of 157 ml/min/m2, as compared with 2.6 h and 671 ml/min/m2, respectively, for the normal group. All these differences were statistically significant. Patients with abnormal liver function developed more severe toxicity, including fever, severe nausea, vomiting, and hypotension. Two patients with severe hepatic dysfunction received a reduced dose and developed no toxicity. These results demonstrated the importance of the effects of liver dysfunction on drug disposition and showed that the dosage should be reduced in patients with hepatic dysfunction.

Antineoplastic Agents, Phytogenic↗
PubMed1982

Bleomycin clinical pharmacology by radioimmunoassay.

Bleomycin pharmacokinetics were studied by radioimmunoassay in 11 patients who received 7-30 U intravenously (IV) and eight patients who received 4-30 U subcutaneously (SC). For patients who received IV bleomycin plasma disappearance was biphasic, with a mean initial half-life of 0.26 h and a terminal half-life of 2.3 h. Mean plasma drug clearance was 67.8 ml/min/m2 and the volume of distribution was 13.2 l/m2. Urinary excretion accounted for 63.9% of the drug in 24 h. After SC administration peak plasma levels occurred in 1.1 h, with a mean elimination half-life of 4.3 h. Mean plasma drug clearance was 60.5 ml/min/m2 and the volume of distribution was 19.2 l/m2. Bleomycin plasma clearance correlated well with serum creatinine (r2 = 0.72). Bleomycin has a rapid plasma elimination and urinary excretion. Bleomycin bioavailability after SC administration appears comparable to that seen after IV administration as determined by the areas under the plasma disappearance curves. Prolonged plasma levels are seen after SC injection, suggesting this route of administration can produce plasma concentrations comparable to those attained with continuous IV infusions.

Adolescent↗
PubMed1982

Intraarterial management of giant-cell tumors of the spine in children.

Transcatheter arterial management of giant cell tumors of the spine was performed in two female patients aged 12 and 15 who had failed to respond to conventional therapy. Response was determined clinically by alleviation of pain and radiographically by regression and/or calcification of the tumor. Minor side effects included transient nausea, elevated body temperature, and pain.

Adolescent↗
PubMed1982

Clinical kinetics of 1, 4-dihydroxy-5,8-bis [(2-[(2-hydroxyethyl) amino] ethyl] amino ]-9, 10-anthracenedione.

The clinical kinetics of 1, 4-dihydroxy-5,8-bis[[ 2-[(2-hydroxyethyl) amino] ethyl] amino]-9,10-anthracenedione dihydrochloride (DHAQ) are reported. DHAQ, 1 to 3 mg/m2, was administered as an intravenous bolus to six patients with metastatic cancer. Plasma clearance of the drug followed a biphasic pattern with a harmonic mean initial half-life (t 1/2) of 13.7 min and a terminal t 1/2 of 37.4 hr. Recovery of unchanged drug in the urine was 6.8% at 24 hr and 7.3% at 72 hr, while the corresponding recovery of total radioactivity was 9.4% and 11.3%. Apparent volume of distribution of DHAQ was about 13.8 +/- 2.9 l/kg. Total clearance was 238.7 ml/kg/hr, twice the creatinine clearance.

Adult↗
PubMed1982

Clinical and pharmacologic investigation of the effects of alpha-tocopherol on adriamycin cardiotoxicity.

Our data indicate that alpha-tocopherol used in an oral dose of 2 g/m2 daily results in a six- to eightfold increase of the vitamin E levels in serum. The occurrence of congestive heart failure in three patients and the observation of significant pathologic changes in endomyocardial biopsies in approximately half of the patients treated with a median cumulative adriamycin dose level of 550 mg/m2 indicate that alpha-tocopherol does not offer substantial protection against adriamycin-induced cardiac toxicity. The antitumor activity of the drug, however, is not compromised by the concomitant administration of the vitamin.

Adult↗
PubMed1982

Intra-arterial chemotherapy of malignant fibrous histiocytoma of the pelvis.

In 3 cases of malignant fibrous histiocytoma of the bony pelvis, intra-arterial chemotherapy was followed by surgical resection when possible in an attempt to control local disease without unacceptable deformity and treat undetected systemic metastases. Cis-diamminedichloroplatinum (CDDP) and a combination of intra-arterial doxorubicin, 5-(dimethyltriazeno)imidazole-4-carboxamide, and intravenous cyclophosphamide (CYADIC) were used. In 2 patients who underwent surgical resection, no viable tumor cells were found. The third patient did not respond to these or other forms of treatment. The patients treated with resection have shown no evidence of local recurrence at 24 and 9 months, respectively.

Adult↗
PubMed1982

Reduction of doxorubicin cardiotoxicity by prolonged continuous intravenous infusion.

Doxorubicin (Adriamycin) was administered by continuous infusion to reduce peak plasma levels and thus lessen cardiac toxicity. Cardiotoxicity was monitored by noninvasive methods, and endomyocardial biopsy specimens were studied by electronmicroscopy. Cardiotoxicity was compared in 21 patients receiving doxorubicin intravenously over 48 or 96 hours and in 30 control patients treated by standard intravenous injection. Both groups were studied prospectively and were well matched by risk factors for doxorubicin cardiotoxicity. The median cumulative dose for those receiving continuous infusion was 600 mg/m2 body surface area (range, 360 to 1500 mg/m2) compared with 465 mg/m2 (range 290 to 680 mg/m2) in the control group (p = 0.002). Fourteen of the 30 patients in the control group showed severe morphologic changes in the biopsy specimens, precluding further doxorubicin administration, as compared with two of 21 patients receiving the drug by continuous infusion (p less than 0.02). The mean pathologic score for the infusion group, 0.9, was lower than the mean for the control group, 1.6 (p = 0.004). Antitumor activity was not compromised. Decreasing peak plasma levels of doxorubicin by continuous infusion reduces cardiotoxicity.

Adult↗
PubMed1982

Modulation of 9-beta-D-arabinofuranosyladenine 5'-triphosphate and deoxyadenosine triphosphate in leukemic cells by 2'-deoxycoformycin during therapy with 9-beta-D-arabinofuranosyladenine.

The effect of the adenosine deaminase inhibitor, 2'-deoxycoformycin, on cellular nucleotides during therapy with continuous infusion of 9-beta-D-arabinofuranosyladenine (ara-A) has been investigated. In three courses of treatment using increasing doses, the active 5'-triphosphate of ara-A, 9-beta-D-arabinofuranosyladenine 5'-triphosphate (ara-ATP) accumulated in leukemic cells and erythrocytes from a patient treated for acute lymphocytic leukemia in proportion to the dose of ara-A. The cellular ara-ATP concentration increased more than 5-fold after the injection of a single, nontoxic, but pharmacologically active dose of 2'-deoxycoformycin 24 hr after initiation of ara-A infusion. However, this response was associated with a concomitant increase in the cellular deoxyadenosine triphosphate concentrations to levels equal to or greater than those of ara-ATP throughout the three treatment courses studied. Consistent with previous results using cell-free systems, it was demonstrated that a competitive relationship exists between deoxyadenosine triphosphate and ara-ATP for the inhibition of DNA synthesis in cultured human lymphoblastoid cells and that the ratio of the cellular concentrations of these nucleotides could predict the extent of inhibition of DNA synthesis. Application of this rationale to the nucleotides in the leukemic cells of the patient suggested that administration of 2'-deoxycoformycin may create a cellular biochemical milieu that could be antagonistic to the inhibition of DNA synthesis by ara-ATP.

Adult↗
PubMed1982

The natural history of metastatic synovial sarcoma: experience of the Southwest Oncology group.

Of 35 treated cases of metastatic synovial sarcoma, there was a slight male predominance (60%). The median age was 33 years, with 88% of the patients being white. The lower extremity was the most common primary site, occurring in 66% of the cases. The most common metastatic involvement was pulmonary (33 patients), with only three patients having lymph node involvement. The low incidence of lymph node involvement and the poor prognosis when positive lymph nodes are found suggest that prophylactic lymph node resection is unwarranted. The median time from evidence of metastases to death was ten months. The complete and partial response rate to chemotherapy in this series was 50%; however, duration of the response was rather short with recurrence of metastatic disease a median of seven months after response was first noted. The size of the primary lesion was greater than 5 cm in all but one of the cases. The local recurrence rate was 70% in those cases undergoing local resection and 30% in those cases in which local resection plus irradiation to the primary lesion was undertaken. No case in which radical resection of the primary tumor was undertaken had a local recurrence.

Adolescent↗
PubMed1982

Doxorubicin-DNA complex: a phase I clinical trial.

Thirty-five patients with advanced malignancies were treated with doxorubicin-DNA complex in a phase I clinical trial. The patients ranged in age from 30 to 77 years (median, 51) and received doxorubicin-DNA in doses that ranged from 20 to 135 mg/m2. Of the doses administered, 73% were 60-90 mg/m2 (median, 60). Nonhematologic toxic effects included nausea and vomiting in 32% of the patients, fever and chills in 24% mucositis in 18%, and decreases in ECG QRS voltage of greater than 30% in 18%. Fever of unknown origin was seen in 26% of the patients, with documented infection in 9%; 6% had drug-related deaths. All patients experienced alopecia. Hematologic toxic effects (median day, Day 14) included median granulocyte count nadirs of 0.8 X 10(3)/microliter at a 60-mg/m2 dose and 0.3 X 10(3)/microliter at 75 mg/m2. Thrombocytopenia was less severe, with median nadir counts of 131,000 cells/microliter at a 60-mg/m2 dose on median day. Day 13. Treatment courses could be repeated every 3 weeks. Clinical responses (complete plus partial) were seen in 12% of the patients, with an additional 48% showing stable disease. No patients entered in the study were known to be doxorubicin-resistant. Based on these data, we recommend a starting dose of 60 mg/m2 in patients with adequate bone marrow reserve and 50 mg/m2 in those with compromised bone marrows. Doxorubicin-DNA exhibits major clinical toxic effects on the gastrointestinal and hematopoietic systems, with dose-limiting granulocytopenia.

Adult↗
PubMed1982

A phase I study of intracarotid artery infusion of cis-Diamminedichloroplatinum(II) in patients with recurrent malignant intracerebral tumors.

A phase I study of intracarotid cis-diamminedichloroplatinum was performed in 11 patients with intracerebral tumors (five glioblastoma, four melanoma, one meningeal sarcoma, and one lung carcinoma) progressing after radiation +/- chemotherapy. The internal carotid artery was temporarily cannulated by a percutaneous transfemoral approach. All patients received i.v. heparin, mannitol, and fluids; seven received dexamethasone, 50 mg i.v., twice the day before and the day of treatment. Intracarotid cis-diamminedichloroplatinum, 60 to 100 mg/sq m in 175 to 250 ml 0.45% NaCl solution with 1000 units heparin, was infused over 1 hr. Six patients received two or more courses (maximum of 6) at 2- to 8-week intervals. Gastrointestinal toxicity was mild to moderate. Ototoxicity was minor. Central nervous system (CNS) toxicity was focal, severe, permanent, and possibly due to embolus in one patient at 75 mg/sq m; focal and reversible in one patient at 100 mg/sq m; and generalized but reversible in one patient at 75 mg/sq m. Possible CNS toxicity was noted in two additional patients. Two patients with CNS toxicity developed permanent ipsilateral retinal toxicity, and one patients without CNS toxicity developed bilateral decreased visual and auditory acuity 2 weeks after his sixth treatment. Renal and hematological toxicity and orbital pain were mild. Response status included: early death, one; probable responses, six (2+ 4+, 6, 6+, 8, and 8+ months); stabilization, two (3+ and 4 months); and failure, two. We recommend cis-diamminedichloroplatinum (60 mg/sq m) every 2 to 4 weeks for Phase II studies. Severe CNS and retinal toxicity are possible.

Adult↗
PubMed1981

A phase II evaluation of methyl CCNU and actinomycin D in the treatment of advanced sarcomas in adults.

Twenty-nine patients with metastatic sarcoma were treated with a combination of methyl CCNU and actinomycin D. Patients with adequate bone marrow reserve received methyl CCNU 100 mg/m2 orally on day 1 and actinomycin D 0.3 mg/m2/day intravenously for five days. Both drugs were repeated every four weeks. Patients with inadequate bone marrow reserve received methyl CCNU 75 mg/m2 and actinomycin D 0.2 mg/m2/day for five days. All patients had received prior chemotherapy and had progressive disease at the start of the study. There was one complete response in a patient with peritoneal mesothelioma which lasted 18 months and the patient is still alive at 38+ months. Ten patients had stable disease including three patients who had responses between 25% to 50%. No responses were seen in 18 patients. The median time to progression for patients with stable disease was five months and for those with progressive disease was two months (P = 0.001). The median survival for patients with stable disease was 20 months compared with three months for patients with progressive disease (P = 0.001). The combination was generally very well tolerated and myelosuppression was insignificant. However, with the dosages and schedule used in this study, the combination of methyl CCNU and actinomycin D does not appear to have significant activity in advanced soft tissue sarcomas. Further studies with this combination are indicated in patients with mesothelioma.

Adult↗
PubMed1981

Protected environment - prophylactic antibiotic program for malignant sarcomas: randomized trial during remission induction chemotherapy.

Fifty-one valuable patients with malignant sarcomas were randomly allocated to receive three courses of remission induction chemotherapy with cyclophosphamide, vincristine, Adriamycin, and dimethyl triazeno imidazole carboxamide (CYVADIC) on the protected environment-prophylactic antibiotic for the control group (P = 0.22). The response rates (complete plus partial) were 71% and 67%, respectively. The durations of response were similar for both groups of patients, but the PEPA patients survived substantially longer (median, 84 weeks vs. 58 weeks). The frequency of infection was significantly lower among the PEPA patients, and the doses of CYVADIC could be escalated more often among these patients. Dosage escalation was associated with a higher complete remission rate and lower fatality rate.

Adolescent↗