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Biomedical subjects

R S Benjamin

Publications and source records attributed to R S Benjamin.

At least 217 records · Page 12Linked to original sources
PubMed1979

Chemotherapy for sarcoma of the stomach.

The results of chemotherapy for patients with advanced leiomyosarcoma of gastric origin were analyzed. A total of 23 single-agent and multi-drug regimens were given to 17 patients. DTIC and adriamycin (ADR) were the most commonly used chemotherapeutic agents. ADR was used alone or in combination in 13 patients, resulting in partial responses in two patients and disease stabilization in seven. One of the partial responses was obtained with the ADR-DTIC combination and the other was obtained with the cyclophosphamide-vincristine-ADR-DTIC combination. The survival duration for the responders was significantly longer than that obtained for those patients who had disease stabilization or progression. The results of the study show that leiomyosarcoma of gastric origin is less sensitive to chemotherapeutic agents than leiomyosarcomas of other sites, as reported in the literature. New approaches based on the natural history of the disease and with potential to improve the results of treatment of gastrointestinal sarcomas are indicated.

Adult↗
PubMed1979

The effectiveness of rubidazone in hairy cell leukemia (leukemic reticuloendotheliosis).

Two patients with hairy cell leukemia treated with the anthracycline antibiotic rubidazone are presented. One achieved a complete remission and the other a good partial hematologic and bone marrow remission. Neither has relapsed (at 20 and 13 mo, respectively), and neither has been retreated. Intensive supportive measures were required during the prolonged myelosuppression that followed treatment. The relative youth of the patients (ages 24 and 39 yr) may have contributed to their ability to survive until normal marrow recovered. Chemotherapy should not be employed in the initial management of hairy cell leukemia. However, if life-threatening granulocytopenia and thrombocytopenia occur secondary to bone marrow replacement by leukemic cells, and improvement does not occur using alternative methods of therapy, consideration could be given to chemotherapy with rubidazone. Facilities for intensive supportive care should be available.

Adult↗
PubMed1979

Penetration of 3-deazauridine into human brain, intracerebral tumor, and cerebrospinal fluid.

The antitumor agent 3-deazauridine (DAU) was administered rapidly to four patients before surgical removal of intracerebral tumor. Tumor, adjacent brain tissue, and temporalis muscle were assayed for DAU by high-pressure liquid chromatography. DAU penetrated comparably into tumor, brain, and muscle; in one patient, tissue concentrations were higher than concurrent plasma concentrations. The active metabolite 3-deazauridine 5'-triphosphate was quantitated in one tumor sample and greatly exceeded its Ki for cytidine 5'-triphosphate synthetase. DAU was also present in autopsy brain specimens from two patients treated shortly antemortem. Cerebrospinal fluid concentrations were 22.1 and 59.0%, respectively, of concurrent plasma concentrations during continuous infusion of DAU in two patients. Cerebrospinal fluid concentration was 3.1 microgram/ml 2 hr after a 30-min infusion of 1.5 g of drug per sq m and fell to 1.9 microgram/ml at 16 hr. Thus, DAU is capable of penetrating into intracerebral tumor, brain, and cerebrospinal fluid and is worthy of investigation in the treatment of intracerebral and meningeal neoplasms.

3-Deazauridine↗
PubMed1979

Pharmacokinetics and disposition of 3-deazauridine in humans.

3-Deazauridine (3-DAU) pharmacology was studied in 20 patients who received the drug by rapid or continuous infusion. In 8 studies, the plasma clearance of 3-DAU after rapid administration was biphasic, with an average terminal t1/2 of 4.4 hr and an extrapolated volume of distribution of 0.57 liter/kg. After 5-day continuous infusion of 3-DAU, the plasma clearance was also biphasic, with an average terminal t1/2 of 21.3 hr and an extrapolated volume of distribution of 18.8 liter/kg. 2,4-Dihydroxypyridine, the aglycone of 3-DAU, was observed in plasma but not in urine of patients receiving the drug by rapid infusion. The urinary excretion of 3-DAU was low, only 7.8% 24 hr after rapid infusion and 7.2% up to 4 days after continuous infusion. Tissue distribution of 3-DAU was determined from autopsy samples of 2 patients. Not only were high levels of 3-DAU detected in the tissues studied, but 3-DAU triphosphate, the active metabolite of 3-DAU, was present in brain, lung, and liver.

3-Deazauridine↗
PubMed1978

Refractory acute leukaemia in adults treated with sequential colaspase and high-dose methotrexate.

Thirty-nine adults with acute leukaemia who had relapsed when receiving extensive chemotherapy were treated with a combination of methotrexate and colaspase (L-asparaginase) given sequentially. Patients initially received 50-80 mg/m(2) methotrexate, followed three hours later by intravenous colaspase, 40 000 IU/m(2). Seven days later intravenous methotrexate, 120 mg/m(2) was given. Each dose of methotrexate was followed 24 hours later by colaspase, and the two-day course of treatment was repeated every 7-14 days. The methotrexate dose was increased to tolerance by increments of 40 mg/m(2) with each course, while the colaspase dose remained constant unless abnormal liver function developed, when it was reduced by half.Overall, 18 out of 39 patients achieved complete remission (46%). Of these, 13 out of 21 (62%) had acute lymphoblastic leukaemia, three out of seven (43%) acute undifferentiated leukaemia, and two out of 11 (18%) acute myeloblastic leukaemia. The median duration of complete remission was 20 weeks and the median duration of survival in complete responders was 45 weeks. The median number of courses needed to achieve complete remission was three. The maximum tolerated dose of methotrexate was 400 mg/m(2) (median 200 mg/m(2)). Major side effects were due to colaspase. Methotrexate in doses of up to 400 mg/m(2) caused minimal myelosuppression and stomatitis, which suggested that colaspase given sequentially provides relative protection from methotrexate toxicity without the need for folinic acid (citrovorum factor) rescue.The combination of sequential colaspase and methotrexate is highly effective in reinducing remission in patients with acute lymphoblastic leukaemia or acute undifferentiated leukaemia. The regimen is easy to administer and relatively non-toxic, so it is suitable for use in outpatients, either alone or combined with other agents.

Acute Disease↗
PubMed1978

Neuroblastoma in the adult: effective combination chemotherapy.

Although neuroblastoma occurs most frequently in children, it also may occur in adults and has been considered of poor prognosis. Six adult patients (greater than 16 years of age) with widespread neuroblastoma diagnosed between 1974 and 1976 are described. Five were treated with a combination of cyclophosphamide, vincristine, adriamycin and dimethyl triazeno imidazole carboxamide (CYVADIC). The sixth received a similar regimen in which actinomycin D was substituted for dimethyl triazeno imidazole carboxamide (CYVADACT). There were two complete responses and three partial responses. The median duration of survival is in excess of 11 months. The results indicate that effective chemotherapy is now available for these patients and the achievement of remission and prolongation of survival are realistic goals in neuroblastoma.

Adolescent↗
PubMed1978

The value of adriamycin in the treatment of diffuse malignant pleural mesothelioma.

Thirty-six patients with diffuse malignant pleural mesothelioma were seen over a period of 15 years. The median age was 60 years (range, 21 to 75 years), and the male to female ratio was 2.3 to 1. The most common symptoms were chest pain and shortness of breath and all patients presented with pleural effusion on chest x-ray. The diagnosis was established by tissue biopsy in all cases. The median survival time for all patients was 12.5 months. Twenty-one patients were treated with an adriamycin-containing regimen and in this group, the median survival time from histological diagnosis was 14 months. In contrast, the median survival time for the 15 patients, who did not receive adriamycin, was 6 months (p = 0.009). The median survival time from the initiation of chemotherapy was 9 months for the adriamycin group and 2 months for patients treated with other type of chemotherapy (p = 0.001). Adriamycin appears to be of benefit in the treatment of diffuse malignant pleural mesothelioma.

Adult↗
PubMed1978

Adriamycin and other anthracycline antibiotics under study in the United States.

Adriamycin is now firmly established as a drug with a very broad spectrum of antitumor activity. It has had a major impact on the therapy of sarcomas. The dose response effect in this tumor is steep and combinations which compromise the dose of adriamycin too greatly are showing inferior results. In lung and breast cancer combinations with adriamycin have been extensively tried. The FAC Regimen in breast cancer has given excellent results at the M.D. Anderson Hospital. The inclusion of adriamycin in combinations has had an impact in the poor prognosis histologies of non-Hodgkin's lymphomas. The CHOP regimen is one of the best developed to date for diffuse histiocytic lymphomas. In the leukemias adriamycin is probably equivalent to daunorubicin which has been more extensively used in this country. A new analog called Rubidazone has shown good activity in AML with a smooth induction and its incorporation into combination with Ara-C, vincristine and prednisone in a regimen called ROAP is being investigated. Adriamycin in complex with DNA has been clinically evaluated, but at this time, no advantage for this approach can be demonstrated.

Antibiotics, Antineoplastic↗
PubMed1978

Clinical, toxicological, and pharmacological studies of combination chemotherapy of adenocarcinoma with adriamycin and Baker's antifolate.

Ten patients with disseminated adenocarcinoma were treated with combination chemotherapy employing Adriamycin and Baker's Antifolate (BAF). There were seven patients with lung adenocarcinoma, two of whom achieved partial remission while the remaining five had their disease stabilized. Drug toxicity to the bone marrow, gastrointestinal mucosa, and skin was dose-limiting and was greater than the known toxicities of the individual drugs. Pharmacological studies of both drugs were performed on five patients to determine whether abnormal pharmacokinetics could explain this collateral toxicity. Adriamycin plasma concentrations and disappearance seemed to be unaffected by BAF. However, BAF levels were prolonged, apparently due to an Adriamycin effect on the plasma elimination of BAF, resulting in a prolonged exposure of sensitive tissues and organs to BAF. Consequently, when BAF and Adriamycin are used in combination, appropriate dose and schedule changes must be made to avoid any potentially serious side effects.

Adenocarcinoma↗
PubMed1978

Kinetic response to cultured human lymphoid cells to rubidazone.

Analysis of rubidazone, the benzoylhydrazone derivative of daunorubicin, for its effects on cell cycle progression of a human lymphoid cell line showed a kinetic response pattern similar to that of adriamycin. Thus rubidazone induced a G2-block, the magnitude and duration of which were dependent on concentration and incubation time. However, in contrast to adriamycin, a marked phase-dependent sensitivity for the induction of G2-accumulation was observed; cells treated in early and mid-S-phase were most sensitive. This age-dependent kinetic response may account for the smaller G2-accumulation in asynchronous cultures and the closer correlation of the magnitude of this kinetic effect with concentration and duration of rubidazone treatment. Prolonged exposure to high concentrations of rubidazone also delayed the traverse through G1 and/or the G1-S transition, whereas the S-phase transit was not impaired. Interference with cell cycle progression through G1 into S-phase caused a stepwise accumulation of cells in G2-phase.

Cell Cycle↗
PubMed1978

Meningeal melanocytoma with invasion of the thoracic spinal cord. Case report.

A case is presented of meningeal melanocytoma that invaded the thoracic spinal cord of a 71-year-old woman. The light and electron microscopic features of the lesion indicate that it derives from melanocytes normally found in the leptomeninges. This tumor closely resembles the dermal cellular blue nevus and does not have the ultrastructure of a meningioma. "Melanotic meningioma" is consequently a misnomer and the name "meningeal melanocytoma" is more appropriate. These tumors may appear to be benign histologically, but they are locally aggressive. Total surgical excision offers the best chance for cure.

Aged↗
PubMed1978

Phase 1 clinical investigation of 4'-(9-acridinylamino)methanesulfon-m-anisidide (NSC 249992), a new acridine derivative.

The compound 4'-(9-acridinylamino)methanesulfon-m-anisidide is a new derivative that was evaluated in a Phase 1 clinical trial. The schedule of drug administration consisted of daily i.v. injection for 3 consecutive days, repeated at 3-week intervals. Twenty-six patients received a total of 63 courses of 4'-(9-acridinylamino)methanesulfon-m-anisidide in a dose range from 4 to 50 mg/sq m/day. Hematopoietic toxicity was dose limiting, but it was of short duration and rapidly reversible. Mild nausea and vomiting were observed in 16% of the courses, and a mild degree of phlebitis was observed in 10% of the courses. Responses were observed in two patients with adenocarcinoma of the lung and one each of melanoma and acute myeloblastic leukemia. Phase 2 studies of 4'-(9-acridinylamino)methanesulfon-m-anisidide are planned at a starting dose of 40 mg/sq m/day for 3 days in good-risk patients and at 25 to 30 mg/sq m/day for 3 days in poor-risk patients. Course of treatment would be repeated at 21-day intervals.

Acridines↗
PubMed1978

Acute myelomonocytic leukemia following a chemotherapeutic regimen for metastatic sarcoma.

Acute myelomonocytic leukemia developed in a patient 18 months after treatment with cyclophosphamide, vincristine, adriamycin, and DTIC, a chemotherapeutic regimen used for the treatment of metastatic sarcoma. The patient had had no prior history of radiation. More than 400 patients received this treatment and none of them developed leukemia. The occurrence of leukemia in this relatively short period of time may have been caused by the combined chemotherapeutic agents. However, confirmation of this will require long-term followup studies in cancer patients receiving chemotherapy to determine the true risk of second malignancies.

Drug Therapy, Combination↗