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Biomedical subjects

E C Cadman

Publications and source records attributed to E C Cadman.

At least 37 records · Page 2Linked to original sources
PubMed1986

Pretreatment hematocrit as an independent prognostic variable in Hodgkin's disease.

Pretreatment hematocrit in 117 advanced-stage Hodgkin's disease patients treated with a combined modality therapy program was evaluated as an independent prognostic variable with regard to survival and relapse-free survival. Age greater than 40 years, and multiple extranodal sites of involvement were found to be statistically significant independent negative prognostic factors with regard to survival. Pretreatment hematocrit, however, was not an independent negative prognostic variable.

Adult↗
PubMed1985

Retroperitoneal mass presentations of B-immunoblastic sarcoma.

A clinicopathologic analysis of nine patients with B-immunoblastic sarcoma (B-IBS) presenting as a bulky lymph node-based retroperitoneal mass is reported. The histologic and immunologic findings, similar to those reported in B-IBS presenting in various other nodal and extranodal sites, support the recognition of this aggressive large cell non-Hodgkin's lymphoma (NHL) as a distinct pathologic entity. The patients, with a mean age of 60.5 years, presented for evaluation of abdominal pain and a palpable abdominal mass. Four patients were Stage II or IIE, one Stage III, and four Stage IV; eight of nine had B symptoms. Chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone, bleomycin [CHOP-B] or cyclophosphamide, doxorubicin, vincristine, methotrexate with leucovorin rescue, cytarabine [ACOMLA]) yielded significant palliation in five patients (mean survival, 12.3 months); three untreated patients and one receiving radiation treatment (XRT) died within 1 month from diagnosis. There was a striking predilection for pleuropulmonary involvement in disseminating disease. The initial blood lymphocyte count correlated significantly with survival (correlation coefficient, 0.84). The one durable complete remission (CR) was obtained in a patient who received substantial surgical debulking before chemotherapy.

Adult↗
PubMed1985

Inhibition of growth of leukemic cells by inhibitors of calmodulin: phenothiazines and melittin.

Calmodulin, a ubiquitous calcium-binding protein, has recently been shown to play an important role in cellular proliferation. The calmodulin inhibitors melittin, trifluoperazine, and chlorpromazine inhibited the growth and clonogenicity of human and murine leukemic cells, and their potency reflected their activity as inhibitors of calmodulin. Melittin, which is a far more potent inhibitor of calmodulin activity, was also a more potent inhibitor of cell growth and clonogenicity. The less active phenothiazine metabolite, chlorpromazine sulfoxide, had much less potent cytotoxic activity.

Animals↗
PubMed1985

Altered plasma kinetics of 5-FU at high dosage in rat and man.

To provide a model for pharmacokinetic studies in patients administered high iv doses of 5-FU after allopurinol or other modifiers of toxicity, rats were given radioactive 5-FU as an iv bolus. At a dose of 50 mg/m2 only 16% of circulating radioactivity was identified as 5-FU after 30 minutes, whereas greater than 90% of radioactivity was 5-FU when rats were given a 1800-mg/m2 dose. This 36-fold increase in 5-FU dose was associated with a greater than 150-fold increase in the 30-minute plasma concentration of 5-FU (0.02-3.3 mM). In patients, it was possible to increase the maximum tolerated dose of 5-FU given as a weekly rapid iv bolus from 800 to 1700 mg/m2 when a 3-day course of allopurinol (900 mg/day orally) preceded 5-FU administration. A dose-dependent increase in the apparent half-life of 5-FU in the plasma was observed and plasma concentrations at 30 minutes were as high as 500 microM after a 1600-mg/m2 dose of the drug.

Animals↗
PubMed1985

Ultrafiltrate and total platinum in plasma and cerebrospinal fluid in a patient with neuroblastoma.

Ultrafiltrate and total plasma and cerebrospinal fluid (CSF) platinum concentrations were examined in a patient with neuroblastoma following a 2-hour infusion of 120 mg/m2 of cisplatin. Total plasma platinum was 93.4% bound, while the ultrafiltrate of plasma accounted for the remaining 6.6%. The CSF ultrafiltrate resulted in equivalent concentrations of platinum to total CSF platinum. CSF concentrations were 2.9% of the total plasma platinum and 43.5% of the ultrafiltrate plasma platinum 2 hours after the end of the infusion.

Brain Neoplasms↗
PubMed1984

Sequential methotrexate and 5-FU in CMFP (cyclophosphamide, methotrexate, 5-FU, and prednisone) therapy for breast cancer.

Forty-one women with advanced breast cancer were treated with cyclophosphamide, methotrexate, 5-FU, and prednisone. Methotrexate (200 mg/m2) was given iv 1 hour before administering 5-FU (600 mg/m2). Leucovorin (10 mg orally every 6 hours for six doses) was begun 24 hours after the methotrexate. The response rate was 43%, with 19% of patients having a clinically complete remission. This overall objective response rate is lower than that achieved when this drug combination is given at standard doses of methotrexate and with no interval before 5-FU. Toxicity was primarily related to bone marrow suppression; eight women had wbc counts that fell to less than 1500/mm3.

Adult↗
PubMed1984

The design of rational combination chemotherapy for cancer.

These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from transcriptions, they are prepared by Drs Homer A. Boushey, Associate Professor of Medicine, and David G. Warnock, Associate Professor of Medicine, under the direction of Dr Lloyd H. Smith, Jr, Professor of Medicine and Chairman of the Department of Medicine. Requests for reprints should be sent to the Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA 94143.

Antineoplastic Agents↗
PubMed1982

The usefulness of the Lukes-Collins classification in identifying subsets of diffuse histiocytic lymphoma responsive to chemotherapy.

Twenty-nine patients with Stage III and IV diffuse histiocytic lymphoma (DHL) were treated prospectively with cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone and bleomycin (CHOP-B) or hydroxydaunorubicin, cyclophosphamide, vincristine, methotrexate with leucovorine rescue and cytosine arabinoside (ACOMLA). Twenty-six evaluable patients were reclassified blindly by the Lukes-Collins classification with five large noncleaved follicular center cell (FCC), six large cleaved FCC, three large cell unclassified, seven B-immunoblastic sarcoma and five T-immunoblastic sarcoma patients identified. There was no significant survival advantage between the two combination chemotherapy programs. Survival of the immunoblastic sarcoma patients was inferior to that of the FCC lymphoma patients (P = 0.02). There were no significant survival differences between the large cleaved FCC and noncleaved FCC subtypes. Immunoblastic sarcomas, B- and T-cell types, appear to be more resistant to standard combination chemotherapy programs and new approaches may warrant more aggressive therapy in future protocols. The large cell FCC lymphomas have an excellent prognosis.

Drug Administration Schedule↗
PubMed1982

Bone involvement in Hodgkin's disease.

Eighteen patients with osseous involvement were identified from a series of 124 consecutive patients treated with combined-modality therapy with advanced-stage or relapsing Hodgkin's disease. Multiple lesions were seen as frequently as were solitary lesions. Nodular sclerosing histology was as prevalent as mixed cellularity disease. However, those five cases initially diagnosed at protocol entry were predominantly mixed cellularity (80%) with multiple lesions (80%). Sites of involvement included: the spine, 24; pelvis, 8; ribs, 4; femur, 3; skull, 1; and shoulder 1. Actuarial survival for these patients was 84% at nine years. Only three patients were induction failures and no patient has had a relapse. Patients with bone lesions had favorable responses to combined-modality therapy.

Adolescent↗
PubMed1982

Splenectomy in Hodgkin's disease: no therapeutic benefit.

One hundred twenty-four patients with advanced Hodgkin's disease were treated uniformly with combination chemotherapy and radiotherapy. Splenectomy was not performed in 32 patients due to obvious stage IV disease, a medical contraindication, or patient refusal. Comparison of the splenectomy and nonsplenectomy patients revealed no differences in nadir white blood cell counts, platelet counts, or the total dosages of drugs that were administered. Survival and disease free survival curves with a 5-year median follow up also failed to show any difference in the two groups. Splenectomy does not offer a therapeutic advantage in those patients whose treatment would not be altered by splenic histology.

Antineoplastic Agents↗
PubMed1982

Randomized study comparing doxorubicin, cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (ACOMLA) with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-B) in the treatment of diffuse histiocytic lymphoma.

Two combination chemotherapy programs, ACOMLA (doxorubicin, cyclophosphamide, vincristine, methotrexate and leucovorin rescue, and cytarabine) and CHOP-B (cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin), were evaluated in 29 prospective randomized patients with advanced diffuse histiocytic lymphoma. A complete response was achieved in 13 of the 15 patients (87%) treated with CHOP-B and in nine of the 14 patients (64%) treated with ACOMLA. The overall complete response rate was 75%. Two patients treated with ACOMLA and none of the CHOP-B-treated patients have relapsed. Median followup is 32 months for ACOMLA patients and 26 months for CHOP-B patients. Actuarial freedom from relapse at 2 years is 49.9% for ACOMLA and 93.3% for CHOP-B (P = 0.04). Toxicity was substantial, with eight nonfatal episodes of sepsis and three drug-related deaths. There have been no central nervous system relapses. Although patients treated with CHOP-B have a better response rate, the small numbers of patients treated to date preclude definitive conclusions.

Antineoplastic Agents↗
PubMed1980

Biochemical evaluation of patients with cancer-associated hypercalcemia: evidence for humoral and nonhumoral groups.

In 50 consecutive patients with cancer-associated hypercalcemia, we measured nephrogenous cyclic AMP, tubular phosphorus threshold, fasting calcium excretion, plasma 1,25-dihydroxyvitamin D, and immunoreactive parathyroid hormone as determined by four region-specific antiserums. Nephrogenous cyclic AMP excretion was elevated in 41 patients and suppressed in nine (means, 5.85 vs. 0.51 nmol per 100 ml of glomerular filtrate). There was no overlap between these groups. When compared with 15 patients with primary hyperparathyroidism, the group with increased cyclic AMP excretion had similar reductions in tubular phosphorus threshold; higher fasting calcium excretion (means, 0.66 vs. 0.25 mg per 100 ml of glomerular filtrate, P < 0.01); marked reductions in 1,25-dihydroxyvitamin D (means, 20 vs. 83 pg per milliliter, P < 0.001); and lower levels of immunoreactive parathyroid hormone in all four assays. The data suggest that elevated excretion of nephrogenous cyclic AMP may be a useful marker of humorally mediated cancer-associated hypercalcemia, that this type of hypercalcemia is common, that the humoral factor responsible for this syndrome is not native 1-84 parathyroid hormone, and that the various subtypes of cancer-associated hypercalcemia are biochemically distinguishable from primary hyperparathyroidism.

Animals↗
PubMed1980

Curative potential of combined modality therapy for advanced Hodgkin's disease.

During the period from 1969 through 1977, 124 patients with advanced Hodgkin's disease underwent treatment with combination chemotherapy and radiotherapy. Sixty-three cases were previously untreated, and 61 were relapses following radical radiotherapy for localized Hodgkin's disease. No patient in this series had received prior chemotherapy. Of 102 patients (84%) who have entered complete remission, 92 remain in complete remission with a median follow up time of five years, 10 patients having relapsed, and acute leukemia having developed in 2. The cumulative survival rate for all 124 patients is 80% at five years; the relapse-free survival rate is 74%. In many, if not most cases, the Hodgkin's disease appears to be cured. We have also identified two subgroups of patients for whom the prognosis is worse than for patients with advanced-stage disease as a whole. Patients over the age of 40 years have a five-year survival rate of only 45%, compared with 89% for all other patients. Those Stage IV patients with multiple extranodal sites of involvement have a five-year survival rate of 48%, compared with 81% for other Stage IV patients with only a single extranodal site involved.

Adult↗
PubMed1979

High dose cytosine arabinoside (HDARAC) in refractory acute leukemia.

Thirteen leukemic patients with disease refractory to conventional chemotherapy were treated with 1.0 to 7.5 g/m2 of Cytosine Arabinoside (Ara-C) over 29 drug cycles. Drug infusions were spaced at 12-hour intervals; a maximum of four doses was administered over 36 hours. After single dose tolerance had been established, three or four dose cycles were given at 2- to 30-day intervals. There were three partial remissions (PR) and one complete remission (CR) in a treatment group of four patients with AML, five with ALL, two with lymphoma converted to leukemic phase, one CML in blast crisis, and one promyelocytic leukemia. Five of the patients were septic and considered terminally ill at the time of treatment. All other patients had evidence of drug responsiveness. The nadir of the white count occurred from 3 to 12 days after treatment, with subsequent recovery of the peripheral granulocyte count between days 12 and 28. Toxicity included nausea and vomiting (GI symptoms) in twelve patients, central nervous system (CNS) disturbances in eight patients, one episode of inappropriate antidiuretic hormone syndromes (SIADH), one of hyperuricemia, and fever in eleven patients. There was no evidence of hepatic or renal dysfunction. These high doses of Ara-C appear useful for treatment of patients with refractory leukemia. Hospitalization is brief and toxicity acceptable.

Acute Disease↗
PubMed1977

Acute nonlymphocytic leukemia: a delayed complication of Hodgkin's disease therapy: analysis of 109 cases.

The use of combined modality therapy (irradiation and combinations of drugs) in the treatment of Hodgkin's disease has produced a significant improvement in survival, during which most patients lead an active and productive life. The estimated 1% incidence of leukemia in treated Hodgkin's disease patients, however, is greater than would be expected in the general population. There is a vast amount of literature which indicates that alkylating agents, procarbazine and irradiation are leukemogenic and immunosuppressive in animals and man. It is than conceivable that the current intensive treatment programs which use these agents are promoting the development of acute non-lymphocytic leukemia (ANLL). This leukemia has occurred most often in patients whose Hodgkin's disease is poorly controlled and who have received more aggressive therapy. The latent period from the diagnosis of Hodgkin's disease to the diagnosis of leukemia is significantly shorter (p less than .0005) in those patients who have received intensive and near maximal radiotherapy (total nodal irradiation), combination chemotherapy (MOPP or equivalent) or a sequential combination of the two modalities than similar patients who were treated with less than total nodal irradiation and or single agent chemotherapy. The following characteristic features have occurred with sufficient frequency to suggest that the subsequent leukemia is a distinct clinicopathological entity: pancytopenia, megaloblastoid marrow, nucleated red blood cells in the peripheral blood, random chromosomal aberrations of the bone marrow in most patients (94%), and refractoriness to antileukemia therapy (response rate 6.5%) with a very short survival (median one month).

Acute Disease↗
PubMed1977

Hyperphosphatermia and hypocalcemia accompanying rapid cell lysis in a patient with Burkitt's lymphoma and Burkitt cell leukemia.

Hyperphosphatemia, hypocalcemia and acute oliguric renal failure resulting from uric acid nephropathy developed in a patient with Burkitt's lymphoma and Burkitt cell leukemia after effective chemotherapy. A review of other reported cases in which the patients had similar metabolic abnormalities is presented, and the pathophysiology is discussed. The clinical setting in which these metabolic developments are most likely to occur is defined, and an approach for their prevention and management is presented.

Acute Kidney Injury↗