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Biomedical subjects

B A Chabner

Publications and source records attributed to B A Chabner.

At least 37 records · Page 2Linked to original sources
PubMed1978

Sequential nonsurgical and surgical staging of non-Hodgkin's lymphoma.

The results of clinical and surgical staging in a series of 170 patients with non-Hodgkin's lymphoma are reviewed. Advanced disease (Stage IV) was established without laparotomy in 95 patients (56%), primarily through bone marrow biopsy, closed liver biopsy, and peritoneoscopy. Laparotomy revealed a high incidence of liver involvement and involvement of lymph nodes outside of conventional abdominal irradiation portals only in patients with nodular types of pathology and in patients with positive lymphangiograms. The limitations and indications for staging laparotomy are discussed in the context of these findings.

Biopsy↗
PubMed1978

Hexamethylmelamine in alkylating agent-resistant ovarian carcinoma.

Twenty-one patients with advanced ovarian cancer proven resistant to standard alkylating chemotherapy were evaluated in a prospective study of Hexamethylmelamine. All but three patients received 8 mg/kg daily with dose modifications appropriate to the degree of toxicity; the latter three patients were treated on an intermittent 14 day course of 8 mg/kg daily. Six patients (28%) experienced an objective response with a median duration of 2.5 months (range 1--5 months). The toxic effects requiring dose modification were gastrointestinal in 57%, hematologic in 62%, and neurologic in 28.5%. An average of 60.5% of the total projected dose was tolerated for a median of 44 days (range 7--113). Twelve patients (57%) experienced severe toxicity requiring discontinuation of therapy. It is apparent from this study that Hexamethylmelamine is an active agent in ovarian cancer and is not invariably cross-resistant to conventional alkylating agent therapy. These two characteristics make it an attractive agent for use in combination. Its toxicity in previously treated patients in the schedules used here, however, is substantial.

Adenocarcinoma↗
PubMed1978

Initial clinical trials of maytansine, an antitumor plant alkaloid.

We have conducted a phase I clinical trial of maytansine, a plant alkaloid with potent tubulin-binding activity. For evaluation of toxicity, the schedule of drug administration consisted of a single iv infusion given every 3 weeks. Dose-limiting toxicity was observed at 2 mg/m2, and was manifested as profound weakness, diarrhea, nausea, and vomiting. Symptoms persisted for 3--14 days after drug administration. No consistent myelosuppression occurred at any dose level. Responses were observed in two patients (one each with non-Hodgkin's lymphoma and ovarian cancer) who were treated on the every-3-week schedule, as well as in two patients with acute lymphocytic leukemia treated with single weekly doses. Three of the four responding patients had received extensive prior treatment with vincristine, and two were clearly resistant to vincristine.

Adolescent↗
PubMed1978

Chemotherapy (cyclophosphamide, vincristine, and prednisone) versus radiotherapy (total body irradiation) for stage III-IV poorly differentiated lymphocytic lymphoma.

Seventy-two patients with stage III-IV malignant lymphoma of the poorly differentiated lymphocytic (PDL) type were randomly assigned to initial chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP) or to radiotherapy with total body irradiation (TBI). The response and survival rates were similar for CVP and TBI in patients with nodular PDL, with 66% and 67%, respectively, surviving at 7 years. Induction treatment with TBI yielded better response and early survival than CVP for patients with diffuse PDL but a survival advantage did not exist at 5 years, the survival rate being 28% and 25%, respectively. TBI was more easily tolerated than CVP as initial therapy, 19 (51%) of the 37 CVP patients had a complication which required hospitalization during the first six cycles as contrasted to only one of 35 patients receiving TBI who required hospitalization. Most chemotherapy complications were infectious in nature, secondary to relatively severe granulocytopenia, and one patient died from Candida sepsis following the first cycle of CVP. Late complications consisted of two TBI patients who developed a myeloproliferative disorder and two CVP patients who experienced persistent disabling neurotoxic reactions. Durable remissions were not achieved with significant frequency using either form of treatment, indicating a need to evaluate new therapeutic approaches for the management of PDL lymphoma.

Cyclophosphamide↗
PubMed1977

Use of plasma pharmacokinetics to predict and prevent methotrexate toxicity.

To correlate the pharmacokinetics and toxicity of methotrexate, we measured the drug's clearance from plasma after 395 high-dose, six-hour infusions given to 78 patients. After 375 infusions, 48 hour methotrexate levels fell within 2 standard deviations of the mean for nontoxic infusions, and myelosuppression did not occur. Methotrexate concentrations exceeded the range for nontoxic patients (mean +/- 2 standard deviations) after 20 infusions. Serious myelosuppression occurred after six of these 20 infusions, including five of 12 infusions associated with 48-hour drug concentrations above 9 X 10(-7) M. In seven patients with 48-hour concentrations above 9 X 10(-7) M, the absence of toxicity could be attributed to subsequent rapid clearance of the drug; four of these patients also received large doses of supplemental leucovorin (50 to 100 mg per square meter every six hours). Determination of methotrexate concentration in plasma thus identified patients at high risk of toxicity, a group that may benefit from supplemental leucovorin rescue.

Blood Cell Count↗
PubMed1977

Cyclic nucleotide phosphodiesterase and protein activator in human cancer cell lines and Brown-Pearce carcinoma.

3':5'-Cyclic-AMP phosphodiesterase (EC 3.1.4.17) and the activating factor of cyclic nucleotide phosphodiesterase were detected in cultured human cell lines from patients with lymphoblastic leukemia and retinoblastoma and in the Brown-Pearce (rabbit) carcinoma. The homogenate of lymphoblasts contained levels of the activating factor in excess of that required to produce maximal activation of the endogenous phosphodiesterase. The activating factor found in these malignant cells appears to be similar to the calcium-binding protein activator of bovine brain phosphodiesterase on the basis of the molecular weight obtained from gel filtration, electrophoretic patterns, calcium requirement for the activity, and the effect of calcium on the proteolysis. In addition, the tumor-derived activator was able to restore the activity of activator-deficient phosphodiesterase from the bovine brain.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1977

Lymphoma presenting in bone: results of histopathology, staging, and therapy.

Lymphoma presenting in bone (that is "reticulum cell sarcoma of bone") is a form of extranodal lymphoma historically described as frequently localized (this is, stage IE or stage IIE). Between 1970 and 1975, 14 patients with this entity were seen at the National Cancer Institute. This group had a variety of histologic subtypes of diffuse lymphoma. Thorough staging showed extensive disease (stage IV) in 12 of these patients (86%). In 10 of these the metastatic disease was unsuspected clinically. Seven patients achieved complete remissions after treatment was combination chemotherapy alone (two patients), irradiation alone (one patient), surgery alone (one patient), and both chemotherapy and irradiation (three patients) and are alive and free of disease 11 + to 70 + months after diagnosis. The other seven patients did not achieve complete remission status and have all died. Although lymphomas presenting in bone may occasionally be localized, careful staging in this series frequently showed extensive disease and altered the therapeutic approach.

Adolescent↗
PubMed1977

Peritoneoscopy: a technique to evaluate therapeutic efficacy in non-Hodgkin's lymphoma patients.

Peritoneoscopy was performed in 22 patients with non-Hodgkin's lymphoma as a re-staging technique to rule out relapse or persistence of active disease after intensive chemotherapy and/or radiotherapy. Fifteen patients with previous hepatic involvement achieved a complete clinical remission; however, five patients (33%) had persistent disease proved by biopsy at peritoneoscopy. In seven patients suspected to have a clinical relapse, peritoneoscopy biopsies documented relapse in three patients (43%), including two patients with negative percutaneous liver biopsies. Because of its low morbidity rate (4%), peritoneoscopy can be utilized to re-stage hepatic involvement by non-Hodgkin's lymphoma patients more accurately than percutaneous liver biopsies and with less morbidity than laparotomy.

Humans↗
PubMed1977

Advanced lymphocytic lymphoma: randomized comparisons of chemotherapy and radiotherapy, alone or in combination.

Ninety-nine previously untreated patients with stage III and IV malignant lymphoma were randomized to receive either cyclic combination chemotherapy (50 patients) or extensive "systemic" radiotherapy (49 patients). Histologic classification included nodular poorly differentiated lymphoma (54 patients), nodular mixed lymphoma (21 patients), and diffuse poorly differentiated lymphoma (24 patients). High overall response rates were seen with either approach (90% for radiotherpy; 86% for chemotherapy) and complete remission were relatively common (60%--80%). Overall median survival of all patients in this trial will exceed 5 years regardless of the induction therapy used; however, disease-free survival is not commonly achieved with either regimen. Relapse-free survival rates at 4-year followup, regardless of induction regimen, are 13% for diffuse lymphomas and 24% for nodular lymphomas. The second prospective trial attempts to use a combined approach and compares cyclic combination chemotherapy with total-body irradiation and combination chemotherapy. Initial results on 34 patients indicate high overall response rates (100%) and similar complete remission rates (64%--67%). With 14 months' median followup no patients in either arm of the trial have died but relatively equal numbers have relapsed.

Adult↗
PubMed1977

Dose-dependent metabolism of methotrexate in man and rhesus monkeys.

Humans and rhesus monkeys receiving high-dose methotrexate (MTX) (greater than 50 mg/kg) excrete significant quantities of the metabolite, 7-hydroxy-MTX. This metabolite, though 200-fold less potent than MTX as an inhibitor of mammalian dihydrofolate reductase, is of very limited aqueous solubility, and thus may contribute to the renal toxicity of the high-dose regimen. The metabolite was not observed in previous pharmacologic studies in which conventional doses of MTX were administered (less than 10 mg/kg).

Adolescent↗