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Biomedical subjects

R M Bukowski

Publications and source records attributed to R M Bukowski.

At least 163 records · Page 9Linked to original sources

Phase II trial of streptozotocin, mitomycin C, and 5-fluorouracil in adenocarcinoma of the pancreas.

A phase II study study employing 5-fluorouracil, mitomycin C, and streptozotocin in unresectable pancreatic carcinoma was performed. Seven of 22 patients (32%) responded and 4 of 22 (18%) had stable disease. Median survival of the entire group was 6 months, and of responders 9.5 months. In 13 patients with localized disease, five responses (38%) were seen and median survival was 7.5 months. Toxicity of the regimen was moderate, being predominantly gastrointestinal and renal. The usefulness of this regimen in localized pancreatic cancer should be explored further.

Adenocarcinoma↗

Prognostic factors affecting remission, remission duration, and survival in adult acute nonlymphocytic leukemia.

The medical records of 94 consecutive patients with acute nonlymphocytic leukemia (ANLL) were reviewed to identify significant prognostic factors. The data were analyzed using 1) Cox's linear hazard and linear logistic models, 2) chi-square comparison of the groups living longer than 2 years and those living less than 2 years, and 3) the Gehan-Breslow test of equal survival curves. The only statistically significant finding was that the presence of promyelocytic cell type and complete remission correlated with increased survival (p less than .05), but this was negated by the small number of patients with this cell type. There was a suggestive association between higher initial hemoglobin and survival (p = .09). The Gehan-Breslow test revealed a possible difference in survival between those patients more than 51 years of age and those less than 51 (p = .10). Thus none of the commonly accepted prognostic factors in acute nonlymphocytic leukemia was definitely shown to be useful. The findings of this study support an aggressive approach toward all patients with this disease.

Adolescent↗

Combination chemotherapy for islet cell carcinoma and metastatic carcinoid tumors with 5-fluorouracil and streptozotocin.

The results of combination chemotherapy with intermittent courses of 5-fluorouracil and streptozotocin in ten patients with metastatic carcinoid tumors and in eight patients with islet cell carcinoma are reported. Objective responses occurred in two of ten and in two of seven evaluable patients respectively. Biochemical responses occurred in an additional two patients with carcinoid. No improvement over single-agent chemotherapy and no effects on survival were noted.

Adenoma, Islet Cell↗

Immunotherapy of disseminated renal cell carcinoma with transfer factor.

Ten patients with disseminated renal cell carcinoma have been treated with transfer factor as an immunostimulant. In 5 patients with metastatic disease evident at the time of initial diagnosis treatment involved removal of the primary tumor followed by transfer factor therapy. Of these patients 3 had a temporary stabilization of metastatic disease. Three patients with recurrent metastatic disease after previous nephrectomy were treated, 2 of whom showed a temporary stabilization of metastatic disease. There were 2 additional patients without clinically evident metastases but at a high risk for recurrent disease who were treated and remain free of disease. We used 5 immunologic parameters to evaluate the clinical effects of transfer factor. No objective clinical regression was noted in any patient treated with measurable disease.

Adenocarcinoma↗

Plasmapheresis in the treatment of thrombotic thrombocytopenic purpura.

Two patients with thrombotic thrombocytopenic purpura (TTP) have recovered completely after intensive plasmapheresis. The mechanisms responsible for the improvement in these instances are most likely related to the removal of an inciting or damaging agent. The possibility that this agent may be an immune complex is discussed. Plasmapheresis appears to be useful therapy for some patients with this syndrome.

Adult↗

Nonspecific lymphocyte cytotoxicity in patients with malignant melanoma, renal cell carcinoma, and sarcomas, and in nontumor patients.

Mononuclear cell-mediated tumor cell destruction was studied in 114 patients with malignant melanoma, renal cell carcinoma, or sarcomas, and in 122 non-tumor-bearing control subjects, with the use of the microcytoxicity assay. Cytotoxic reactions were found in all patients and control groups against melanoma, renal carcinoma, sarcoma, and fibroblast-derived cell cultures; mean levels of cytotoxicity against allogeneic combinations of tumor cells and fibroblasts were similar in tumor-bearing and control patients. These results support the concept that the reactions found represent nonspecific cytotoxicity.

Adenocarcinoma↗

SPLEEN/PATHOL.

Lymphocyte subpopulations were studied in the peripheral blood, lymph nodes, and spleens in a group of 17 patients with untreated Hodgkin's disease. In 12 of 15 cases, diminished absolute levels of T-lymphocytes in the peripheral blood were found; however, this was correlated with total lymphopenia. No direct relationship between "T-lymphopenia" and diminished cellular immunity, as measured by phytohemagglutinin and pokeweed mitogen blast transformation, and delayed cutaneous hypersensitivity was demonstrated. In eight lymph nodes involved histologically by Hodgkin's disease, a preponderance of T-lymphocytes was found when compared with a group of seven hyperplastic nodes (78.2 +/- 8.9% versus 54.5 +/- 11.0%, P is less than 0.01). These latter data appear to be consistent with the hypothesis that the pathogenesis of Hodgkin's disease involves a cell-mediated immune response to a neoplastic (antigenic) element.

B-Lymphocytes↗

Polyethylene glycol conjugated interleukin-2: clinical and immunologic effects in patients with advanced renal cell carcinoma.

Recombinant interleukin-2 (rIL-2) modified with monomethoxypolyethylene glycol (PEG IL-2) was utilized in patients with metastatic renal cell carcinoma in two separate multi-institutional trials. PEG IL-2 was administered as an I.V. bolus days 1, 8, 15, and 22 with cycles repeated every six weeks. The two trials employed different dose levels: A) 20 x 10(6) I.U./m2 day 1 followed by 12 x 10(6) I.U./m2 days 8, 15, 22; and B) 12 x 10(6) I.U./m2 days 1, 8, 15, 22. Thirty-five patients were entered and 31 were evaluable for response (A-15/18, B-16/17). Two of 31 patients had partial responses. Median therapy duration was four weeks (range 1-15), and dose reduction for grade III or IV toxicity was required in 14/35 patients (A-6/18, B-8/17). Toxicity (> or = grade III) seen included: hypotension 51%, dyspnea 17%, seizures 6%, and mental status changes 11%. No differences in response or toxicity between the two schedules were noted. Hematologic changes included lymphocytosis and eosinophilia in the majority of patients. PEG IL-2 given once weekly has significant toxicity, and may produce tumor regression in patients with renal cell carcinoma.

Adult↗

Phase 1 trial of subcutaneous IL-6 in patients with refractory cancer: clinical and biologic effects.

The authors evaluated the clinical and biologic effects of human recombinant interleukin-6 (rhIL-6) in patients with refractory cancer. A phase 1 trial using escalating doses of rhIL-6 (1-50 microg x kg(-1) x d(-1), Monday through Friday for 4 weeks) was performed in 30 patients. Toxicity was moderate and the maximum tolerated dose was determined to be 25 microg x kg(-1)x d(-1) based on cardiac and neurocortical toxicity in one patient each and thrombocytosis (platelets > 800,000/microL) in three patients. One patient with non-small-cell lung cancer had a partial response after three cycles of therapy. The biologic effects of rhIL-6 included anemia and dose-related thrombocytosis. Various proinflammatory activities were induced and included dose-related cyclical increases in peripheral blood monocytes and the CD14+/CD45RB+ +/- CD16C+ mononuclear cell populations. These increases were accompanied by increased levels of C-reactive protein, serum neopterin, and type I soluble tumor necrosis factor receptor. In contrast, rhIL-6 did not affect lymphocyte numbers or function (cytotoxicity, cytokine levels, immunoglobulin levels), with the possible exception of IL-2Ralpha mRNA induction in peripheral blood lymphocytes. rhIL-6 has pleiotropic proinflammatory actions in vivo and moderate toxicity when administered as long-term therapy.

Acute-Phase Reaction↗

Carcinoid myopathy.

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Electromyography↗

Hepatic artery infusion chemotherapy for colorectal liver metastases.

Twenty-two patients with hepatic colorectal metastases had Infusaid pumps implanted for hepatic artery infusion chemotherapy, or HAIC. Prior to pump placement, 19 of the 22 patients received percutaneous HAIC with 5-fluorouracil and citrovorum factor. Floxuridine, 0.2 mg/kg/d, was administered via the Infusaid pump and was alternated with saline solution every 2 weeks. HAIC responsiveness was defined as a 50% or greater reduction in the sum of all diameters of measured lesions on computerized tomography scans and no evidence of extra-hepatic tumor. Nine patients (41%) had a favorable response to HAIC; four (18%) had a partial response to percutaneous HAIC and five (23%) were considered pump responders. All responders had pretreatment liver replacement of less than 50%. The mean survival after pump placement was 13.6 months for responders and 11.1 months for non-responders. Although there were no operative deaths, the morbidity rate was 36%, and 31% of patients manifested significant chemotherapy toxicity. While toxicity is not insignificant and there is no survival benefit, the Infusaid pump is a reliable drug delivery system for HAIC, and may result in regression of colorectal liver metastases in patients with less than 50% hepatic replacement.

Antineoplastic Combined Chemotherapy Protocols↗