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Biomedical subjects

B Samuels

Publications and source records attributed to B Samuels.

59 records · Page 4Linked to original sources
PubMedDate not supplied

Phase II trial of uracil/tegafur (UFT) plus leucovorin in patients with advanced hepatocellular carcinoma.

UNLABELLED: Although UFT 300 mg/m2/day and leucovorin 90 mg/day administered orally in divided doses administered every 8 hours for 28 days repeated every 35 days could be administered safely to patients with advanced hepatomas and good performance status, this combination and schedule has limited activity in treating advanced hepatoma. BACKGROUND/PURPOSE: Biochemical modulation of 5-fluorouracil has yielded higher response rates in hepatoma when compared to treatment with 5-fluorouracil as a single agent, although the impact on survival has been negligible. This study was conducted to determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration ratio (UFT; Bristol-Myers Squibb, Wallingford, CT) plus oral calcium leucovorin in the treatment of patients with advanced hepatocellular carcinoma (hepatoma). PATIENTS AND METHODS: Sixteen patients with advanced measurable hepatocellular carcinoma were enrolled onto the trial. All patients had a Karnofski performance status > or = 60%, platelet count > or = 75,000/micro L, total bilirubin < or = 2.0 x institutional upper limit of normal but otherwise normal liver and kidney function profile and bidimensionally measurable disease by CT or ultrasound examination. None of these patients received prior cytotoxic chemotherapy or radiation therapy for advanced disease. Fourteen patients received 300 mg/m2/d UFT plus 90 mg/d leucovorin administered orally in divided daily doses every 8 hours for 28 days repeated every 35 days. Two patients registered for the trial but did not receive study medication. Objective tumor response, the primary purpose of this trial, was evaluated after two courses of therapy. Other end-points included toxicity, time to progression, and overall survival. RESULTS: Fourteen patients were evaluable for response and toxicity, respectively. No complete or partial responders were observed in this trial. Three patients had stable disease lasting 17 to 22 weeks. Toxicity was mild with severe (grade 3 or 4) liver pain, diarrhea, anorexia/nausea, fatigue, dyspnea, hyperbilirubinemia, anemia, and edema seen in 3 (21%), 2 (14%), 3 (21%), 2 (14%), 1 (7%), 1 (7%), 1 (7%) and 1 (7%) patients, respectively. The most frequent grade I and 2 toxic effects included fever of unknown origin, dyspnea, nausea, vomiting and diarrhea. CONCLUSION: UFT 300 mg/m2/d plus oral leucovorin 90 mg/d administered for 28 days did not demonstrate antitumor activity against advanced hepatomas. Further treatment using this regimen is not recommended for this disease.

Adult↗
PubMedDate not supplied

Phase I dose-escalation study of tumor necrosis factor-alpha and concomitant radiation therapy.

PURPOSE: Tumor necrosis factor-alpha enhances x-ray killing of human tumor cells in vitro and enhances tumor control when combined with radiation in animal tumor models. To determine the toxicity and maximal tolerated dose of tumor necrosis factor-alpha given daily during radiotherapy, we conducted a phase I dose-escalation study combining tumor necrosis factor-alpha and radiation. PATIENTS AND METHODS: Thirty-one patients, including 14 patients with locally advanced primary tumors and 17 patients with metastatic sites, were entered into this study. Recombinant human tumor necrosis factor-alpha was administered intravenously at doses ranging from 10 microg/m2 to 150 microg/m2 4 hours prior to each radiation therapy session, which was given on consecutive days for a minimum of 2 weeks. Radiation was prescribed to localized fields, with dose fractions ranging from 150 to 300 cGy/day for palliation or control of locally advanced tumors. RESULTS: Major toxicity requiring withdrawal from the study was independent of tumor necrosis factor-alpha dose and occurred in seven patients. Symptoms included angina in two patients, and hypotension, respiratory distress, atrial fibrillation, allergic reaction, and progressive leukopenia in one patient each. A tumor necrosis factor-alpha dose of 150 microg/m2 was the maximum dose administered. No single dose-limiting toxicity was observed and a maximal tolerated dose could not be defined. There was no obvious increase in in-field toxicity. Response to treatment was assessed in 20 patients. Complete regression within the irradiated field was achieved in four patients, partial regression in four, and a minimal response in four. A trend toward a greater response rate at higher doses of tumor necrosis factor-alpha was observed. CONCLUSIONS: The maximal tolerated dose of tumor necrosis factor-alpha when given with radiotherapy is at least 150 microg/m2 and a dose-limiting toxicity was not observed. Future studies will show whether responses to treatment are increased over those expected with radiation alone. Tumor localization of tumor necrosis factor-alpha by gene therapy combined with radiation therapy may eliminate the systemic toxicity we observed.

Adult↗