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Biomedical subjects

B Moe

Publications and source records attributed to B Moe.

8 recordsLinked to original sources

Recombinant interferon-alpha combined with prednisone in metastatic renal cell carcinoma. Reduced toxicity without reduction of the response rate--a phase II study.

Five responses (lung metastases, three; lymph node metastases, two) were observed in 23 patients with metastatic renal cell carcinoma who received recombinant interferon-alpha-2A (IFN) 18 X 10(6) U in three intramuscular doses each week combined with oral prednisone (10 to 20 mg daily). The response duration was 4+, 4+, 9, 11+, and 15+ months. In general, the combination treatment of interferon and prednisone lead to a significant reduction of the subjective side effects (flu-like symptoms) as compared to a previous experience in patients treated with interferon only. Reduction of the interferon dose or discontinuation of IFN treatment was necessary in only two of 23 patients receiving IFN plus prednisone. Prednisone, however, had little effect on the hepatic toxicity often associated with high-dose IFN treatment. The subjective tolerability of a high dose of IFN is significantly increased if oral prednisone (10-20 mg) is given concomitantly in patients with metastatic renal cell carcinoma without reducing the response rate. Randomized trials will be necessary to confirm the efficacy of the IFN and prednisone combination. In addition, higher doses of IFN combined with prednisone should be evaluated in this malignancy.

Adult

Prediction of objective response to recombinant interferon-alpha with or without vinblastine in metastatic renal cell carcinoma.

Clinical, histopathological and DNA cytometric parameters were analyzed before treatment in 57 patients with metastatic renal cell carcinoma (RCC) with regard to their ability to predict objective response to treatment with interferon-alpha (IFN) with or without vinblastine (VB). No pretreatment factor could be identified which was correlated with response. Patients who had at least 30% size reduction of their indicator lesion(s) after 2 months and did not present with new visible metastases had a significantly higher chance to obtain objective response than those in whom this condition was not fulfilled. We suggest that interferon treatment (with or without VB) should be offered for 2 months to all patients with metastatic RCC who are to receive systemic therapy. If at least 30% tumour size reduction is observed at that time, the patient will most probably respond objectively. If the size reduction is less, IFN with or without VB is likely to be ineffective in terms of response achievement.

Adult

Recombinant interferon-alpha with or without vinblastine in metastatic renal carcinoma. Results of a randomised phase II study.

In a randomised phase II study, 5 of 24 patients with metastatic renal carcinoma responded to treatment with interferon (IFN) (Roferon A, Roche, Basle, Switzerland) (18 x 10(6) u i.m. 3 times/week). The combination of IFN with vinblastine (0.1 mg/kg every third week) yielded a response rate of 16% (4 of 25 patients). Three patients continue to show a response (2 complete, 1 partial) more than 20 months after cessation of treatment. Flu-like symptoms represented the major side effect and often led to modification or discontinuation of treatment. It was concluded that IFN is the treatment of choice in patients with metastatic renal carcinoma who are candidates for medical treatment. The significance of additional vinblastine is uncertain.

Antineoplastic Combined Chemotherapy Protocols

Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma.

Twenty patients with measurable metastatic renal cell carcinoma (RCC) were were treated with interferon alfa-2a (Roferon-A), 36 X 10(6)U intramuscularly 3 times weekly, alone (2 patients) or in combination with vinblastine, 0.10-0.15 mg/kg intravenously every 2 to 3 weeks. Objective responses in the lung, bone, liver, and lymph node metastases were seen in 6 of 18 evaluable patients. Dose reduction of interferon alfa-2a was necessary in 19 of the 20 patients due to intolerable flu-like side effects and fatigue. Bone marrow suppression and increase of gamma-GT represented the most often observed objective toxicity. The preliminary results of this combination treatment in RCC are promising and warrant randomized studies exploring the role of vinblastine. The dose of interferon alfa-2a should be reduced by 50% to avoid excessive toxicity and to maximize patient compliance.

Adult

Phase I/II tolerability/pharmacokinetic study with one-hour intravenous infusion of doxifluiridine (5'-dFUrd) 3 g/m2 VS 5 g/m2 QD x 5 per month.

Eighteen patients with advanced solid cancer were treated with daily 5'-dFUrd infusions given over 1 h on days 1-5 of a 4-week cycle. Nine patients received 3 g/m2 5'-dFUrd daily and another nine patients 5 g/m2. One patient on 5 g/m2 5'-dFUrd was not fully evaluable for tolerability due to early death (progressive disease) 4 weeks after the first cycle. A total of 48 cycles was given. The gastrointestinal and hematological toxicity was generally mild (grade 1-2). Central neurotoxicity (ataxia, unsteadiness, diplopia, dysarthria, sometimes confusion) was observed in 7 of 8 patients on 5 g/m2 5'-dFUrd leading to premature discontinuation of treatment in 3 patients (after 2 cycles). Only 3 of the 9 patients in the 3 g/m2 group had slight signs of cerebellopathy. Typically, the reversible neurological side effects started at the end of the 2nd week of a cycle. The serum elimination kinetics of 5'-dFUrd and its metabolites 5-FU and 5'-dFUH2 have been investigated in the serum and showed very low intra- and interindividual variations. Peak concentrations of the 5'-dFUrd at the end of the infusion approximated 500 mumol/l and 1000 mumol/l for the 3 g/m2 and 5 g/m2 group, respectively. The peak of the serum 5-FU was reached at the same time, the ratio 5-FU/5'-dFUrd being around 10%. The elimination half-life time for 5-FU was protracted by a factor of 2-3 compared with the direct injection of 5-FU. Monthly infusion of 5'-dFUrd 5 mg/m2 per day on days 1-5 lead to an unacceptable frequency and degree of neurological toxicity. Similar infusions of 5'-dFUrd 3 g/m2 per day on days 1-5 were well tolerated.

Adenocarcinoma

A mathematical model of parasystole and its application to clinical arrhythmias.

A ventricular parasystolic focus capable of generating manifest ectopic beats should not be totally insulated from the electrical events that accompany depolarization in the surrounding tissue; the intrinsic cycle length of the ectopic discharge may be modulated by electrotonic influences transmitted across the zone of "protection." To study the nature of the interaction, response patterns were examined in a mathematical model programmed to simulate an ectopic pacemaker protected, but not divorced from ventricular responses to the normal pacemaker. Computer runs covered a wide range of heart rates, and a wide range of magnitudes of the simulated electrotonic influence. Application of the results obtained in the model to published examples of complex arrhythmias revealed a remarkably close fit to many clinical examples. This findings suggests that many patterns attributed to a re-entrant "extrasystolic" rhythm may, in fact, represent the modulated activity of a parasystolic focus.

Arrhythmias, Cardiac

Interaction of sequential stimuli applied during the relative refractory period in relation to determination of fibrillation threshold in the canine ventricle.

An ineffective stimulus applied to cardiac tissue within the relative refractory period can alter the response to an immediately subsequent stimulus. We observed three response patterns that can coexist at different sites of stimulation in the same heart. In the first pattern, a stimulus of two to ten times diastolic threshold, applied too early to elicit a propagated response, becomes effective when a stimulus of equal strength is delivered 10 msec earlier. In the second pattern, a stimulus applied just late enough to evoke a response fails to do so when a stimulus of equal strenght precedes it by as much as 30 msec. Finally, in the third pattern, two stimuli, separated by 10 msec, both of which are late enough to be effective when they are given alone, fail to yield a propagated response when they are applied together. These results have a bearing on the use of trains of stimuli to assess the ventricular fibrillation threshold. Possible interpretations are based on the temporal dispersion of recovery from the refractory state.

Animals