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Biomedical subjects

S Eckhardt

Publications and source records attributed to S Eckhardt.

At least 91 records · Page 5Linked to original sources
PubMed1982

Dibromodulcitol plus bleomycin compared with bleomycin alone in head and neck cancer.

Advanced recurrent squamous cell head and neck cancer patients were prospectively randomized to receive or not receive dibromodulcitol 10 mg/kg PO weekly for 8 consecutive weeks in addition to bleomycin chemotherapy. Patients initially entered in the study received bleomycin 15 mu/m2 three times weekly for 8 weeks. This was later changed to 15 mu/m2 twice weekly for 8 weeks because of unacceptable stomatitis. Most patients had relapsed following surgery and/or radiotherapy, but none had received prior chemotherapy. A2 : 1 randomization in favor of the dibromodulcitol-containing therapy was used. There were 12 partial responses in the 44 evaluable patients receiving the combination (27%), and 4 partial responses in the 18 patients receiving single-agent bleomycin chemotherapy (22%). This difference was not statistically significant. Response durations were also relatively short for both therapies. Within the limitations of this study, we were unable to demonstrate that patient benefit resulted from the addition of dibromodulcitol to bleomycin chemotherapy for this patient population.

Adult↗
PubMed1982

Metabolism and pharmacokinetics of dibromodulcitol (DBD, NSC-104800) in man--II. pharmacokinetics of DBD.

Dibromodulcitol (DBD), labelled with [3H] at position C-1, was administered orally to 6 patients in a single dose of 15 mg/kg. Kinetic parameters were calculated for the effective drug (DBD + BrEpG + DAG), protein-bound hexitol moieties and free metabolites. Approximate values were estimated for the oral bioavailability of DBD. Disposal of the drug by metabolism and excretion was described by a simplified catenary model. The results indicated that 8-20% of the drug became firmly bound to macromolecules, probably by alkylation. The slow rate of alkylation in vivo (half-life 14 hr) may imply conversion of DBD into epoxides and their alkylating interaction with the target nucleophiles. The long retention of the firmly bound hexitol moieties in the body may be an indicator of the cumulative potency of DBD and must be taken into consideration by developing dosage schedules.

Administration, Oral↗
PubMed1980

Chemical reactivity and intracavitary application of alkylating sugar alcohol derivatives.

Lycurium [1,4-di-(methylsulfonyloxy-ethylamino)-1,4-didesoxy-erythrioldimethylsulfonate; R-74; NSC-122402] undergoes rapid hydrolysis in aqueous solutions. The concentration of the alkylating compound(s), demonstrated by the 4-(4'-nitrobenzyl)pyridine reaction, decreases approximately by 80% in 10 min following the dissolution of the drug in saline. In patients peak plasma concentration of radioactivity after the intracavitary injection of 14C-labelled Lycurim is observed between 4 and 6 h. It is assumed, therefore, that only a negligible amount of pharmacologically active alkylating compounds reaches the circulation after intracavitary application. This conclusion is supported by clinical experience showing that intracavitary administration of the same amount of Lycurim causes much milder systemic side-effects than intravenous injection. A dose escalation study was started to determine the applicability of Lycurim in the form of high volume intraperitoneal instillation ('belly bath') for the treatment of ovarian cancer.

Drug Stability↗
PubMed1980

Forms and results of mitolactol therapy.

The authors give a summarizing report about mitolactol treatments performed in Hungary. As a single-agent therapy the drug was administered in two forms: (1) every-day therapy, 5 mg/kg/day, (2) push therapy, 10 mg/kg every 5th day or 15 mg/kg every 7th day, in a total dose of 100 mg/kg in both administration forms. Out of the solid tumours the squamous cell cancers proved to be the most responsive to mitolactol therapy: first of all in tumours of the head and neck and of the lung. The study also reports the preliminary results of polychemotherapeutical protocols containing mitolactol now in progress: (1) bleomycin + mitolactol (Bristol protocol), (2) carminomycin + mitolactol and (3) adriamycin + mitolactol.

Dose-Response Relationship, Drug↗
PubMed1980

Future clinical perspectives. A concluding discussion.

Since there are considerable differences between animal models and human malignancies, new test systems are required for selecting effective antitumor drugs, such as T cell-deprived or nude mice, capable of hosting human tumor xenografts. Study of target determinants of drug action in normal and malignant cells is a promising approach for selecting proper drugs. In order to accomplish this task, cell separation techniques have to be further developed. Samples of human malignant cells need to be identified by morphological, biochemical and genetical markers. Clinicians face the problem of treating tumors individually. Malignant cells in leukemias and metastatic fluids can be successfully analyzed in respect of their drug sensitivity. It is expected that in the case of solid tumors similar attempts will result in a more rational therapeutic approach as well.

Animals↗
PubMed1980

Clinical trials with MTDQ /6,6'-methylene-bis (2,2,4-trimethyl-1,2-dihydroquinoline)/ an antioxidant with radiation sensitizing effect.

Daily doses of 1320 mg MTDQ have been administered orally to 7 patients for 100 subsequent days. Biological half-life and serum concentration measurements were performed. Function of vital organs, as well as routine laboratory findings revealed that MTDQ did not induce any toxic changes. The effect of MTDQ on the radiosensitivity of hypoxic tumor cells was studied in a combined treatment modality including 12 patients. The action on tumor regression was found encouraging. It has been found remarkable, too, that due to the effect of MTDQ and radiotherapy some of the nonspecific and general symptoms (e. g. pruritus) also disappeared.

Clinical Trials as Topic↗
PubMed1980

"Diclonal" gammopathies.

Eleven patients with "diclonal" gammopathies have been followed clinically and cytologically in relation to the changes in their serum protein composition. It was observed that the malignant transformation became faster after a second protein had appeared with the appearance of immature lymphoid elements and plasmoblasts. Malignant transformation may occur after long periods of stagnation, therefore a continuous observation of such cases is mandatory.

Aged↗
PubMed1979

Basal cell carcinoma treated with MTDQ and irradiation.

Patients with basal cell carcinoma of the skin were treated with combined MTDQ (6,6'-methylene-bis-(2,2,4-trimethyl-1,2-dihydroquinoline)) administration and irradiation. Significantly better results were obtained with a skin exposure of 2 000 R combined with MTDQ than with the same dose alone. The results were comparable to those obtained with an exposure of 4 000 R. MTDQ administration induced decrease of tissular malonaldehyde concentration and suggested the peroxide-decomposing action of the radiation sensitizer.

Adult↗