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S Dische

Publications and source records attributed to S Dische.

At least 73 records · Page 4Linked to original sources
PubMed1985

Chemical sensitizers for hypoxic cells: a decade of experience in clinical radiotherapy.

The clinical work with chemical agents to restore the radiosensitivity of hypoxic cells began in 1973 with metronidazole, misonidazole was first given in 1974. The results so far recorded of the clinical trials with misonidazole have been generally disappointing. Only in 5 of 32 studies analyzed have significant benefits been shown to suggest real advantage with the use of misonidazole. Hypoxic cells must exist in all human tumours presenting for treatment and it is, however, probable that the oxygen effect is an important one at all dose fractionation regimes employed in radiotherapy but, after conventional fractionated radiotherapy, hypoxia may be a reason for failure in only a proportion of cases. The most important factor underlying the failure of misonidazole to achieve useful advantage is undoubtedly the low radiosensitizing concentrations achievable with the permitted dose of this neurotoxic drug. New drugs are under development and some have different dose-limiting toxicity. Those showing promise at this time are the Stanford compound, SR-2508, which is being extensively studied in the United States and the Roche compound, Ro 03-8799, which is being studied in the United Kingdom. It is possible that the greatest sensitization with the greatest tolerance will be achieved by a combination of drugs.

Adrenal Cortex Hormones↗
PubMed1978

Hyperbaric oxygen and radiotherapy: a Medical Research Council trial in carcinoma of the cervix.

In a randomized controlled clinical trial of hyperbaric oxygen in the radiotherapy of advanced carcinoma of the uterine cervix a total of 320 cases were contributed by four radiotherapy centres in the United Kingdom. The use of hyperbaric oxygen resulted in improved local control and survival. The benefit was greatest in patients under the age of 55 who presented with stage III disease. There was a slight increase in radiation morbidity but it seemed that the benefit of hyperbaric oxygen outweighed this increase in morbidity and that there was a true improvement in the therapeutic ratio.

Adult↗
PubMed1978

Hyperbaric oxygen: the Medical Research Council trials and their clinical significance.

The clinical trials of the use of hyperbaric oxygen in radiotherapy conducted by the Medical Research Council's working party have shown that local cure and survival can be improved in head and neck and cervical cancer. Evidence for benefit has been presented in carcinoma of bronchus, but none has so far been found in carcinoma of the bladder. Although hyperbaric oxygen has produced increased effect upon normal tissues as well as upon tumour, a real improvement in therapeutic ratio appears to be present. The future use of hyperbaric oxygen in radiotherapy will depend upon a comparison of effectiveness with other methods now being tested to improve radiotherapy. The trials have yielded much fundamental and clinical data of general relevance in the radiotherapy of malignant disease.

Bronchial Neoplasms↗
PubMed1978

The neurotoxicity of misonidazole and its relationship to dose, half-life and concentration in the serum.

Misonidazole has been given to a total of 87 patients. Neurotoxicity has occurred--convulsions with the higher doses and peripheral neuropathy with the lowern ones. The data from 34 patients receiving 4--7 doses has been analysed. Peripheral neuropathy is related to the total tissue exposure. By monitoring serum levels and controlling the total dose given, convulsions are avoidable and peripheral neuropathy restricted to a low and acceptable level.

Drug Administration Schedule↗
PubMed1978

The optimum regime for the administration of misonidazole and the establishment of multi-centre clinical trials.

The amount of misonidazole which may be given to one patient is limited because of the risk of neurotoxicity. The drug may be given with every treatment of a multi-fraction course of radiotherapy or only with some of the treatments. The number of radiotherapy treatments can be reduced or multiple treatments given after each dose of the drug. Experience in 19 patients given daily doses of misonidazole is reported. This is practical regime to be considered for clinical trials of this hypoxic cell sensitizer.

Drug Administration Schedule↗
PubMed1978

Clinical experience with misonidazole.

A total of 62 patients with advanced tumours have now been treated by a fractionated course of radiotherapy, with misonidazole. The prime purpose of the administration of the drug to these patients was to determine safe dosage and suitable regimes for use in clinical radiotherapy. The reaction of normal tissues did not seem enhanced but there was an impression of increased tumour response.

Digestive System↗
PubMed1977

Clinical testing of the radiosensitizer Ro 07-0582: experience with multiple doses.

The hypoxic cell radiosensitizer, Ro 07-0582, has now been given in multiple doses to 16 patients. They have received a total of 15-51 g in 3-20 doses. Immediate tolerance was good, and satisfactory plasma levels of the drug were consistently obtained. Neurotoxicity was, however, troublesome: convulsions occurred in the patient given the highest dose, and there was peripheral neuropathy in 11 cases. Tumour concentrations similar to those in plasma were obtained in human tumours, in contrast to the findings in mouse tumours where concentrations are usually below 40% of plasma levels. In the treatment of human tumours, a lower dose of Ro 07-0582 should give useful hypoxic cell sensitization. Although the total dose of Ro 07-0582 must be limited, there is a real prospect that it will give benefit in clinical radiotherapy.

Adult↗
PubMed1976

Hypoxic cell sensitisers in radiotherapy.

Solid tumours contain poorly oxygenated cells, and these are disproportionately resistant to therapeutic radiation. Several methods of overcoming this problem have been used clinically, including the administration of hyperbaric oxygen during irradiation, radiotherapy with heavy nuclear particles such as neutrons from cyclotrons, optimum size and spacing of multiple doses of conventional radiation, and, most recently, chemical radiosensitisers. These radiosensitisers mimic the sensitising effect of oxygen and are active only against hypoxic cells. They do not, therefore, increase radiation response in well-oxygenated normal tissues. They are not rapidly metabollised and so can penetrate further than oxygen from the vascular capillaries and effectively reach the hypoxic cells in the tumour. Some of these drugs are of considerable clinical promise. The results of in vitro and in vivo studies with radiosensitisers are summarised and preliminary clinical work is described.

Animals↗
PubMed1976

Skin reaction. A quantitative system for measurement of radiosensitisation in man.

Areas of skin have been irradiated using a radio-strontium plaque giving 800 to 1100 rad. Visual ranking of the reactions produced proved to be the best method of measuring the response. Erythema was poorly related to dose but in most cases the amount of pigmentation produced was directly related to it. This system, for use in the testing of radiosensitisers, allows a quantitative estimate of enhancement of response to be made.

Abdominal Neoplasms↗
PubMed1976

Clinical testing of the radiosensitiser Ro-07-0582. I. Dose tolerance, serum and tumour concentrations.

Patients have been given single oral doses of the radiosensitiser Ro-07-0582 and serum concentrations have been attained in the range expected to be of value in radiosensitisation. Immediate gastrointestinal side effects appear to limit the dose to below 140 mg/kg but radiosensitising serum levels of approximately 200 mug/ml can be attained. Tolerance may be improved by giving anti-emetics and a more palatable preparation. Estimates of the concentration of Ro-07-0582 in tumour have ranged from 12 to 92% of the serum concentration at the time of determination.

Adult↗