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Biomedical subjects

R J Osborne

Publications and source records attributed to R J Osborne.

35 records · Page 2Linked to original sources
PubMed1989

The effect of dose on the bioavailability of oral etoposide: confirmation of a clinically relevant observation.

The effect of dose on the bioavailability of oral etoposide was investigated in ten patients with malignant mesothelioma who received single-agent etoposide as part of a phase II study. Etoposide pharmacokinetics were studied in each patient at oral dose levels of 100, 200, 300, 400 and 600 mg. At doses above 200 mg, the AUC and peak concentrations of etoposide were substantially lower than predictions based on the 100-mg dose. This study confirms previous observations that etoposide absorption is dose-dependent and that a mean bioavailability of approximately 50% cannot be assumed at total oral doses greater than 200 mg.

Administration, Oral↗
PubMed1989

A randomized trial to evaluate the effect of schedule on the activity of etoposide in small-cell lung cancer.

Etoposide is an increasingly used and well-tolerated drug in cancer medicine. Its cytotoxic action is phase-specific and it has demonstrated schedule dependency in both in vitro and animal studies, but clinical evidence of the importance of drug scheduling is uncertain. The two administration schedules of etoposide that have been compared in this randomized study of 39 patients with previously untreated extensive small-cell lung cancer treated with single-agent etoposide were 500 mg/m2 as a continuous intravenous (IV) infusion over 24 hours or five consecutive daily 2-hour infusions each of 100 mg/m2. Both regimens were repeated every 3 weeks, for a maximum of six cycles. Patients received combination chemotherapy with vincristine, doxorubicin, and cyclophosphamide (VAC) or radiotherapy on failure to respond or at relapse, depending on their Karnofsky performance status. The same therapy was used in both arms of the study. All patients are evaluable for response to etoposide. In the 24-hour arm, two patients achieved a partial remission, resulting in an overall response rate of 10%. In the 5-day schedule, 16 patients had a partial response and one had a complete remission, producing an overall response rate of 89%, which was significantly superior to that in the 24-hour arm (P less than .001). The median duration of remission to etoposide in the 5-day arm was 4.5 months. Bone marrow toxicity was similar in both schedules. Etoposide pharmacokinetics were measured in all patients, and total areas under the concentration versus time curves (AUCs) were equivalent in both regimens. This study has clearly demonstrated the importance of etoposide scheduling in humans, and the superiority of five daily infusions over a 24-hour continuous infusion. The response rate to single-agent etoposide using an efficacious schedule in extensive small-cell lung cancer has been determined to be in excess of 80%.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Oral urea in the treatment of secondary tumours in the liver.

Twenty patients with secondary liver tumours, predominantly from colorectal carcinoma, were treated with oral urea at a daily dose of 8 gm-2. Treatment was well tolerated without side-effects. No objective responses were seen. It is concluded that oral urea is ineffective in the treatment of liver metastases from colorectal cancer.

Administration, Oral↗
PubMed1987

Multiple myeloma treated with high dose intravenous melphalan.

High dose melphalan (HDM, 140 mg/m2 i.v.) has been evaluated in 58 patients under 63 years with multiple myeloma. Among previously untreated patients 11/41 (27%) entered a complete remission (CR: no measurable myeloma protein and a normal bone marrow) and 21 (51%) entered a partial remission (more than 50% reduction in myeloma protein and improvement in all other features). Median duration of remission is 19 months. Two patients who had responded to previous conventional treatment entered CR after HDM. Among 15 patients who had failed on previous chemotherapy the response rate was 66% including two CRs. However, in this group all patients have relapsed within 1 year. Profound myelosuppression, moderate nausea, vomiting, mucositis and diarrhoea with reversible alopecia occurred in all patients. There were 10 deaths within 2 months of treatment mainly due to sepsis and haemorrhage. In a subsequent study, high dose methyl prednisolone (1 g/m2 daily for 5 d) has been added to HDM. Response rates are similar with 6/22 (27%) CR, 13/22 (59%) PR and 2/22 NR but there was only one early death, reflecting improvements in medical management. The high CR rate is an encouraging feature of this approach which is now to be the basis of a prospective trial sponsored by the Medical Research Council in which HDM, with and without steroids, is compared to the best available conventional therapy (the MRC VI Myelomatosis trial).

Adult↗
PubMed1986

Morphine intoxication in renal failure: the role of morphine-6-glucuronide.

Patients with impaired renal function may experience severe and prolonged respiratory depression when treated with morphine. This has been attributed to accumulation of the drug during renal failure. Three patients are described who had classical signs of intoxication with morphine in the absence of measurable quantities of morphine in the plasma. The observed clinical effect is attributed to accumulation of the pharmacologically active metabolite morphine-6-glucuronide, which is usually renally excreted. It is concluded that morphine does not accumulate in patients with renal failure but that accumulation of metabolites does occur. The previously reported observations of morphine accumulation during renal failure probably result from the use of radioimmunoassays that cannot distinguish between morphine and morphine-6-glucuronide. Thus the apparent morphine concentration measured with these assays in fact reflects the total quantity of morphine and morphine-6-glucuronide present.

Acute Kidney Injury↗
PubMed1986

A phase II study of tamoxifen in ovarian cancer.

A phase II study of tamoxifen was conducted in 22 patients with stage III and IV ovarian cancer who had failed chemotherapy and who had evaluable disease. Tamoxifen was administered at a dose of 20 mg twice daily continuously until evidence of progression. Twenty-one patients had progression of disease within 3 months and one patient had stable disease for 6 months. There were no objective responses to this treatment.

Adult↗
PubMed1986

A prospective study of 123I-labeled monoclonal antibody imaging in ovarian cancer.

Thirty patients presenting with a pelvic mass were entered into a prospective study on the use of radioimmunoscintigraphy with the 123I-labeled monoclonal antibody HMFG2. The imaging data was obtained without knowledge of the clinical data and compared with subsequent surgical findings. A false-positive diagnosis of ovarian cancer was made in five of ten patients subsequently shown not to have ovarian cancer; thus the technique cannot be used as a screening test. A true-positive diagnosis was made in 19 out of 20 patients shown subsequently to have ovarian cancer. In 18 of these patients the distribution of uptake closely fitted the surgical findings. Methods of improving these results are described. In conclusion, radioimmunoscintigraphy is of no use in determining whether a pelvic mass is due to ovarian cancer, but has benefit in the evaluation of chemotherapy and may, in the future, prevent the need for second-look operations in some circumstances.

Antibodies, Monoclonal↗
PubMed1985

Cardiac arrhythmias during cytotoxic chemotherapy: role of domperidone.

Four patients receiving platinum-containing chemotherapy were treated with domperidone (20 mg) by slow intravenous injection followed by a continuous infusion for 24 h at a dose of 10 mg 24 h-1 kg-1. Cardiac monitoring and plasma potassium and domperidone concentration measurements were performed. Severe cardiac arrhythmias occurred in two patients. A control group of 14 patients treated with similar chemotherapy, without domperidone, also underwent cardiac and plasma potassium monitoring. No significant arrhythmias were seen. The electrophysiologic effects of domperidone are discussed. It is concluded that treatment with intravenous domperidone is associated with the occurrence of cardiac arrhythmias.

Antineoplastic Agents↗
PubMed1981

Endometrial neoplasia--screening the high-risk patient.

Increased longevity and use of exogenous estrogens appear to have placed more women at risk of developing endometrial carcinoma. Too infrequently, a diagnosis is made in these women at the premalignant stage of their disease. We assessed cytologically, by means of the Milan-Markley helix technique, 170 women seen at our institutions. These patients were classified in one of the following groups: late menstruators, periclimacteric bleeders, women receiving hormone replacement therapy, and women with endometrial pathologic conditions at the time of curettage. The diagnostic accuracy of the helix technique was assessed. Histologic confirmation was obtained with either Vabra or formal curettage. Tolerance on the part of the patient was excellent. Discomfort sufficient to terminate the procedure occurred in two of 189 samples. There were no complications. Tissue adequate for diagnosis was obtained in 180 of 189 samples. Sensitivity was 97%, specificity was 96%, and predictive value of a positive result was 97%. No cases of adenocarcinoma failed to be detected. We conclude that the Milan-Markley helix technique is safe and dependable in assessing women at risk of developing uterine pathologic conditions.

Adult↗
PubMedDate not supplied

Who wants second-line, palliative chemotherapy?

This paper reports on a study designed to measure the value attached to second-line, palliative chemotherapy by people with advanced cancer, compared with the value healthy people assume they would attach if they had cancer and to assess reasons for accepting or declining treatment. Subjects comprised 92 people with cancer, 76 healthy control subjects, 60 medical oncologists, 128 clinical oncologists, 72 palliative care physicians, 58 general practitioners and 59 qualified nurses working within oncology. Using a questionnaire presenting two typical but imaginary treatment scenarios, subjects indicated whether treatment would be acceptable to them and, if so, what minimum chance and duration of benefit would make treatment worthwhile. Demographic and social data were also collected. Patients accepted a lower chance of benefit than all other groups. Although the minimum worthwhile duration of benefit was more evenly spread, patients choosing lower time values were over-represented. These results were consistent even when treatment involved greater toxicity. The conclusion drawn from this study is that people with advanced cancer are more willing to accept second-line chemotherapy with a lower chance and shorter duration of benefit than others may imagine. Health care professionals must recognize this when discussing treatment options with patients.

Adult↗