Ondansetron in carcinoid syndrome.
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Biomedical subjects
Publications and source records attributed to H Smedley.
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We have derived sets of human monoclonal antibodies by fusing lymphocytes from cancer patients with a human lymphoid line, LICR-LON/HMy2. Two antibodies, LGL1.1D6 and LLU6.3A4, derived from patients with glioma and bronchial carcinoma respectively, were selected for clinical study on the basis of binding patterns in radioimmunoassays with tumour cell lines and localisation of human tumour xenografts. Highly purified monoclonal antibodies were prepared using bulk supernatants from hybridomas grown in serum free medium. After radiolabelling with 131I, 1 mg antibody was injected intravenously into patients with advanced glioma and carcinoma of the bronchus. Good localisation was obtained in five out of eight patients with glioma and five out of seven patients with carcinoma of the bronchus. Despite the technical difficulties inherent in the production of human monoclonal antibodies this study demonstrates their potential for the clinical localisation of solid tumours.
Twenty-three patients who presented with abdominal pain and were found to have germ cell tumours have been reviewed. The overall survival of these patients was no different from the survival of those presenting with testicular swellings. Intra-abdominal germ cell tumour remains an important differential diagnosis of abdominal pain in men.
One prognostic factor in epithelial ovarian cancer appears to be the patient's age at presentation. We have retrospectively analysed data from 2305 patients with this tumour in East Anglia during the period 1960-1980. The influence of age as a factor in survival was studied by comparing outcome in young patients between the ages of 15 and 35 (3.1% of all cases) with the outcome in the women over 35. The prognosis was significantly better in young patients, even when age correction is applied. This has implications for the management of patients with this common tumour.
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We have investigated the ability of various predictive studies to assess which monoclonal antibody (MCA) will be most useful in the immunoscintigraphic localization of metastatic colorectal carcinoma. A set of MCAs was obtained by fusing splenic lymphocytes from rats immunized with membrane preparations from fresh human colorectal cancer. Supernatants from 17 cloned hybridomas were found to bind strongly to colon carcinoma lines by indirect radioimmunoassay. Immunofluorescence using these MCAs on sections of fresh frozen colon carcinoma and normal tissue revealed different staining patterns. Nine MCAs were purified and labelled with 131I. Groups of mice bearing human colorectal tumour xenografts were given radiolabelled MCA and scanned. Six out of the nine MCAs showed tumour localization as determined by rectilinear scanning. Three MCAs which gave good tumour images in mice were selected for clinical evaluation in patients with advanced colorectal cancer. One gave good tumour images, another targeted to bone marrow and the third bound almost exclusively to normal liver. Clinical evaluation is clearly essential in the selection of MCAs for tumour localization.
Fifteen patients with locally advanced refractory breast cancer have been treated with recombinant leucocyte interferon ( rIFN -alpha A) for up to 12 weeks. Toxicity was considerable with the initial dosage schedule employed but became acceptable after reducing the starting dose by 50%. Minor side effects occurred in all patients and major CNS toxicity in six. Nine patients showed some evidence of tumour regression at 4 weeks. Only two of these were still responding at 12 weeks. Response was unrelated to the length of previous history, oestrogen receptor status or previous responsiveness to cytotoxic or hormone therapy.
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Ten women with advanced locally recurrent breast cancer who had failed to respond to radiation and hormonal and cytotoxic agents were given up to 12 weeks of recombinant leucocyte interferon 20 X 10(6) U/m2 daily or 50 X 10(6) U/m2 three times a week. Within one hour of administration influenza-like symptoms began, which one week later were superseded by lethargy, anorexia, and nausea, with a consequent loss of weight in most patients. Other side effects included profound somnolence, confusion, paraesthesia, and (in one patient) signs of an upper motor neurone lesion in the legs. All these effects together with increased slow wave activity in electroencephalograms from all patients during treatment disappeared when interferon was withdrawn and did not recur on reintroducing the drug at a lower dosage. Studies are continuing to determine the mechanisms of these effects.