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Biomedical subjects

R Rampling

Publications and source records attributed to R Rampling.

34 records · Page 2Linked to original sources
PubMed1994

Muscle cramping in phase I clinical trials of tirapazamine (SR 4233) with and without radiation.

PURPOSE: Tirapazamine (SR 4233) is a benzotriazine di-N-oxide which acts as a hypoxic cytotoxic agent and as a radiation enhancer when given shortly before or after radiation. Three Phase I clinical trials were designed to determine the maximum tolerated dose, toxicities, pharmacokinetics, and effects on irradiated tumors and normal tissues. METHODS AND MATERIALS: Tirapazamine 9 mg/m2 to 21 mg/m2 was given i.v. 1/2 to 1 h prior to irradiation on a multiple dose schedule of 10 consecutive doses. This was later revised to a three times-per-week schedule for 12 doses. In a second clinical trial, tirapazamine was given in a single dose of 18 mg/m2 to 293 mg/m2 i.v. after irradiation. In a third trial, tirapazamine was administered without irradiation in single doses of 36 mg/m2 to 250 mg/m2, with an option for retreatment. RESULTS: Subjects reported muscle cramping of varying degrees of severity on all three dose schedules. One patient experienced Grade 3 cramping and treatment was discontinued. The most frequent site of cramping were the lower extremities. Creatine phosphokinase (CPK) values were elevated in three patients with associated muscle soreness in one patient. MB (cardiac) isoenzymes were elevated in one patient with no evidence of cardiac muscle damage, and returned to baseline at drug completion. No consistent abnormalities in clinical laboratory values were found. Stretching of the muscle was most effective in relieving the cramping. CONCLUSION: Muscle cramping has been the most frequently reported toxicity in Phase I studies of tirapazamine, though it does not appear to be dose limiting. Dose escalation on the three clinical trials continues. In vitro studies to investigate the cramping are ongoing.

Adult↗
PubMed1994

Peri-tumoural hypoxia in human brain: peroperative measurement of the tissue oxygen tension around malignant brain tumours.

Malignant brain tumours contain focal hypoxic areas that may increase their resistance to chemotherapy and radiotherapy. Following surgical excision, the peri-tumoural area will contain residual viable tumour cells, and this area is therefore the logical site for subsequent therapy. The new bioreductive agents are metabolized under hypoxic conditions to produce a cytotoxic species. Peroperative peri-tumoural micro-polarographic measurements have been made to establish the oxygen environment of this region and to determine whether the hypoxic conditions might allow for bioreductive drug activation. The micro-polarographic method is described and results are presented for "normal" white matter (8 patients) to allow comparison with peri-tumoural brain (8 patients) before and after removal of the tumour. The results suggest that peri-tumoural brain (median pO2 10.8 mmHg, 18% pO2 < 2.5 mmHg) is markedly hypoxic in comparison with the "normal" brain (median pO2 15.3 mmHg, less than 2% < 2.5 mmHg), and that surgery improves peri-tumoural oxygenation towards that of the "normal" white matter. It is concluded that the hypoxic peri-tumoural area can provide the conditions under which bioreductive agents may be activated.

Adult↗
PubMed1994

Does tumour related oedema contribute to the hypoxic fraction of human brain tumours?

Focal hypoxia has been demonstrated and is known to contribute to the resistance of malignant brain tumours to radiation and chemotherapy. Using dynamic needle micro-polarography and tissue morphometry on biopsy specimens, the relationship between the effect of oedema on tissue structure and tissue pO2 was investigated in 24 patients undergoing craniotomy for tumour decompression. An inverse correlation (r = -0.84) was found for intercapillary distance and pO2 levels in peritumoural white matter, but this was less marked (r = -0.22) in tumour, probably as a result of sampling difficulties from tissue heterogeneity. Comparison of maximum pO2 levels in oedematous peritumoural white matter with those in tumour suggests that peritumoural oedema is unlikely to contribute to tumour hypoxia.

Adolescent↗
PubMed1994

rhGM-CSF ameliorates neutropenia in patients with malignant glioma treated with BCNU.

Nitrosoureas are the drugs most effective in the treatment of patients with intracerebral malignant glioma. Their limiting toxicity is delayed myelosuppression. A prospective, randomised crossover study of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was performed in patients receiving BCNU for relapsed glioblastoma, to investigate whether the resulting haematological toxicity profile could be modified by rhGM-CSF. Adequate data for analysis were obtained in 13 patients. Following BCNU, the nadir neutrophil count was higher in 12 out of 13 patients during the rhGM-CSF-protected cycles compared with the unprotected cycles. The median nadir was also significantly higher (1.79, CI 0.76-3.52, P < 0.005). Five episodes of neutropenia (< 2 x 10(9) l-1) occurred during the unprotected cycles compared with none in the rhGM-CSF-protected cycles (P = 0.076). There was no evidence of any effect on platelets. This result shows that the haematological toxicity profile following therapeutic doses of BCNU can be modified. It suggests that rhGM-CSF and other growth factors should be investigated for clinical efficacy in chemotherapy using nitrosoureas.

Adult↗
PubMed1993

A phase II evaluation of human lymphoblastoid interferon (Wellferon) in relapsed high grade malignant glioma. Medical Research Council Brain Tumour Working Party.

During the 1980s a number of studies suggested there might be a role for interferon in the treatment of high grade gliomas. In the light of these reports a formal Phase II evaluation of human lymphoblastoid interferon (Wellferon) was undertaken in patients with high grade gliomas which had relapsed after conventional radiotherapy; 14 patients were treated and no objective clinical responses were seen. This indicates that the overall response rate to interferon therapy in this situation would be less than 20%. It is therefore concluded that interferon administration is unlikely to be of value in the management of relapsed high grade gliomas.

Adult↗
PubMed1992

Phase II study of tauromustine in malignant glioma.

46 eligible patients with either anaplastic astrocytoma (AA) or glioblastoma (GBM) and clinical and computed-tomography-confirmed relapse following primary surgery and radiotherapy received oral tauromustine 130 mg/m2 every 5 weeks. A prospective design allowed for concurrent assessment of both clinical and radiological responses and drug toxicity. 41% of patients improved clinically whilst 46% improved radiologically with 3 complete, 7 partial and 7 minimal responses (WHO criteria). Toxicity included grade III or IV gastrointestinal side-effects (15%), grade III or IV leukopenia (24%) and grade III and IV thrombocytopenia (44%). In 9 clinically responding patients, haematological toxicity led to discontinuation of treatment. All patients were followed-up until death and second-line chemotherapy was not used. Median post-treatment survival was 26 weeks for patients with GBM and 57 weeks for patients with AA. Overall 2-year survival rate was 69% for AA and 23% for GBM. Tauromustine given at the time of relapse has demonstrable antitumour activity in patients not previously treated with chemotherapy.

Adult↗
PubMed1992

Training for clinical oncology: experience in Glasgow 1987-1992.

This paper describes how a joint core training course in clinical oncology was set up at the Beatson Oncology Centre in Glasgow. The course extends over a period of two years and modules are taught in cancer basic sciences, physics and surgical oncology, pathology and natural history of malignant disease, and statistics. The structure and content of the course are described, together with an analysis of the problems encountered. There is an assessment of effectiveness. Proposals are made for a scheme for joint accreditation in oncology.

Cancer Care Facilities↗
PubMed1991

Malignant pineal teratomas: a report on three patients and the case for craniospinal irradiation following chemotherapy.

Malignant pineal teratomas carry a poor prognosis. We describe a long-term survivor after chemotherapy and craniospinal irradiation, and another who achieved only transient disease control with chemotherapy and cranial irradiation. Spinal cord spread occurred in first patient and long-term survivors have been reported following surgery and craniospinal irradiation alone, suggesting a role for craniospinal irradiation following chemotherapy.

Adolescent↗
PubMed1991

Pituitary apoplexy and its effect on vision.

A series of 15 patients with a clinical diagnosis of pituitary apoplexy is reviewed. Clinical features are highlighted, with stress on the defects of visual function and ocular motility, and the associated endocrine abnormalities are described. Potential diagnostic errors and their significance are considered. The incidence of this complication in a large series of pituitary adenoma patients is measured, and the radiological and pathological findings are recorded. The results of treatment by surgery and/or radiotherapy and/or bromocriptine are assessed, particularly in relation to visual consequences, and compared with previous reports in the literature, which are reviewed.

Adult↗
PubMed1987

Fast neutron therapy for soft tissue sarcoma.

Seventy-nine patients with soft tissue sarcoma were treated with fast neutron therapy at the Hammersmith Hospital, MRC Cyclotron Unit. Sixty-six of these, treated between 1971 and 1983 were assessable. The histology was reviewed and graded in 82% of cases and tumors divided into groups according to maximum diameter. In sixteen patients, who were irradiated following complete macroscopic removal of tumor, there was 94% local control and 86% survived 5 years. Of the 50 patients who had gross tumors present 62% were greater than 10 cm in diameter, and 20 were recurrent after previous radiotherapy or surgery or both. Sixty-eight per cent of gross tumors completely regressed and local control was 52%. The main cause of death was metastatic spread, and median survival was 63 months for Grade 1 patients, 9 months for Grade 2, and 7 months for Grade 3. Thus, there was a significant advantage to patients with Grade 1 tumor but little difference between Grades 2 and 3. Twenty-seven patients experienced late complications of treatment, 67% of which involved the skin predominantly and were related to the low energy of neutrons used. Seventeen of the 27 had received previous radiotherapy. Neutron therapy given in this dose and fractionation produced a higher local control rate than photon therapy, but complications were more frequent. Since these mainly involved the skin a lower level of complications may be anticipated using higher energy neutrons which will have a more even distribution of dose and lower skin dosage. Forty-eight per cent of patients developed metastatic disease, indicating the need for effective systemic therapy, especially in Grades 2 and 3 tumors.

Fast Neutrons↗
PubMed1987

Antibody-guided irradiation of advanced ovarian cancer with intraperitoneally administered radiolabeled monoclonal antibodies.

Twenty-four patients with persistent epithelial ovarian cancer after chemotherapy with or without external beam irradiation, were treated with intraperitoneally administered 131I-labeled monoclonal antibodies HMFG1, HMFG2, AUA1, H17E2, directed against tumor-associated antigens. Acute side effects were mild abdominal pain, pyrexia, diarrhea, and moderate reversible pancytopenia. One patient developed a subphrenic abscess requiring surgical drainage. Eight patients with large volume disease, ie, greater than 2 cm tumor diameter, did not respond to antibody-guided irradiation and died of progressive disease within 9 months of treatment. Sixteen patients had small-volume (less than 2 cm) disease at the time of treatment with radiolabeled antibody. Seven patients failed to respond, and of nine initial responders, four patients remain alive and free from disease 6 months to 3 years from treatment. Analysis of the data on relapse indicated that doses greater than 140 mCi were more effective than lower doses. We conclude that the intraperitoneal administration of 140 mCi or more of 131I-labeled tumor-associated monoclonal antibodies represents a new and potentially effective form of therapy for patients with small-volume stage III ovarian cancer.

Antibodies, Monoclonal↗
PubMed1986

Antibody-guided irradiation of malignant pleural and pericardial effusions.

Tumour-associated monoclonal antibodies (HMFG1, HMFG2 and AUA1) radiolabelled with iodine-131 were given intracavitary (intrapleurally and intrapericardially) to patients with malignant effusions. Ten out of 13 effusions (3 pericardial and 7 pleural) responded completely with no fluid reaccumulation between 3 and 18 months. No clinical or other toxicity was observed. This new method of treatment for recurrent malignant effusions is non-toxic and effective resulting in improved quality of life, and, in some cases, prolongation of survival.

Adult↗
PubMed1984

Facial nerve damage in the treatment of tumours of the parotid gland.

The treatment of malignant parotid gland tumours by either surgery or X-radiotherapy alone results in unacceptably high rates of local recurrence. This has led to a combined management, with radiation given either before or after surgery. In the best series this gives an 85% control rate but with severance of the facial nerve in a high proportion of cases. Fast neutron therapy was given for much more advanced tumours and gave the same control rate. Where the facial nerve had been damaged by the tumour, paralysis was lessened substantially in four of nine cases. However neutrons were the apparent course of damage to the nerve in three cases. Two of these had previously received surgery and X-ray therapy.

Adult↗
PubMedDate not supplied

Modern aspects of radiation therapy for glial tumours of the brain.

Radiation was conclusively proved to be of value in the treatment of malignant gliomas in the late 1970's where it enabled an approximate doubling of the survival time. Further study defined a number of prognostic factors which provide a basis for selecting patients for treatment. The introduction of computer tomography (and later magnetic resonance) scanning allowed a more rational approach to target volume definition and a reduction in radiation-related morbidity. Dose-ranging studies defined a standard approach to treatment (60 Gray in 30 fractions). Since then numerous attempts have been made to improve on these results. Marginal benefits have been claimed for altered fractionation schemes, limited volume dose escalation (implants and stereotaxy), radiation sensitisers and particle therapies. However none has become routine in clinical practice. Advances in planning technology have allowed a further reduction in the volume of normal brain irradiated and the potential for dose escalation. Low grade astrocytoma has not been examined in the same way and great doubt exists with respect to optimal treatment. There is a great opportunity for research to realise the potential in the new techniques for improving the outlook for patients with malignant glioma and in clarifying the role of radiation in low grade tumours.

Brain Neoplasms↗