Robert C. F. Leonard
Western General Hospital
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Featured researches published by Robert C. F. Leonard.
BMJ | 1991
J F Smyth; R E Coleman; M Nicolson; W M Gallmeier; Robert C. F. Leonard; M A Cornbleet; S G Allan; B K Upadhyaya; U Bruntsch
OBJECTIVE--To determine the contribution of dexamethasone to the efficacy of the 5-hydroxytryptamine antagonist ondansetron in control of cisplatin induced nausea and vomiting. DESIGN--Randomised double blind crossover study. SETTING--Two cancer centres in teaching hospitals, one in the United Kingdom and the other in Germany. SUBJECTS--100 patients (53 men and 47 women) new to cisplatin chemotherapy, 84 of whom completed two consecutive courses of chemotherapy. INTERVENTIONS--Patients were given intravenous dexamethasone (20 mg) or physiological saline with intravenous ondansetron 8 mg before cisplatin, then ondansetron 1 mg/h for 24 hours. Oral ondansetron 8 mg was taken three times daily on days 2-6. MAIN OUTCOME MEASURES--Incidence of complete or major control of emesis (0-2 episodes in the 24 hours after chemotherapy). RESULTS--Complete or major control was obtained in 49 out of 71 (69%) of patients after receiving ondansetron plus dexamethasone compared with 40 out of 71 (56%) when they were given ondansetron alone (p = 0.012). This effect was most pronounced in the first 12 hours after chemotherapy. Patients receiving the combination also had significantly less nausea. Of the 53 patients who expressed a preference, 38 (72%) preferred the combination treatment (p = 0.002) to ondansetron alone. The effect of ondansetron on delayed emesis was less pronounced. CONCLUSIONS--Dexamethasone makes a significant contribution to the efficacy of ondansetron in the control of acute platinum induced emesis.
Clinical Radiology | 1999
David Collie; John Brush; G A Lammie; Richard Grant; Ian Kunkler; Robert C. F. Leonard; Anna Gregor; Robin Sellar
AIMSnTo assess the range of appearances, and accuracy of various methods of diagnosing leptomeningeal metastases.nnnMATERIALS AND METHODSnIn a retrospective study, the notes and imaging of all patients with a radiological and/or CSF cytological diagnosis of leptomeningeal metastasis (LM) were identified, and assessed for the following: age and sex, primary tumour type, presenting symptoms, initial radiological and cytological diagnosis, radiological appearances and length of survival following diagnosis. Discordance between the CSF cytology and radiological diagnosis of LM was also noted.nnnRESULTSn41 positive cases (36 female) of LM were identified over a 2.7 year period (diagnosis based on: imaging only--19 cases, cytology only--6, both--16 cases). The average age was 48 years, and the most frequent primary tumour was breast carcinoma (27/41). Two thirds of patients presented with at least one cranial or spinal nerve palsy. Where performed, contrast-enhanced CT was normal in 40% (10/25), with LM mistaken for parenchymal disease in a further 24% (6/25). CSF cytology was positive in 85% (22/26). Gadolinium-enhanced MRI was positive in all cases where it was performed (25/25). Pial enhancement and nodularity was the commonest finding (67%), but other manifestations included nodular disease, neural enhancement and white matter changes. Prognosis was uniformly poor.nnnCONCLUSIONnLeptomeningeal metastatic disease has a poor prognosis, and treatment regimen may differ from those of parenchymal CNS metastases. CT is normal or misleading in two thirds of patients, and CSF cytology may also be negative. Gadolinium-enhanced T1-weighted MRI complements CSF cytology, and is the investigation of choice in patients with a non-haematological primary tumour and suspected LM.
Cancer Chemotherapy and Pharmacology | 1999
Sally Clive; Jill Gardiner; Robert C. F. Leonard
Background: Recurrent cutaneous breast cancer is difficult to manage, with surgery, radiotherapy and systemic therapy all having their limitations. Miltefosine is a topical cytostatic agent which may provide an alternative approach in its treatment. Patients and methods: Patients with previously treated progressive cutaneous lesions from breast cancer were treated with miltefosine on a named-patient compassionate supply basis. Miltefosine was applied topically to the skin at a dose of 2 drops/10u2009cm2 skin area. Results: Twenty-five patients were treated, most of whom had been heavily pre-treated. Treatment was continued for a median of 14 weeks (range 2–164). In 7 patients grade I skin toxicities were observed, and in 4 patients grade 3 local toxicities necessitated dose adjustments. A response was seen in 9 patients (1 complete response, 2 partial responses, 6 minor responses) giving a total response rate of 36%, with stable disease in 11 patients (44%) and progressive disease in 5 (20%). Those lesions which were superficial or < 2u2009cm in diameter were most likely to respond. Conclusions: Miltefosine, either used alone or in conjunction with other therapies for distant metastases, is an effective and tolerable local treatment for cutaneous breast cancer.
The Breast | 1998
W.R. Miller; J. Telford; C.D.B. Love; Robert C. F. Leonard; S. Hillier; H. Gundacker; H. Smith; J.M. Dixon
Abstract In situ aromatase activity and endogenous levels of oestrone and oestradiol were measure in breast tumours from 11 postmenopausal women with large primary oestrogen receptor positive breast cancers before and after three months systemic therapy with letrozole (2.5 mg daily). Patients were infused before and after treatment with 3 H androstenedione (20MBq) and 14 C oestrone (1MBq) for 18 hours immediately before surgery. Oestrogens were purified from excised tumours and peripheral plasma. In situ aromatase activity was assessed by determining the relative amounts of 3 H and 14 C in the purified fractions and endogenous oestrone and oestradiol measured by immunoassay. One tumour showed no evidence of in situ oestrogen synthesis both before and after treatment; of the remaining 10 tumours, nine displayed a marked decrease in activity with treatment, the effect being statistically significant ( P = 0.022 by sign test). Endogenous levels of oestrogen (oestradiol + oestrone) also fell with treatment in all 10 tumour pairs examined. These results indicate that systemic therapy with letrozole significantly inhibits in situ oestrogen synthesis and decreases endogenous levels of oestrogen within the breasts of postmenopausal women.
BMJ | 1994
Robert C. F. Leonard; A. Rodger; J.M. Dixon
Few other cancers when they metastasise have such a variable natural course and effect on survival as breast cancer. Patients with hormone sensitive cancers may live for several years without any intervention other than various sequential hormonal manipulations. In contrast, patients with disease that is not hormone sensitive have a much shorter interval free of disease and shorter survival, reflecting the more aggressive biology of hormone independent cancers. The average period of survival after diagnosis of metastatic disease is 18-24 months, but this varies widely between patients.nnClinical patterns of relapse predict future behaviour. Patients with a long interval without disease (more than two years) after primary diagnosis and favourable sites of recurrence (such as local lymph nodes and chest wall) survive longer than patients with either a short interval without disease or recurrence at other sites. Patients with visceral disease have the poorest outlook; these patients tend to have a short interval without disease and have cancers that are biologically more aggressive.nnnnFIG nMedian time of survival associated with sites of metastasis in patients with breast cancer.nnnn#### Hormonal treatment of metastatic breast cancernnPremenopausal womennnPostmenopausal womennnAntioestrogens, aromatase inhibitors, and progestogens may be used in virtually any sequence in responsive patients.nnA patient may present with metastatic breast carcinoma or develop a systemic recurrence after treatment for an apparently localised breast cancer. The aim of treatment is to produce effective control of symptoms with minimal side effects. In terms of drug treatment this ideal is only achieved by hormonal treatment in the 30% of patients whose cancers respond to such drugs. There is …
BMJ | 1986
P S Warrington; S G Allan; M. A. Cornbleet; J. S. Macpherson; J. F. Smyth; Robert C. F. Leonard
Thirty three untreated patients being given cisplatin received metoclopramide (7 mg/kg) for antiemesis by either continuous or intermittent infusion in a random order. Each patient received intravenous dexamethasone in addition. High pressure liquid chromatography was used to measure plasma concentrations of metoclopramide. The two regimens were evaluated for antiemetic efficacy and the incidence of side effects. The intermittent metoclopramide regimen resulted in peak and trough plasma concentrations of metoclopramide with accumulation at eight hours, while the loading dose and continuous infusion resulted in mean plasma concentrations greater than 0.85 micrograms/ml (2.8 mumol/l) throughout the eight hour period. The continuous infusion was associated with a significant improvement in nausea and vomiting and reduction in diarrhoea. Major control of emesis (two episodes or fewer) was achieved in 27 patients receiving continuous metoclopramide compared with 18 receiving intermittent metoclopramide.
European Journal of Cancer | 1990
Simon G. Allan; Moira E. Stewart; Sharon Love; Michael A. Cornbleet; John F. Smyth; Robert C. F. Leonard
Prognostic factors in 411 patients with small cell lung carcinoma have been retrospectively analysed. Univariate analysis of continuous variables showed that prognosis was worse with deteriorating performance status, extensive disease, positive bone scan, increasing age, elevated total white cell count, alkaline phosphatase, lactate dehydrogenase, and decreased serum chloride and albumin. Low serum sodium was less clearly associated with poor survival. Cox multivariate regression showed that performance status, disease extent, age and raised lactate dehydrogenase and white cell count were independent prognostic factors. When disease extent was excluded from analysis, performance status, age, total white cell count, lowered serum chloride and raised lactate dehydrogenase were significant independent prognostic variables.
Cancer Chemotherapy and Pharmacology | 1986
John F. Smyth; Janet S. Macpherson; Pamela S. Warrington; Robert C. F. Leonard; C. Roland Wolf
SummaryThe pharmacological disposition of the anthracenedione mitozantrone has been measured in 11 patients with six different tumour types. Administered at 14 mg/m2 as a 30-min infusion, the drug was assayed by a high-pressure liquid chromatographic technique sensitive to 1 ng mitozantrone/ml plasma. The mean half-lives for mitozantrone in plasma were as follows: α, 9.4 min; β, 1.6 h; γ, 23h. The mean volume of distribution (Vd) was 1565 l. For two patients with impaired liver function the T 1/2 γ and Vd were 63.1 h and 4853 l, respectively. Less than 5% of the administered drug was excreted in urine, but two urinary metabolites were identified. These were not influenced by pre incubation of urine samples with β-glucuronidase or sulphatase, suggesting that neither metabolite is a glucuronide or a sulphate conjugate of mitozantrone. Hepatic metabolism is the major route of elimination of mitozantrone, and caution should be exercised when using this drug for patients with hepatic dysfunction.
Palliative Medicine | 1989
Gerald J. Beattie; Robert C. F. Leonard; John F. Smyth
The incidence and management of bowel obstruction in a series of 105 patients with ovarian adenocarcinoma presenting to this unit were studied retrospectively. Forty-three of these patients developed bowel obstruction during the course of their illness. Patients with more advanced disease at presentation developed obstruction more rapidly. Small bowel obstruction was more common than large bowel obstruction. Surgical intervention at the time of obstruction appeared to produce more favourable responses and longer survival times. Patients treated surgically were less likely to reobstruct. No patient showed any response to chemotherapy given following resolution of the obstruction. Early surgical intervention should be considered in the management of patients with bowel obstruction secondary to ovarian adenocarcinoma.
British Journal of Cancer | 1990
J. N. El-Jabbour; S. S. Akhtar; G. R. Kerr; K. M. Mclaren; John F. Smyth; A. Rodger; Robert C. F. Leonard
Between 1975 and 1984, 125 cases of histologically confirmed soft tissue sarcomata (STS) were registered in the Department of Clinical Oncology in Edinburgh. Of these, 100 were eligible for analysis of prognostic factors. The overall 5-year survival rate was 21.5%. Univariate analysis demonstrated that extent of surgery, radical versus palliative or no radiotherapy, mass as a presenting symptom, metastases at presentation, site, histological type, mitotic activity, grade and UICC stage all had a statistically significant effect on survival. Analysis using the proportional hazard regression model was performed on the 87 patients for whom all variables were recorded. When all histological and clinical features and treatment modalities were included in the model then radiotherapy, surgery, necrosis, sex and mitoses were identified as independent prognostic variables. When symptoms and treatment were excluded then the multivariate analysis identified sex and mitotic activity as independent parameters. For the 33 superficial STS with tumour size recorded multivariate analysis revealed size, necrosis and cellularity as independent prognostic variables. For the 31 deep STS histological type, sex, surgery and radiotherapy were identified as independent prognostic parameters.