Biomedical subjects
L A Emtage
Publications and source records attributed to L A Emtage.
Phase III randomised study of zoladex versus stilboestrol in the treatment of advanced prostate cancer.
An open randomised Phase III trial was conducted of the depot GnRH analogue goserelin (Zoladex) versus stilboestrol (3 mg/day) in patients with advanced or metastatic prostate cancer. The study included 250 patients and the median follow-up was 43 months. In the Zoladex arm the time to first response was achieved earlier and more patients reported an improvement in symptoms. There was no statistically significant difference between the Zoladex and the stilboestrol arms with regard to survival and time to treatment failure. A major reason for treatment failure was the preponderance of adverse events in patients receiving stilboestrol. It is suggested that stilboestrol should no longer be used for prostate cancer when equally effective alternative treatments are available.
Association between serum albumin and mortality from prostatic cancer.
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Haemostatic changes during hormone manipulation in advanced prostate cancer: a comparison of DES 3 mg/day and goserelin 3.6 mg/month.
Two hundred and fifty patients were entered into a randomized clinical study to compare the effectiveness of goserelin (Zoladex) in depot formulation with diethyl stilboestrol in locally advanced or metastatic prostate cancer. In 22 patients from the two arms of the study regular assessments were made of the effect of these hormone treatments on the haemostatic system. Selection of those patients with no recent surgical intervention and those on no drugs liable to interfere with the haemostatic mechanism was done at entry, in order to remove bias and achieve comparable groups. Baseline comparison of the two treatment groups showed no difference in clinical or biochemical measures of disease extent or activity, including serum prostate specific antigen (PSA) levels. There was a significant fall in plasma antithrombin-III (AT-III) activity in the DES treated group both from baseline and compared with the goserelin group. This effect commenced within 1 month and was maintained until monitoring ceased at 12 months. There was also a significant increase of fibrinolytic activity in the DES treated patients compared with those on goserelin. No divergence between the two treatment groups was seen in any other haematological parameters at baseline or on follow-up. A single AT-III estimation was also performed on a larger group of 74 patients at median follow-up time of 17 months (range 3-24). This confirmed the difference noted in the original study group. In the main study thrombotic episodes were noted in 13/126 patients treated with DES and 0/124 treated with goserelin (P less than 0.001). These findings suggest that lowered AT-III is the major factor through which DES affects the coagulation mechanism, and that no such effect is seen with goserelin treatment despite an equivalent therapeutic efficacy.
Androgen and oestrogen receptor status in benign and neoplastic prostate disease. Study of prevalence and influence on time to progression and survival in prostate cancer treated by hormone manipulation.
TUR chips from 89 men were analysed prospectively for androgen and oestrogen nuclear and cytoplasmic receptors (ANR, ACR, ONR, OCR). Patients were selected on the basis of suspicion of neoplastic change on clinical feel of the prostate. A control group of benign cases was also collected prospectively. Histological examination showed that 46 patients had prostatic carcinoma and 43 had benign prostatic hyperplasia. No difference was found between the 2 groups in terms of prevalence of any of the receptors or in levels of receptor in those who were positive. The patients with neoplastic changes were followed up for a median of 53 months (range 47-64). No significant effect on duration of survival was noted with any of the receptor variables but there was a beneficial association between cytoplasmic oestrogen receptor positivity and progression-free interval. Patients with T category 3 or 4 had a significantly higher chance of being ANR positive than those of lower T category and this may reflect sampling error. There appears to be some evidence to suggest that cytosol oestrogen receptor positivity has a prognostic role in prostate cancer, in terms of time to progression on hormone therapy. Receptor status did not influence survival.
A phase III open randomized study of Zoladex 3.6 mg depot vs. DES 3 mg per day in untreated advanced prostate cancer: a West Midlands Urological Research Group Study.
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Interim report of a randomized trial comparing Zoladex 3.6 mg depot with diethylstilbestrol 3 mg/day in advanced prostate cancer. The West Midlands Urology Research Group.
A study comparing Zoladex 3.6 mg depot with diethylstilbestrol (DES) 3 mg/day was initiated in August 1985. One hundred ninety-three patients with histologically confirmed prostate cancer T3/4 or M1 have been randomized up to 31 March 1987: 95 to Zoladex, 98 to DES. No patient had received prior systemic therapy. There is no bias in the treatment groups in terms of baseline characteristics. Median follow-up is 11 months, and the response rate at 12 months from randomization (CR + PR) for Zoladex is 70 +/- 9.4% and 50 +/- 10.1% for DES. Median time to best response is 6 months for Zoladex and 12 months for DES (using the Kaplan-Meier life table method). Subjective responses are 56 +/- 10.2% for Zoladex and 44 +/- 10% for DES. Five increases in bone pain were found after the first Zoladex treatment, as well as one increased ureteric obstruction. None required treatment withdrawal. Seventeen patients on DES were withdrawn due to adverse reaction (chi 2 = 4.33, 1df, p less than 0.05). Overall survival at 31 March 1987 is 84% for the Zoladex group and 78% for the DES group. This study has shown that Zoladex is superior to DES in achieving early tumor response in advanced prostate cancer, without causing serious complications warranting withdrawal of treatment.
HMFG-2 as a prognostic indicator in superficial bladder cancer.
A series of transitional cell carcinomas and mucosal biopsy specimens of bladder were stained immunohistochemically with the monoclonal antibody HMFG-2. Staining characteristics ranged from luminal staining in well differentiated, superficial lesions to staining of all cells in invasive carcinomas. Invasive tumour nests also stained strongly with the antibody. There was good correlation between the staining pattern and histological assessment of both tumours and mucosal biopsy specimens. Correlation with clinical course showed that it was also a good predictor of subsequent disease progression of superficial tumours. It is suggested that HMFG-2 staining is a sensitive indictor of malignant transformation and that it may have a role as an adjunct to conventional histological examination in the assessment of urothelial carcinomas.
Phase II study of Zoladex depot in advanced prostatic cancer with special reference to criteria of response and survival.
Zoladex is a potent decapeptide analogue of luteinising hormone releasing hormone (LHRH). The drug is formulated as a 3.6 mg depot dispersed in a matrix of d,l-lactide-glycolide copolymer, which is totally biodegradable. This formula releases drug continuously for at least 28 days and reliably suppresses serum testosterone into the castrate range. The effect of the depot was studied in 29 patients with locally advanced or metastatic carcinoma of the prostate. Average age at entry was 71 years (range 52-87) and follow-up was from 13.5 to 34.5 months (median 23). Endocrine studies showed that medical castration was maintained in all cases. Three patients experienced bone pain in the first month of treatment and two others had temporary nephrostomies for worsening ureteric obstruction. Subjective improvement was seen in 23/28 cases (82%). There were no complete responses, but partial response was seen in 24/28 (85.7%) using our own criteria, 24/28 (85.7%) using the criteria recommended by the British Prostate Group (BPG) and 15/28 (53.6%) using NPCP criteria. Stable disease was seen in 3/28 patients (10.7%) by our own or BPG criteria, and in 12/28 patients (42.9%) according to NPCP criteria. Progression of disease was measurable in 21 patients (72.4%) whatever criteria were applied; 11/29 (37.9%) have died, giving a median survival of 10 months (range 2.4-26). Following these encouraging results, a multicentre randomised comparative study with stilboestrol 3 mg daily is being undertaken.
The role of prostate specific antigen in the baseline assessment of patients undergoing hormone therapy for advanced prostate cancer.
One hundred and thirty-nine patients with advanced prostate cancer were entered into a randomised trial to test the efficacy and tolerance of goserelin 3.6 mg depot (Zoladex) versus stilboestrol 3 mg/day. As well as the usual clinical and radiological assessments of extent of disease, we used an immunoradiometric assay of prostate specific antigen (PSA) (Hybritech Europe) and normal laboratory enzymatic assays of acid phosphatase (AP) and alkaline phosphatase (ALKP) for biochemical assessment. The upper limit of normal for PSA was taken as 10 micrograms/l. The range of PSA was wide and differed significantly from that of AP and to a lesser extent ALKP in metastatic cases. PSA outperformed both AP and ALKP in both the local and advanced groups in terms of sensitivity. There was no correlation, however, between histological grade and level of PSA, AP or ALKP (the latter in cases with bone disease). In patients with metastatic disease diagnosed by bone scan, nine patients had one abnormal site/one "hot spot", and all of these had a PSA greater than twice the normal upper limit. Early death due to prostate cancer was noted in four patients with levels of PSA greater than 2500 micrograms/l. PSA is more sensitive than either enzymatic AP or ALKP in both locally advanced and metastatic prostate cancer and is useful in identifying those advanced cases who have single lesions on bone scan. In this series PSA gave an overall sensitivity of 89%, compared with 63% for AP and 64% for ALKP in patients with metastatic disease.
Four primary carcinomas of the large bowel in a young man.
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