[speaker001:] .... [cough]
[speaker002:] Chairman and Chairman. Colleagues. That's original at any rate. Erm there are several strains in current use, produced by different manufacturers of B C G, used for the treatment of erm superficial, by which I mean T A, P T A, P T one and in situ disease in the bladder.
[speaker001:] [cough]
[speaker002:] Little is known of the relative efficacy and toxicity of different strains. Therefore in ninety eighty eight the M R C superficial bladder cancer sub-group of the Urological Cancer Working Party set up a study to compare what, at that time, were the commonest strains in use in this country. Er they were the Evans strain, previously Glaxo and the Pasteur strain, made in Paris. And the study was not er designed to include er in situ disease, so we're dealing entirely with P T A and P T one recurrent tumours. There were three objectives in this study, first of all, to measure the response of a marker tumour to the two strains of B C G. Secondly, to measure the incidence of recurrent disease erm while patients were under maintenance therapy, with B G C over a two year period. We decided at that time to follow Brosman's erm regimen which er had had the lowest recurrence rate then reported. And thirdly, to compare adverse events erm er noted with the two strains of B G C. This paper refers to the objectives one and three and the incidence of recurrent disease will be the subject of a later report.... All the patients who were entered into this study were patients with multiple P T A, P T one, erm N X, M naught tumours, then I must stress that they were problem patients. These were patients who either had previously or were being considered for erm intravascular chemotherapy, or even for cystectomy, they were not the patients who may have had one or two recurrences noted at check cystoscopy.... There were the usual exclusion criteria for any erm trial of malignant disease. Before entry into the study, each patient had a cystoscopy and at that time the number and position of tumours within the bladder were noted, the largest tumour was measured in two diameters and was resected into muscle, one tumour was selected as a, a reference tumour and left in situ and all the rest of the tumours were resected. The patient was then randomized to receive either a course of Evans or Pasteur B G C.... The dose was selected to be comparable er, each strain was comparable to the other in terms of dose, B G C was instilled for one hour and then the patient er underwent er weekly installations for six weeks. Three months after entry into the study another cystoscopy was performed, again the number of tumours was counted... and all tumours were, were exsected, if tumours indeed were seen. If the erm marker tumour was present it was measured in two diameters and was resected. If the marker tumour was not seen then the site of the marker tumour was resected. All histological material, both from the first cystoscopy and the second cystoscopy, was sent both to the local pathologist and then representative sections sent to the reference pathologist.... Both groups of patients, those receiving Pasteur and receiving the er... erm Evans B G C, were comparable in terms of sex and age, the category and the grade of the tumour, the number of tumours, the size of the largest tumour, the duration of disease and the size of the marker tumour left in the bladder. I will not bore you with going through a lot of slides showing those comparisons, but in a short paper erm you must take my word for it that the two groups were comparable. Ninety nine patients were entered into this study, two were ineligible, one because of previous malignancy and one because no marker tumour was left in the bladder. That left fifty one to receive Evans B G C and forty six, Pasteur. Three patients, all who happened to be in the Pasteur group were subsequently unavailable. One was lost to follow up before the three month cystoscopy, one died of cardiac failure before their three month cystoscopy and one important patient developed bilateral ureteric obstruction and underwent a cystectomy two months after entry into the study. The histology of the removed bladder showed widespread invasive bladder tumour, not only across the base of the bladder obstructing both ureters but also at other sites in the bladder as well. I put it to you that it is unlikely that such widespread invasive tumour arose from one small marker lesion and the surgeon concerned that this was a staging error initially.... Now, what were the results at the three month cystoscopy? This slide shows erm the findings.... They, you can see that the patients can be considered in four groups, those in the top line which in which the marker tumour was absent and no other tumours were seen in the bladder. The next line, the marker tumour was absent but other tumours were seen in the bladder. There were no examples in line three of patients in which the marker tumour was still present, but no other tumours were seen.... But there were a substantial number of patients in which the marker tumour was present and other tumours were also present. Those results would suggest that the other tumours were in fact new tumours, rather than persistent tumours which had been missed at the first cystoscopy.... Although it er the numbers are small it appears from that as if the response of the marker tumour to Pasteur B G C might be better than to Evans but I can assure that there is no statistical difference in those values. Admittedly, if we had entered five times as many patients there might have been a significant difference but it might have gone either way and we have not been able to show any improvement in response erm to either the Pasteur relative to the Evans or vice versa.... Now, what of the adverse events?... Adverse events were noted a at each installation of B G C and at the time of the first cystoscopy and were scored for severity and the highest score was then re recorded and appears on this erm histogram which relates to frequency as a symptom. Each of the next few slides has the same format.... You will see that there is a very similar distribution of the severity of symptoms of the symptom of frequency in the two groups and that is the case for all the symptoms which were recorded.... For dysuria,... for haematuria, slightly more possibly in the i in the Pasteur group but nothing that reaches statistical significance. Fever and malaise... joint pains and hepatic disfunction.... At the three month cystoscopy, in addition to erm recording the actual tumours in the bladder, the inflammatory response was also recorded and ascribed a score. Er o er ascribed a description of mild, moderate or severe and the degree of inflammatory response was virtually identical in the two groups.... In the slide in which I showed the overall results it appears that about half the patients, the erm marker tumour had been eradicated and in quite a lot of patients there were tumours present. And I must stress that these were all problem patients and if tumours were present they were recorded as so on that previous slide but they were often present in greatly reduced numbers. This shows that in well over eighty percent there were fewer tumours at the three month cystoscopy than there were before the B G C was instilled.... So the conclusions from this M R C study are as follows. First of all, that the marker tumour is eradicated by a six week course of B G C in just over fifty percent of patients and that the number of tumours is reduced in at least eight five percent.
[speaker001:] [cough]
[speaker002:] That in this relatively small study, there was no significant difference in the efficacy or the toxicity of those two strains of B G C.... And thirdly, that it erm demonstrates the usefulness of the marker tumour principle in testing the therapeutic efficacy of agents used in P T A, P T one disease. Thank you.
[speaker001:] [clapping] Thank you. And the paper's now open to discussion. Would you like to come to microphone one please? Er if you do go to microphones three, which is the one at the back, it's rather difficult to see you with the spotlight in my face. If you could wave the programme we're more likely to see you. Microphone one, first. Er from Cairo.