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Whelan 1991
Whelan 1991
Summary-Forty patients with multiple recurrent superficial bladder tumours received an 8-week
course of weekly instillations of 4' epirubicin 30 mg in 50 ml saline. The overall response rate was
58%and side effects were minimal.
Among the effective intravesical agents used for resections for recurrent superficial bladder tumours
the treatment of recurrent superficial bladder cancer and 2 patients had previously received 50mg 4'
the anthracyclines (Adriamycin) have been shown epirubicin in 50 ml saline weekly for 2 months.
to be effective both therapeutically (Matsumura et This treatment had ceased 1 month and 5 months
al., 1983) and prophylactically (Niijimaetal., 1983). prior to their entering the study.
Despite their large molecular size and consequent Between March 1986 and December 1988, 40
poor absorption across the bladder wall, these patients (27 males and 13 females) with a mean age
compounds are nonetheless associated with local of 68.8 years (range 39-92) were studied. All had
and systemic side effects (Crawford et al., 1986). been cystoscoped and their pathological grade and
Epirubicin (the 4' epiadriamycin derivative) has stage determined prior to entry (Table 1). Follow-
been reported by Bonfante et al. (1982) to produce up was for a minimum of 12 months.
the same therapeutic response as its parent com- The tumour load was categorised as involving
pound, but with a lower incidence of side effects. more than 50% of the bladder (9 patients), multiple
In our first report on patients receiving 50 mg in but discrete superficial lesions (13), large areas of
50ml saline, this was not the case and 30% of superficial tumour which could be biopsied but not
patients failed to complete the course because of
Table 1 Initial Staging and Grading of Tumour
local and systemic side effects (Cumming et al.,
1990). We have now assessed the response of 40 No. ofpatients
patients to a lower dose of 4' epirubicin (30 mg in
50 ml saline) and also noted the incidence of side TaG 1 10
effects. TaG2 a
TaG3 2
TlGl 6
Patients and Methods T1G2 6
T1G3 1
The study was confined to patients with difficult T2G1 1
and recurrent superficial transitional cell carcinoma T2G2 1
of the bladder. All had received many transurethral Tis 3
600
LOW DOSE INTRAVESICAL EPIRUBICIN IN THE TREATMENTOF SUPERFICIAL BLADDER CANCER 60 1
completely resected (15) or the whole of the bladder Table 3 Response by Pathological Stage and Grade
appearing red and inflamed (3). The response
criteria are shown in Table 2. Complete Good
response response Progression
Base-line samples were taken for full blood count,
platelet estimation, urea and electrolytes and liver TaG 1 3 5 2
function tests. All patients had a chest X-ray and a TaG2 2 2 4
12-lead electrocardiogram prior to entry. TaC3 0 1 1
The patients received an intravesical dose of TlGl 3 1 2
T1G2 1 3 2
30 mg 4 epirubicin in 50 ml normal saline, and this T1C3 0 0 1
was retained for 60min. The instillations were T2G 1 0 0 1
continued weekly for a total of 8 weeks and the T2G2 0 0 1
patients were reviewed for adverse symptoms at Tis 0 0 3
each instillation, with urine being sent for bacteri- Totals 9 12 17
ological examination and blood taken for full blood
count. At weeks 3 and 7, blood was checked for Twelve patients had a good response in that the
urea and electrolytes and also liver function tests. tumour was readily controlled after the course of
In the case of proven urinary tract infection, the treatment by further endoscopic resection; 7 of
appropriate antimicrobial therapy was instituted these patients remained controlled over the 12-
and further instillations were deferred until the month evaluation period but 5 required additional
urine was bacteriologically sterile. Cystoscopy was treatment; in all cases this consisted of further
repeated within 7 days of completion of the course diathermy, although they had developed further
and again approximately 4 weeks after completion. recurrences. The remaining 17 patients showed no
Follow-up continued on a 3-monthly basis there- evidence of response at the first cystoscopy and all
after. subsequently showed evidence of progressive dis-
ease; 2 underwent cystectomy and 4 died during
Results the evaluation period from carcinoma of the
bladder.
Of the 40 patients entered, 2 were not considered
evaluable for treatment response. The first (aged
92) received only 4 instillations at fortnightly
Complications
intervals and was then followed up with urine Complications of intravesical treatment were min-
cytology alone. The second patient complained of imal. One patient had chemical cystitis and treat-
burning 1 week after his first instillation and ment was delayed for 1 week; 8 patients had mild
received no further treatment. Of the remaining 38 degrees of haematuria but all settled on non-specific
patients, 9 were judged to have had a complete measures and in only 1 case was treatment deferred
response at cystoscopy carried out within 4 weeks for 1week. In a total of 248 instillations, there were
of completion of treatment (Table 3). This showed 27 episodes of positive bacterial growth, giving an
no evidence of visible tumour, and biopsies of sites overall infection rate of 10.8%. These and other
where tumour had been present were negative. This complications are shown in Table 4.
complete response was sustained throughout the
12-month evaluation period, although 3 of these
Discussion
patients developed small single superficial recur-
rences which were treated by local diathermy alone. Adriamycin is effective both therapeutically and
prophylactically in the treatment of superficial
Table 2 Response Criteria bladder carcinoma. It has been associated with
troublesome side effects such as chemical cystitis,
Complete response : complete disappearance of tumour cardiotoxicity, alopecia, thrombocytopenia and
confirmed by biopsy marrow suppression. In our previous study (Cum-
Good response : response enabling transurethral resection ming et a/., 1990), using a higher dose of 4’
of residual tumour, with negative epiruhicin (50 mg in 50 ml saline), 32% of patients
biopsies of previously identified tumour failed to complete their course of treatment because
sites
of sidle effects, and 35% of them were judged to
No response: no change in residual tumour area with
additional tumour growth have had at least 1 episode of chemical cystitis
necessitating delay in instillation.
602 BRITISH JOURNAL OF UROLOGY