Nativ.qxp 25/9/08 9:45 am Page 45
Second-line Treatment for Superficial Bladder Cancer
double- blind study, Portilo et al. compared INF with placebo for T1 TCC have evaluated the value of intravesical chemotherapeutic agents as a
and found no differences in outcome during a mean follow-up time of second-line treatment.
25
In a randomised prospective study,
43 months.
20
In conclusion, INF as a single agent has limited effect, and Malmstrom et al.
26
compared IVT with mitomycin (MMC) versus BCG.
is not suitable for BCG-failure patients. A total of 261 patients with superficial TCC were enrolled in the study.
With a median follow-up of 64 months, a significant disease-free
The combination of a reduced dose of BCG with INF-α2B showed survival benefit in favour of BCG was noted (p=0.04), especially for
encouraging results in several studies. O’Donnell et al.
21
reported an patients with CIS. Cross-over treatment was successful in 39%
initial response rate of 50–60% in patients with recurrent T1 disease of patients with salvage BCG and in only 19% when MMC was used
as second-line treatment. The author concluded that IVT with BCG was
superior to MMC for recurrence prophylaxis. Steinberg et al.
27
assessed
While some patients are not suitable for
the efficacy and safety of intravesical valrubicin for the treatment of
CIS in 90 high-risk patients who relapsed after at least one BCG
anaesthesia and/or radical surgery due
treatment. Each patient received six weekly instillations of valrubicin
to co-morbidities, others refuse to
800mg. Of the 90 patients, 21% had a complete response for at least
six months and only 8% remained disease-free 24 months. Seven
hamper their quality of life and prefer
patients remained disease-free over a median follow-up of 30 months.
to keep the bladder intact. Overall, the recurrence rate was 87% (79 patients), and four patients
died of bladder cancer. The main side effect of valrubicin was
reversible local bladder irritation. In a randomised trial, Lamm et al.
4
following the failure of a single BCG course. Moreover, a final pathology compared IVT BCG with doxorubicin in 262 patients with rapidly
revealed organ-confined disease in a significant number of those who had recurrent Ta, T1, and CIS patients. A clear advantage in favour of BCG
local recurrence and were referred for cystectomy. In a phase II multicentre was demonstrated for Ta, T1 patients (median follow-up 65 months),
study of 467 patients
7
BCG/INF as a second-line treatment resulted in with a probability of 37% for being disease-free at five years
45% disease-free status at a median follow-up time of 24 months. For compared with 17% for those receiving doxorubicine only. For
patients with CIS, this modality showed a high three-year response rate of patients with CIS, the complete response rates were 34 and 70%
54% after a single BCG course, but only 24% complete response rate for the doxorubicin and BCG groups, respectively. Among the patients
after two years following two prior BCG failures.
22
with CIS, the probability of being disease-free at five years was 18%
after treatment with doxorubicin and 45% after BCG therapy.
In conclusion, INF increases the antineoplastic activity of BCG,
especially in resistant and relapsing patients, but not in T1 and CIS In conclusion, second-line conventional IVT chemotherapy is inferior to
refractory disease.
6
a second course of BCG, especially in high-risk (CIS and T1) patients.
Keyhole Limpet Haemocyanin New Chemotherapeutic Agents
Keyhole limpet haemocyanin (KLH) is a non-specific immunomodulator.
The large protein extracted from the sea mollusc Megathura crenulata Gemcitabine
contains many antigenic epitopes, and is considered a strong antigenic Gemcitabine is a novel deoxycytidine analogue with a broad-spectrum
molecule that, it is thought, can modulate cell-mediated and humoral- antitumour activity.
28
Together with cisplatin, it is used as a first-line
immune response. Its efficacy against superficial bladder cancer has been treatment in patients with advanced TCC.
29,30
Dalbagni et al.
28
used
evaluated in several studies. Jurincic-Winkler et al.
23
treated 13 G3 CIS two courses of intravesical gemcitabine twice weekly at a dose of
patients with 20mg of KLH for six weeks, then monthly for one year and
bi-monthly for an additional two years. Only two patients (15.3%) were
Some physicians consider treatment
free of tumour during a follow-up time of 66 and 82 months,
respectively. In a phase I–II trial, Lamm et al.
24
used escalating doses of a failure only after two courses of
weekly KLH IVT given to 64 patients with CIS or Ta, T1 TCC or both. A
intravesical therapy with bacillus
complete response was seen in 50% of patients with CIS, 20% of
patients with residual Ta, T1 TCC and 33% of those with both CIS
Calmette-Guerin, while some consider
and residual Ta, T1 disease. Our own experience with KHL (Halachmi and
it a failure immediately after the
Nativ, unpublished data) included 15 patients with multiple recurrences
(mean 2.41/year) of Ta and T1 TCC who had failed at least one course of
first course.
another IVT. Local recurrence without progression was observed in eight
patients (53.3%) within a mean time of less than one year. All studies 2,000mg/100ml for three consecutive weeks in 30 patients with BCG
reported a low rate of mild side effects. Despite these results and failure. All had intermediate- to high-risk disease, including 23 CIS,
the acceptable safety profile, KHL did not gain enough popularity for the three T1 and four TaG3. Following treatment, 15 patients (50%)
treatment of BCG failures. achieved complete response while 12 had local recurrence within a
median follow-up time of 3.6 months. One of the 15 complete
Conventional Chemotherapeutic Agents responders developed severe urinary toxicity and underwent
It has been shown that BCG antineoplastic activity is superior to cystectomy; the final pathological specimen showed no evidence of
that observed following topical chemotherapy. However, some groups disease. Of the remaining 14, 12 had early recurrence while the other
EUROPEAN UROLOGICAL REVIEW 45