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UROLOGICAL
ONCOLOGY
A
multicentre, randomised prospective trial comparing three intravesical
adjuvant therapies for intermediate-risk superficial bladder cancer: low-dose
bacillus Calmette-Guerin (27 mg) versus very low-dose bacillus Calmette-Guerin
(13.5 mg) versus mitomycin C
Ojea A, Nogueira JL, Solsona E, Flores N, Gómez JM, Molina JR,
Chantada V, Camacho JE, Piñeiro LM, Rodríguez RH, Isorna
S, Blas M, Martínez-Piñeiro JA, Madero R; CUETO Group (Club
Urológico Español De Tratamiento Oncológico)
Complejo Hospitalario Universitario de Vigo, Vigo, Spain
Eur Urol. 2007; 52: 1398-406
- Objective:
The primary aim was to search for lower doses of Bacillus Calmette-Guerin
(BCG) that are effective and have lower toxicity.
- Methods:
A low dose of BCG 27 mg was compared with BCG 13.5mg, using mitomycin
C (MMC) 30 mg as the third arm of comparison. A total of 430 patients
with intermediate-risk superficial bladder cancer were randomised into
three groups. Instillations were repeated once a week for 6 wk followed
by another six instillations given once every 2 wk during 12 wk.
-
Results:
There was a significantly longer disease-free interval for BCG 27 mg
versus MMC 30 mg (p=0.006). There were no statistically significant
differences between BCG 27 mg and BCG 13.5mg (p=0.165) or between BCG
13.5mg and MMC 30 mg (p=0.183). Cox proportional hazards regression
showed that disease-free interval in the multivariate analysis was significantly
better for primary disease and treatment with BCG 27 mg. There were
no significant differences among the three groups with regards to time
to progression and cancer-specific survival time. Local and systemic
toxicity were higher in both BCG treatment groups.
- Conclusions:
One third of the standard dose, BCG 27 mg, seems to be the minimum effective
dose as adjuvant treatment for intermediate-risk superficial bladder
cancer, being more effective than MMC 30 mg. One sixth of the standard
dose, BCG 13.5mg, has the same efficacy as MMC 30 mg but it is more
toxic.
- Editorial
Comment
This trial is based upon precious trials from the CUETO group on low
dose BCG in superficial bladder cancer. Within these non-blinded trials
low dose BCG had shown a reduction in side effects together with equal
efficacy against tumor recurrences. As with most trials, data on progression
suffer from the relatively low numbers of patients in each arm. Furthermore,
the maintenance schedule with BCG was very different from other trials
as a “slow-dose long-term schedule” was applied with 2-weekly
instillations for 6 weeks following the typical 6 weeks induction course.
Still, there are meaningful results to be drawn from this trial, which
are generally important for BCG immunotherapy. BCG immunotherapy is
dose-dependent. One-third (27 mg) of the full dose (81 mg) may be equally
effective, but one-sixth certainly was inferior to one-third. The Kaplan-Meyer
curves still showed superior efficacy of all doses of BCG over MMC.
Dr.
Andreas Bohle
Professor of Urology
HELIOS Agnes Karll Hospital
Bad Schwartau, Germany |