The paper from the Spanish CUETO group deals with a multicentre, prospective, randomised
trial comparing intravesical treatment with low-dose bacillus Calmette-Guérin (BCG;
27 mg or one-third dose), very-low-dose BCG (13.5 mg or one-sixth dose), and mitomycin C (MMC; 30 mg) in intermediate-risk patients [
- Ojea A.
- Nogueira J.L.
- Solsona E.
- et al.
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.
]. This trial is a logical continuation of their line of clinical research. In an earlier
study this group compared normal-dose or full-dose BCG (81 mg) with the lower dose of 27 mg and found similar efficacy (recurrences and progression) but lower toxicity (reference
8 from the paper). Importantly, this first study left some doubt as to the efficacy
of the lower dose in high-risk patients. In the current study only intermediate-risk
patients were included, and the lower dose was compared to 30 mg MMC, which probably is the drug of choice in these patients in many countries,
although the dose, for example, in my country is 40 mg! However, looking at the time period this trial was designed and started I can
understand the choice of 30 mg MMC. The third arm is an even lower dose, namely, one sixth of the full dose, 13.5 mg BCG. This study seems sufficiently powered with 430 patients and has a sufficient
follow-up period. Therefore, the outcome seems valid and important. The lowest dose
of BCG has disease-free intervals between those of one-third dose of BCG and MMC,
but it was less than that of one-third dose BCG (not significant). The one-third dose
of BCG was significantly better than MMC, although, again, a rather low dose of MMC
was used. The best results were obtained in primary tumours and with one-third dose
of BCG. So, one-sixth dose of BCG is not as effective as one-third dose of BCG, and
maybe even more importantly, there is no advantage with regard to toxicity, which
is similar in both BCG arms but worse than with MMC. That there are no differences
in progression is not surprising in the light of the low number of events (15 in total).
Therefore, the authors conclude that one-third dose of BCG seems to be the minimum
effective dose for these intermediate-risk patients.