The authors should be congratulated for their attention to basic and openquestions on intravesical therapy of nonmuscle invasive bladder cancer. Intravesical delivery ofchemotherapy remains partly empirical, and the pharmacokinetics poorly understood. Everyattempt to optimize intravesical therapy should be welcomed. Expensive new strategies todeliver an effective therapeutic tumor dose are currently being explored.1,2 It is reasonable (andmandatory) first to consider and study the basic principles of pharmacokinetics.In this retrospective study Maeda et al investigate the role of pH on the efficacy of intravesicalmitomycin C (MMC) in vivo. Their experience shows that urinary pH higher than 5.5 is associatedwith a decreased risk of tumor recurrence, and they suggest that monitoring urinary pH andurine alkalization may improve the efficacy of mitomycin C intravesical adjuvant treatment.A marked influence of pH solution on the activity of the most commonly used drugs (doxorubicin,epirubicin, MMC and thiotepa) against human transitional cell carcinoma lines has been recognizedfor 30 years.3 MMC and thiotepa show a stronger cytotoxic activity in acid media, and doxorubicinand epirubicin in alkaline media. On the other hand, the instability of MMC in acidic urine is anadditional problem.4 The effectiveness of MMC can probably be enhanced by adjusting solvent andurine pH to the optimum value. Dalton et al found that the recovery of MMC after 2 hours increasedwith increasing urine pH (less than 30% at pH 5 to 5.5 and greater than 80% at pH 6.5 to 8).5 Themost relevant factor accounting for this finding is the nonenzymatic pH dependent degradation ofMMC. To decrease the nonenzymatic degradation, it would be logical to buffer the bladder instillateto pH 7. However, the activity ofMMCis pH dependent and related to its enzymatic activation underacidic pH.6 Therefore, the optimal pH for intravesical MMC should be carefully selected to achieve abalance between nonenzymatic degradation and enzymatic activation.The ideal urinary pH value to achieve the highest activity of MMC has yet to be found.Excessive urine alkalization might be useless or harmful. Although buffered solutions at alkalinepH are commercially available in some countries, tailoring urine pH to the optimum value (whenidentified) by oral sodium bicarbonate would be the best solution. We must also remember thaturinary pH is only one of several factors to consider for optimizing intravesical chemotherapy.
|Number of pages||1|
|Journal||THE JOURNAL OF UROLOGY|
|Publication status||Published - 2011|
All Science Journal Classification (ASJC) codes