Recommended oral sodium bicarbonate administration for urine alkalinization did not affect the concentration of mitomycin-C in non-muscle invasive bladder cancer patients

Abstract

ObjectiveSodium bicarbonate has been reported to maximize the efficacy of intravesical instillation of mitomycin-C (IVI-MMC) therapy by urine alkalinization in non-muscle-invasive bladder cancer (NMIBC). This study aimed to analyze the changes in MMC concentration according to urinary pH and evaluate the efficacy of sodium bicarbonate to maintain the concentration of active form of MMC during IVI-MMC.MethodsWe prospectively enrolled 26 patients with NMIBC after transurethral resection of bladder tumor. Patients with very high-risk and low-risk NMIBC were excluded. Urinary creatinine, volume, pH, and concentrations of MMC and its degraded form were measured immediately before and after IVI-MMC. The patients were administered 1.5 g of oral sodium bicarbonate during the preceding evening, in the morning, and immediately before the fourth cycle of the six-cycle IVI-MMC. The correlation between MMC concentration and urinary pH changes was explored with or without oral bicarbonate therapy.ResultsRecurrence without progression to muscle-invasive disease was noted in 4 of 26 patients in a 23.7-month follow-up. The mean urinary pH before and after the therapy increased from 6.03 to 6.50, and 6.46 to 7.24, without or with oral SB therapy, respectively. Despite this increase, the concentration of active form of MMC did not change significantly. No correlation was found between urinary pH and MMC concentration. Urine alkalinization by SB administration did not maintain the high concentration of urinary MMC.ConclusionsUrine alkalinization by sodium bicarbonate administration for IVI-MMC did not maintain the high concentration of active urinary MMC in NMIBC.

Establishing an Intravesical Doublet Chemotherapy Clinic for Nonmuscle-Invasive Bladder Cancer Patients

“…If prone to bladder discomfort, nonsteroidal anti-inflammatory drugs, such as ibuprofen or naproxen, may also be taken 1 hour beforehand. 6,7,10,22…”

“…If prone to bladder discomfort, nonsteroidal anti-inflammatory drugs, such as ibuprofen or naproxen, may also be taken 1 hour beforehand. 6,7,10,22 Ordering and Preparing the Drugs. Ordering the drug consists of a proper prescription, preparation of the solution by clinical pharmacist or nurse, delivery of drugs in a timely fashion to the clinic, adequate local storage, and a waste disposal plan.…”

Intravesical mitomycin C (MMC) and MMC + cytosine arabinoside for non‐muscle‐invasive bladder cancer: a randomised clinical trial

“…Additionally, regarding MMC stability in urine, an in vitro study demonstrated that MMC degradation at pH 5.0 (half‐life, 2.8 h) proceeded faster than that at pH 6.0 (half‐life, 12.2 h), and both these degradations were remarkably higher than that at pH 7.0 (half‐life, 38.0 h) [ 15 ]. Furthermore, another in vitro study demonstrated the mean rates of active MMC in buffer solutions of pH 5.0, 6.0, 7.0, and 8.0 as 47.4%, 64.2%, 95.4%, and 100.0%, respectively [ 18 ]. Additionally, this study demonstrated that the 50% inhibitory concentration of cancer cell survival in the buffer of pH ≥6.5 was remarkably lower than that in the buffer of pH <6.0 (e.g.…”

“…Additionally, this study demonstrated that the 50% inhibitory concentration of cancer cell survival in the buffer of pH ≥6.5 was remarkably lower than that in the buffer of pH <6.0 (e.g. 1.33 vs 1.98 μg/mL in T24 cells and 0.92 vs 2.3 μg/mL in 253 J cells) [ 18 ]. Thus, that study suggested that the rate of active MMC is positively associated with urinary pH, and urinary pH of ≥6.5 is speculated to be essential in maintaining the anti‐cancer effects of intravesical MMC therapy.…”

“…In the present study, we focussed on the close association of the pharmacokinetics of intravesical MMC therapy with urinary pH considering that its anti‐cancer effects were remarkably increased after urine alkalisation [ 14 , 15 , 16 ]. In fact, urine alkalisation during intravesical MMC therapy by oral sodium bicarbonate administration was performed to prevent the recurrence and progression of NMIBC [ 17 , 18 ]. However, the administration of sodium bicarbonate is associated with the risk of hypernatraemia [ 19 , 20 ].…”