Pharmacodynamics and pharmacokinetics of intravesical mitomycin C upon different dwelling times

Abstract

The schedule in dosing of intravesical chemotherapy has thus far received little attention. Correlation of optimal contact time with bladder toxicity, as well as maximal chemotherapeutic effect for one of the drugs of first choice for intravesical instillation, i.e. mitomycin C (MMC), is a particularly important question. In a randomized study, we treated bladder cancer patients with intravesical MMC using 30-min and 60-min dwelling times. There were 28 evaluable patients in each of the 2 groups. The groups were comparable with respect to mean age, sex ratio and distribution of primary or recurrent and single or multiple tumors. Stages and grades of tumors were also comparable over both treatment groups. Pharmacokinetics of MMC and degradation/metabolism were monitored during the first 4 cycles and the last (8th) cycle using HPLC and mass spectrometry. Recurrence was significantly lower in the 60-min treatment group (35.7% vs. 14.3%, chi 2 test; 0.01 less than p less than 0.05). No recurrences were found in patients with Ta and T1 tumors when the 60-min dwelling time was used. Toxicity was mild and transient; the incidence was, surprisingly, lower in the 60-min group but the difference failed to reach the level of significance. Pharmacokinetics of systemic MMC and recovery in the urine was comparable over both groups and systemic absorption was calculated to be in the range of 1-5%.

O comportamento clínico e histológico da pele do rato submetida ao uso tópico e injetável de Mitomicina C

“…É comumente usada como quimioterápico, em aplicações endovenosas, para tratamento de corioepitelioma, sarcoma de células reticulares, seminoma e tumores epiteliais, além de tumores da cavidade bucal, pulmões, intestino, pâncre-as e estômago. Também, em alguns casos, é usada em tratamento anti-neoplásico por contato, principalmente em tumores da bexiga 1,2,3 . Como efeitos colaterais graves, notou-se aplasias medulares em doses endovenosas acima de 50mg e necroses teciduais locais quando do extravasamento da droga no subcutâneo.…”

Intravesical α-Radioimmunotherapy with 213Bi-Anti-EGFR-mAb Defeats Human Bladder Carcinoma in Xenografted Nude Mice

“…In general, mitomycin C is known for its necrotizing properties, resulting also in severe complications in the kidneys such as ureteral inflammation and stenosis (24). Studies on intravesical instillation of mitomycin C revealed a transurothelial resorption of 1%25% of mitomycin C due to its molecular weight of 334 Da (25,26). Moreover, in vitro studies of pharmacodynamics of mitomycin C on surgical bladder tumor samples have documented heterogeneity in the response of bladder tumors (27).…”

Intensive Intravesical Mitomycin C Therapy in Non-Muscle-Invasive Bladder Cancer: A Dose Intensity Approach

“…A randomized study comparing 30-60 min dwelling time of MMC showed a lower recurrences rate in the 60-min treatment group [15] . In other studies, Au et al [11] focalized the methods to improve the efficacy of intravesical MMC.…”