Analyses of the Effects of Intravesical Bacillus Calmette-Guerin (Tokyo 172 Strain) Therapy for Superficial Bladder Cancer

Abstract

In this paper, we summarize the results of a multicentric controlled study of induction treatment with intravesical BCG in patients with superficial bladder cancer (Ta, T1) or CIS. The BCG Tokyo 172 strain (Japan BCG K.K.) was given for 8 weeks, as a rule, in a dose of either 80 mg or 120 mg in 40 ml of saline instilled into the bladder. Sixty-six (90.5%) of the 73 patients registered in the study were evaluable for response. High response rates were obtained in the patients with Ta or T1 tumors, irrespective of the treatment dose; 65.4% CR, 27.3% PR and 7.3% NC for all. The number of CIS patients is too small to draw any conclusions, but 54.5% CR, 36.4% PR and 9.1% NC were obtained. Several factors were evaluated in relation to the tumor ablative effects. The CR rate was significantly higher for tumors less than 1 cm in size compared with tumors 1-3 or larger in size, although the response rates, including CR and PR, were very similar irrespective of the size. Other factors did not contribute to provoke a significant difference. Japanese elder people show a high positive rate of PPD reaction. Thus, in our study, 78% of the patients showed positive PPD reaction. In this situation, no significant relation between PPD reaction and BCG efficacy was obtained. In addition, OKT8, OKT7, OKT4, OKT4/OKT8 ratio, Leu7, ADCC activity and NK activity did not show any correlation with tumor ablative effect of BCG.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term Outcome of a Low-dose Intravesical Bacillus Calmette–Guerin Therapy for Carcinoma In Situ of the Bladder: Results After Six Successive Instillations of 40 mg BCG

“…(20) Despite good clinical efficacy, intravesical BCG instillation raises some serious problems such as frequent occurrence of various adverse effects. Akaza et al (5) observed bladder irritation symptoms in 69%, fever in 43.7% and macroscopic hematuria in 31%. Infrequent but severe adverse effects have also been reported (6), making it necessary to define the optimal BCG instillation method to improve safety while maintaining its efficacy.…”

“…Akaza et al (12) reported that after the treatment of CIS of the bladder with BCG (Tokyo 172 strain) instillation at a dose of 80 mg once weekly for eight consecutive weeks, 27 of the 32 patients (84%) achieved CR. Although the optimal dose of the Tokyo 172 strain had been determined by previous clinical studies (5), we anticipated that it would be possible to reduce the instillation dose, given that the BCG Tokyo 172 strain is more potent [269.91 -28.64 • 10 6 c.f.u. (colony-forming units)/mg] than other strains (13), indicating that equipotent efficacy can be attained even at half of its standard dose (8).…”

“…In Japan, BCG (Tokyo 172 strain) instillation at a dose of 80 mg once weekly for eight consecutive weeks is generally performed (5), but adverse effects related to BCG are major obstacles (6). Many investigations have been conducted using various doses and durations of BCG instillation for improving efficacy and reducing adverse effects (7,8).…”

Bacillus Calmette?Guerin-refractory superficial bladder cancers: focus on pretreatment episodes

“…The dose was selected on the basis of results of extensive studies by Akaza et al [12][13] In some cases treatment was terminated before the course of six instillations could be performed, but all patients received at least three. The patients were asked to refrain, if possible, from urination within 2 h of the instillation and were monitored for bladder irritation, temperature change, and other clinical symptoms.…”

Evolution of drug delivery system from viewpoint of controlled intracellular trafficking and selective tissue targeting toward future nanomedicine

“…In addition to its use as a tuberculosis vaccine, BCG is intravesically infused in non-muscle invasive bladder cancer patients. The therapeutic rate is more than 70% and is significantly higher than that of ICIs [ 118 , 119 ]. However, patients suffer from a high frequency of serious side effects due to the use of the live mycobacterium [ 120 ].…”