The effect of intravesical instillation of antifibrinolytic agents on bacillus Calmette-Guerin treatment of superficial bladder cancer: a pilot study.
OBJECTIVE
We determined whether intravesical instillation of antifibrinolytic agents could improve the antitumor effect of bacillus Calmette-Guerin. We also investigated the impact of these antifibrinolytic agents on the dose of bacillus Calmette-Guerin required for a therapeutic effect.


METHODS
In this randomized, prospective, double-blind, controlled pilot study 257 patients with superficial bladder cancer were randomized into groups A through E. They received 100 to 120 mg intravesical bacillus Calmette-Guerin plus 100 mg para-aminomethylbenzoic acid, 50 to 60 mg bacillus Calmette-Guerin plus 100 mg para-aminomethylbenzoic acid, 100 to 120 mg bacillus Calmette-Guerin plus 2.0 gm epsilon aminocaproic acid, 50 to 60 mg bacillus Calmette-Guerin plus 2.0 gm epsilon aminocaproic acid and 100 to 120 mg bacillus Calmette-Guerin alone, respectively. Prothrombin time and activated partial thromboplastin time of each patient were determined at 2 hours after instillation, and adverse events were evaluated. Tumor recurrence was assessed every 3 months postoperatively by cystoscopy. Median followup was 26.0, 25.0, 24.5, 25.0 and 25.5 months, respectively.


RESULTS
No significant change in prothrombin time or activated partial thromboplastin time was observed, and analysis showed no significant difference in prothrombin time or activated partial thromboplastin time among groups A through E (p = 0.693, 0.756). Recurrence rates at a minimum of median 2 years were 10.6%, 11.1%, 10.0%, 9.3% and 31.8% in groups A through E, respectively. The log rank test showed that recurrence-free probability was statistically different comparing groups A, B, C and D with group E, respectively (p = 0.023, 0.037, 0.031 and 0.020), while pairwise comparisons among groups A, B, C and D showed no significant differences (each p >0.05). The rate of serious adverse events in groups A through E was 9.6%, 3.9%, 15.7%, 5.9% and 13.5%, respectively. However, the differences were not significant (p = 0.222).


CONCLUSIONS
Intravesical instillation of para-aminomethylbenzoic acid or epsilon aminocaproic acid is a more effective and safer method to improve the bacillus Calmette-Guerin antitumor effect, and can reduce the dose of bacillus Calmette-Guerin with the same effect as the full dose.
Pan
Chun-Wu
CW
Department of Urology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shen
Zhou-Jun
ZJ
Ding
Guo-Qing
GQ
D010129:4-Aminobenzoic Acid / Q000008:administration & dosage; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015119:Aminocaproic Acid / Q000008:administration & dosage; D000933:Antifibrinolytic Agents / Q000008:administration & dosage*; D001500:BCG Vaccine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D062366:para-Aminobenzoates
D000276:Adjuvants, Immunologic; D000933:Antifibrinolytic Agents; D001500:BCG Vaccine; D062366:para-Aminobenzoates; C015668:4-aminomethylbenzoic acid; D010129:4-Aminobenzoic Acid; D015119:Aminocaproic Acid