Adverse Impact of Fibrin Clot Inhibitors on Intravesical Bacillus Calmette-Guerin Therapy for Superficial Bladder Tumors

Abstract

Although intravesical bacillus Calmette-Guerin therapy has proved to be efficacious in the treatment and prophylaxis against tumor recurrence of superficial bladder tumors, its mechanism of action has not been fully elucidated. Previous work has suggested that bacillus Calmette-Guerin organisms attach to the matrix protein, fibronectin, during fibrin clot formation at sites of urothelial disruption and that this attachment was required for the antitumor effect of bacillus Calmette-Guerin to be expressed. Furthermore, drugs inhibiting clot formation were found to abrogate the antitumor effect of intravesical bacillus Calmette-Guerin therapy in a murine bladder tumor model.To examine the effect of inhibitors of fibrin clot formation on the results of intravesical bacillus Calmette-Guerin therapy, a retrospective analysis of 149 evaluable patients receiving intravesical bacillus Calmette-Guerin for superficial bladder tumors was performed. The over-all response rate free of tumor for 29 patients who concomitantly received inhibitors of fibrin clot formation with bacillus Calmette-Guerin therapy was 48%, as compared with 67% for 120 patients who were not receiving these medications (p = 0.0655, chi-square). The most striking difference was noted for patients who failed with recurrent superficial disease. Of the patients who received fibrin clot inhibitors during intravesical bacillus Calmette-Guerin therapy 35% had recurrent superficial tumors compared to only 8% of those who did not receive these drugs during a mean followup of 29.8 plus or minus 11 months (p = 0.005, chi-square). Our study suggests that inhibitors of fibrin clot formation may have an adverse influence on the results of intravesical bacillus Calmette-Guerin therapy for superficial bladder tumors.