Fibrin clot inhibitor medication and efficacy of bacillus Calmette-Guerin for bladder urothelial cancer.
OBJECTIVE
Studies suggest that the antitumor effect of bacillus Calmette-Guerin depends on bacillus Calmette-Guerin attachment to fibronectin at fibrin clot formation sites and medications that impact fibrin clot formation may modify bacillus activity. We evaluated the impact of fibrin clot inhibitors on the clinical efficacy of bacillus Calmette-Guerin.


METHODS
We reviewed the records of 907 consecutive patients treated with bacillus Calmette-Guerin between 1990 and 2006. Time to disease recurrence and progression to surgery were compared in patients who did and did not receive fibrin clot inhibitors by Kaplan-Meier methods and multivariate Cox regression models.


RESULTS
Overall 221 patients (24%) received at least 1 fibrin clot inhibitor, including 170, 34 and 52 on aspirin, clopidogrel and warfarin, respectively. Patients on warfarin had shorter time to progression than patients not on warfarin (median 2.1 vs 9.0 years, p <0.005). Patients on aspirin had a significantly improved 5-year probability of freedom from surgery (66% vs 56%, p = 0.029). On multivariate analysis warfarin was associated with an increased risk of progression to surgery (HR 1.89, 95% CI 1.31, 2.74, p = 0.0007), while aspirin was associated with a decreased risk (HR 0.71, 95% CI 0.52, 0.96, p = 0.024). Warfarin alone was associated with an increased risk of tumor recurrence (HR 1.39, 95% CI 1.00, 1.94, p = 0.047).


CONCLUSIONS
These data suggest that the risks of recurrence and progression to surgery after bacillus Calmette-Guerin are higher in patients on warfarin, while the risk of progression is lower in patients on aspirin. These findings may have important treatment implications in patients in whom bacillus Calmette-Guerin is contemplated.
Boorjian
Stephen A
SA
Section of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA. Stephen.Boorjian@fccc.edu
Berglund
Ryan K
RK
Maschino
Alexandra C
AC
Savage
Caroline J
CJ
Herr
Harry W
HW
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D001500:BCG Vaccine / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D000077144:Clopidogrel; D004347:Drug Interactions; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D012189:Retrospective Studies; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D014859:Warfarin / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000925:Anticoagulants; D001500:BCG Vaccine; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D014859:Warfarin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin