INTRAVESICULAR IMMUNOTHERAPY WITH BCG VACCINE AND INTERFERON-αα2B FOR NON-INVASIVE CARCINOMA OF THE URINARY BLADDER: RESULTS OF PROSPECTIVE RANDOMIZED STUDY
https://doi.org/10.17650/1726-9776-2009-5-1-34-39
Abstract
Background: Both bacillus Calmette-Gue’rin (BCG) and interferon-alpha (IFN-α) are active against urinary bladder cancer. In this studywe evaluate the therapeutic efficacy and toxicity of combined intravesical BCG plus IFN-α for treating non-invasive bladder cancer.
Subjects and methods: A total of 149 patients (mean age 63.2 years) were enrolled for the study. The inclusion criteria were histologically verifiednon-invasive transitional cell carcinoma with intermediate and high risks of recurrence and progression. After transurethral tumor resection, all thepatients were randomized in three groups. Group 1 (n=60) was treated with a 6-week course of BCG, 125 mg, starting 14 to 21 days after TUR, Group2 (n=60) patients received 6-week instillations of BCG, 125 mg, plus IFN-α, 6 million units, Group 3 patients (n = 29) had 4-month courses ofintravesical IFN-α, 6 million units, twice daily during 3 consecutive days. A response was assessed by cystoscopy every 3 months after treatment.
Results: A median follow-up of 30.9 months revealed recurrences in 26 (43.3%) patients in the BCG group, 8 (13.3%) patients in the BCG + IFN-αgroup and 18 (62.1%) patients in the IFN-α group. Progression to muscle invasion occurred in 12% and 7% in Groups 1 and 3, respectively, withno progression in Group 2 patients. Three-year relapse-free survival was higher in the BCG+IFN group (78.5% versus 62.6 and 40.2% in theBCG and IFN-α groups, respectively). There was no significant difference between the BCG groups in relapse-free survival. Monotherapy withIFN-α showed a significantly lower response rate than did BCG therapies (p = 0.007). Adverse reactions were observed in 25, 116, and 6.9% ofpatients from Groups 1, 2 and 3, respectively. Toxicity-related withdrawal and treatment delay were similar in both BCG groups. Comparison ofthe rate of adverse reactions revealed a significant difference between the BCG + IFN-α and BCG groups (p = 0.025). The respective rates ofmoderate-to-severe adverse reactions caused by treatment were 6.7 and 21.7% in the BCG+IFN-α and BCG groups, respectively (p = 0.013).
Conclusions: Full-dose intravesical BCG plus IFN-α appears to be much effective than BCG and IFN-α monotherapies despite that there isno significant difference in this study. IFN-α monotherapy showed the lowest complication rate but a lower response rate than those withBCG therapies (p = 0.007). The co-administration of BCG and IFN-α displayed a significantly less complication rate and severe adversereactions (p = 0.025 and p = 0.013, respectively). Longer follow-up is required to validate these findings.
About the Authors
A. A. Minich
N.N. Aleksandrov Republican Research-and-Production Center of Oncology and Medical Radiology, Minsk
Belarus
Belarus
O. G. Sukonko
N.N. Aleksandrov Republican Research-and-Production Center of Oncology and Medical Radiology, Minsk
Belarus
Belarus
A. A. Rolevich
N.N. Aleksandrov Republican Research-and-Production Center of Oncology and Medical Radiology, Minsk
Belarus
Belarus
References
1. Kirkali Z., Chan T., Manoharan M. et al.Bladder cancer: epidemiology, staging andgrading, and diagnosis. Urology2005;66(Suppl 6A):4—34.
2. Матвеев Б.П., Фигурин К.М., Каря-кин О.Б. Рак мочевого пузыря. М.: Вер-дана, 2001.
3. Herr H.W. Tumor progression and sur-vival of patients with high grade, noninva-sive papillary (TaG3) bladder tumors: 15-year outcome. J Urol 2000;163:60—62.
4. Wolf H., Melsen F., Pederson S.E.,Nielson K.T. Natural history of carcinomain situ of the urinary bladder. Scand J UrolNephrol 1994;157:147.
5. Malmstrom P.U., Busch C., Norlen B.J.Recurrence, progression, and survival inbladder cancer: a retrospective analysis of232 patients with greater than or equal to5-year follow-up. Scand J Urol Nephrol1987;21:185—95. 6. Oosterlinck W., Lobel B., Jakse G. et al.Guidelines on bladder cancer. Eur Urol2002;41:105—12.
6. Smith О., Labasky К., Cockett A. et al.Bladder cancer clinical guidelines panelsummary report on the management ofnonmuscle invasive bladder cancer (stagesTa, T1 and Tis). J Urol 1999;162:1697—701.
7. Sylvester R.J., van der Meijden A.P.,Lamm D.L. Intravesical bacillus Calmette-Gue’rin reduces the risk of progression inpatients with superficial bladder cancer: ameta-analysis of the published results ofrandomized clinical trials. J Urol2002;168:1964—70.
8. Bohle A., Jocham D., Bock P.R.Intravesical bacillus Calmette-Guerin ver-sus mitomycin C for superficial bladdercancer: a formal metaanalysis of compara-tive studies on recurrence and toxicity. JUrol 2003;169:90—5.
9. Saint F., Salomon L., Quintela L. et al.Classification, favorising factors, preven-tion and treatment of adverse side-effectsassociated with the Bacillus Calmette-Gu?rin in the treatment of superficial blad-der cancer. Ann Urol 2002;36:120—31.
10. Koya M., Simon M., Soloway M.Complications of intravesical therapy forurothelial cancer of the bladder. J Urol2006;175:2004—10.
11. Belldegrun A., Franklin J., O’Donnell M. et al. Superficial bladdercancer: the role of interferon-alpha. J Urol1998;159:1793—98.
12. Herr H.W., Schwalb D.M., Zhang Z.F.et al. Intravesical bacillus Calmette-Guerintherapy prevents tumor progression anddeath from superficial bladder cancer: ten-year follow-up of a prospective randomizedtrial. J Clin Oncol 1995;13:1404—16.
13. Nseyo U.O., Lamm D.L. Therapy ofsuperficial bladder cancer. Semin Oncol1996;23:598—604.
14. Coplen D.E. Long-term follow-up ofpatients treated with 1 or 2, 6-week coursesof intravesical bacillus Calmette-Guerin:analysis of possible predictors of responsefree of tumor. J Urol 1990;144(3):652—7.
15. Griffiths T.R., Charlton M., Neal D.E.,Powell P.H. Treatment of carcinoma in situwith intravesical Bacillus Calmette-Guerinwithout maintenance. J Urol2002;167:2408—12.
16. Glashan R.W. A randomized controlledstudy of intravesical а-2b interferon in car-cinoma in situ of the bladder. J Urol1990;144:658—61.
17. Torti P.M. Alpha-interferon in superfi-cial bladder cancer: a Northern CaliforniaOncology Group study. J Clin Oncol1988;6:476—83.
18. Chodak G.W. Intravesical interferontreatment of superficial bladder cancer.Urology 1989;34:84—6.
19. Downs T. Pharmacological biocompat-ibility between intravesical preparations ofBCG and interferon-alfa 2b. J Urol1997:158:2311—6.
20. O'Donnell M.A. Experimental andclinical evidence of enhancement of BCGefficacy by adding interferon-alpha. J Urol1997;157:383. Аbstr 1502.
21. Esuvaranthan K., Kamaraj R., Mohan R.S. et al. A phase IIB trial of BCGcombined with interferon alpha for bladdercancer. J Urol 2000;163:152—675 [Abstr].
22. O’Donnell M.A., Krohn J., DeWolf W.C. Salvage intravesical therapywith interferon-α2b plus low dose BacillusCalmette-Guerin is effective in patientswith superficial bladder cancer in whombacillus Calmette-Guerin alone previouslyfailed. J Urol 2001;166:1300—5.
23. O’Donnell M.A., Lilli K., Leopold C.et al. Interim results from a national multi-center phase II trial of combination bacillusCalmette-Guerin plus interferon alfa-2bfor superficial bladder cancer. J Urol2004;172:888—93.
24. Joudi F.N., Smith B.J., O’Donnell M.A. et al. Final results from anational multicenter phase II trial of com-bination bacillus Calmette-Gue’rin plusinterferon alpha-2B for reducing recur-rence of superficial bladder cancer. UrolOncol 2006;24:344—8.
25. O’Donnell M.A., DeWolf W.C.Bacillus Calmette-Guerin immunotherapyfor superficial bladder cancer. Newprospects for an old warhorse. Surg OncolClin N Amer 1995;4:189—92.
26. Keeley F.X. A comparison of the localimmune response to intravesical alpha-interferon and bacillus Calmette-Guerin(BCG) in patients with superficial bladdercancer. J Urol 1994;151:473. Аbstr 983.
27. Borden E.C., Groveman D.S., Nasu T.et al. Antiproliferative activities of interfer-ons against human bladder carcinoma celllines in vitro. J Urol 1984;132:800—4.
28. Fuchsberger N., Kubes M., Kontsek P.et al. In vitro antiproliferative effect ofinterferon alpha in solid tumors: a potentialpredictive test. Neoplasma 1993;40:293—6.
29. Hawkyard S., James K., Prescott S. et al. The effects of recombinant humaninterferon-gamma on a panel of humanbladder cancer cell lines. J Urol1991;145:1078—82.
30. Stricker P., Pryor K., Nicholson T. et al. Bacillus Calmette-Guerin plus intrav-esical in-terferon alpha-2b in patients withsuperficial bladder cancer. Urology1996;48:957—61.
Review
For citations:
Minich A.A., Sukonko O.G., Rolevich A.A. INTRAVESICULAR IMMUNOTHERAPY WITH BCG VACCINE AND INTERFERON-αα2B FOR NON-INVASIVE CARCINOMA OF THE URINARY BLADDER: RESULTS OF PROSPECTIVE RANDOMIZED STUDY. Cancer Urology. 2009;5(1):34-39. (In Russ.) https://doi.org/10.17650/1726-9776-2009-5-1-34-39
Views:
969
Email this article 