© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 8, 597-604,
April 18, 2001
© 2001 Oxford University Press
Methods to Improve Efficacy of Intravesical Mitomycin C: Results of a Randomized Phase III Trial
Affiliations of authors: J. L.-S. Au, R. A. Badalament, M. G. Wientjes, D. C. Young, J. A. Warner, D. L. Pollifrone, Ohio State University, Columbus; P. L. Venema, Leyenburg Teaching Hospital, The Hague, The Netherlands; J. D. Harbrecht, Riverside Methodist Hospital, Columbus, OH; J. L. Chin University of Western Ontario, London, Canada; S. P. Lerner, B. J. Miles, Baylor College of Medicine, Houston, TX.
Correspondence to: Jessie L.-S. Au, Pharm.D., Ph.D., Ohio State University, 496 W. 12th Ave., Columbus, OH 43210 (e-mail: au.1{at}osu.edu).
Background: Intravesical chemotherapy (i.e., placement of the drug directly in the bladder) with mitomycin C is beneficial for patients with superficial bladder cancer who are at high risk of recurrence, but standard therapy is empirically based and patient response rates have been variable, in part because of inadequate drug delivery. We carried out a prospective, two-arm, randomized, multi-institutional phase III trial to test whether enhancing the drug's concentration in urine would improve its efficacy. Methods: Patients with histologically proven transitional cell carcinoma and at high risk for recurrence were eligible for the trial. Patients in the optimized-treatment arm (n = 119) received a 40-mg dose of mitomycin C, pharmacokinetic manipulations to increase drug concentration by decreasing urine volume, and urine alkalinization to stabilize the drug. Patients in the standard-treatment arm (n = 111) received a 20-mg dose without pharmacokinetic manipulations or urine alkalinization. Both treatments were given weekly for 6 weeks. Primary endpoints were recurrence and time to recurrence. Treatment outcome was examined by use of Kaplan–Meier analysis with log-rank tests. Statistical tests were two-sided. Results: Patients in the two arms did not differ in demographics or history of intravesical therapy. Dysuria occurred more frequently in the optimized arm but did not lead to more frequent treatment termination. In an intent-to-treat analysis, patients in the optimized arm showed a longer median time to recurrence (29.1 months; 95% confidence interval [CI] = 14.0 to 44.2 months) and a greater recurrence-free fraction (41.0%; 95% CI = 30.9% to 51.1%) at 5 years than patients in the standard arm (11.8 months; 95% CI = 7.2 to 16.4 months) and 24.6% (95% CI = 14.9% to 34.3%) (P = .005, log-rank test for time to recurrence). Improvements were found in all risk groups defined by tumor stage, grade, focality, and recurrence. Conclusions: This study identified a pharmacologically optimized intravesical mitomycin C treatment with statistically significantly enhanced efficacy.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. A. Hadaschik, H. Adomat, L. Fazli, Y. Fradet, R. J. Andersen, M. E. Gleave, and A. I. So Intravesical Chemotherapy of High-Grade Bladder Cancer with HTI-286, A Synthetic Analogue of the Marine Sponge Product Hemiasterlin Clin. Cancer Res., March 1, 2008; 14(5): 1510 - 1518. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Hu, J. L-S. Au, and M. G. Wientjes Computational Modeling to Predict Effect of Treatment Schedule on Drug Delivery to Prostate in Humans Clin. Cancer Res., February 15, 2007; 13(4): 1278 - 1287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Lu, T.-K. Yeh, M. Tsai, J. L.-S. Au, and M. G. Wientjes Paclitaxel-Loaded Gelatin Nanoparticles for Intravesical Bladder Cancer Therapy Clin. Cancer Res., November 15, 2004; 10(22): 7677 - 7684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Colombo, L. F. Da Pozzo, A. Salonia, P. Rigatti, Z. Leib, J. Baniel, E. Caldarera, and M. Pavone-Macaluso Multicentric Study Comparing Intravesical Chemotherapy Alone and With Local Microwave Hyperthermia for Prophylaxis of Recurrence of Superficial Transitional Cell Carcinoma J. Clin. Oncol., December 1, 2003; 21(23): 4270 - 4276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Lamm Intravesical Therapy for Superficial Bladder Cancer: Slow but Steady Progress J. Clin. Oncol., December 1, 2003; 21(23): 4259 - 4260. [Full Text] [PDF]
|
|
|
|
|
|
A. Giannopoulos, C. Constantinides, E. Fokaeas, C. Stravodimos, M. Giannopoulou, A. Kyroudi, and A. Gounaris The Immunomodulating Effect of Interferon-{gamma} Intravesical Instillations in Preventing Bladder Cancer Recurrence Clin. Cancer Res., November 15, 2003; 9(15): 5550 - 5558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Chen, D. Song, M. G. Wientjes, and J. L-S. Au Effect of Dimethyl Sulfoxide on Bladder Tissue Penetration of Intravesical Paclitaxel Clin. Cancer Res., January 1, 2003; 9(1): 363 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Dalbagni, P. Russo, J. Sheinfeld, M. Mazumdar, W. Tong, F. Rabbani, M. S. Donat, H. W. Herr, P. Sogani, D. dePalma, et al. Phase I Trial of Intravesical Gemcitabine in Bacillus Calmette-Guerin-Refractory Transitional-Cell Carcinoma of the Bladder J. Clin. Oncol., August 1, 2002; 20(15): 3193 - 3198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. Dalton, C. R. Yates, D. Yin, A. Straughn, S. L. Marcus, A. L. Golub, and M. C. Meyer Clinical Pharmacokinetics of 5-Aminolevulinic Acid in Healthy Volunteers and Patients at High Risk for Recurrent Bladder Cancer J. Pharmacol. Exp. Ther., May 1, 2002; 301(2): 507 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Masters Re: Methods to Improve Efficacy of Intravesical Mitomycin C: Results of a Randomized Phase III Trial J Natl Cancer Inst, October 17, 2001; 93(20): 1574 - 1575. [Full Text] [PDF]
|
|
|
|
|
|
J. E. Montie Intravesical Therapy for Bladder Cancer: Empiricism at the Helm J Natl Cancer Inst, April 18, 2001; 93(8): 572 - 573. [Full Text] [PDF]
|
|