Alvaro Morales1, Harry Herr2, Gary Steinberg3, Robert Given4, Zvi Cohen5, John Amrhein6, Ashish M Kamat7. 1. Queen's University, Toronto, Ontario, Canada. 2. Memorial Sloan Kettering Cancer Center, New York, New York. 3. University of Chicago Medical Center, Chicago, Illinois. 4. Urology of Virginia, Virginia Beach, Virginia. 5. Bioniche Therapeutics Corp., Pointe-Claire, Quebec, Canada. 6. Kingston and McDougall Scientific Ltd., Toronto, Ontario, Canada. 7. University of Texas M.D. Anderson Cancer Center, Houston, Texas. Electronic address: akamat@mdanderson.org.
Abstract
PURPOSE: Patients with high risk recurrences after bacillus Calmette-Guérin failure have limited options. We performed an open label study to evaluate the efficacy and safety of intravesical MCNA in this setting. MATERIALS AND METHODS: Patients were treated intravesically with 8 mg MCNA weekly for 6 weeks followed by 3 weekly instillations at months 3, 6, 12, 18 and 24. Cystoscopy and cytology were performed every 3 months for 2 years with mandatory biopsy at 6 months and as clinically indicated thereafter. The primary efficacy end point was the disease-free survival rate at 1 year. RESULTS: A total of 129 patients were enrolled in study, including 91 with carcinoma in situ with or without papillary disease and 38 with papillary only tumors. Most patients had high risk disease. A total of 107 cases were bacillus Calmette-Guérin refractory and 2 or more prior bacillus Calmette-Guérin induction courses had been given in 68. Median followup in all patients was 34.7 months. The overall disease-free survival rate was 25.0% at 1 year and 19.0% at 2 years. In patients with papillary only tumors the disease-free survival rate was 35.1% and 32.2% at 1 and 2 years, respectively. The median disease-free duration in the 30 responders was 32.7 months. The progression-free survival rate was 87.3%, 79.8% and 77.7% at 1, 2 and 3 years, respectively, with a progression event in 28 patients. MCNA was well tolerated and few adverse events led to treatment discontinuation. CONCLUSIONS: Intravesical MCNA achieved significant activity in patients at high risk with nonmuscle invasive bladder cancer in whom bacillus Calmette-Guérin treatment failed, especially those with papillary only tumors and those with bacillus Calmette-Guérin relapse. A durable response was seen, particularly in patients with a response at 1 year. MCNA offers an option for patients who are not candidates for or who refuse cystectomy.
PURPOSE:Patients with high risk recurrences after bacillus Calmette-Guérin failure have limited options. We performed an open label study to evaluate the efficacy and safety of intravesical MCNA in this setting. MATERIALS AND METHODS:Patients were treated intravesically with 8 mg MCNA weekly for 6 weeks followed by 3 weekly instillations at months 3, 6, 12, 18 and 24. Cystoscopy and cytology were performed every 3 months for 2 years with mandatory biopsy at 6 months and as clinically indicated thereafter. The primary efficacy end point was the disease-free survival rate at 1 year. RESULTS: A total of 129 patients were enrolled in study, including 91 with carcinoma in situ with or without papillary disease and 38 with papillary only tumors. Most patients had high risk disease. A total of 107 cases were bacillus Calmette-Guérin refractory and 2 or more prior bacillus Calmette-Guérin induction courses had been given in 68. Median followup in all patients was 34.7 months. The overall disease-free survival rate was 25.0% at 1 year and 19.0% at 2 years. In patients with papillary only tumors the disease-free survival rate was 35.1% and 32.2% at 1 and 2 years, respectively. The median disease-free duration in the 30 responders was 32.7 months. The progression-free survival rate was 87.3%, 79.8% and 77.7% at 1, 2 and 3 years, respectively, with a progression event in 28 patients. MCNA was well tolerated and few adverse events led to treatment discontinuation. CONCLUSIONS: Intravesical MCNA achieved significant activity in patients at high risk with nonmuscle invasive bladder cancer in whom bacillus Calmette-Guérin treatment failed, especially those with papillary only tumors and those with bacillus Calmette-Guérin relapse. A durable response was seen, particularly in patients with a response at 1 year. MCNA offers an option for patients who are not candidates for or who refuse cystectomy.
Authors: Ashish M Kamat; Thomas W Flaig; H Barton Grossman; Badrinath Konety; Donald Lamm; Michael A O'Donnell; Edward Uchio; Jason A Efstathiou; John A Taylor Journal: Nat Rev Urol Date: 2015-03-24 Impact factor: 14.432
Authors: Bimal Bhindi; Ronald Kool; Girish S Kulkarni; D Robert Siemens; Armen G Aprikian; Rodney H Breau; Fadi Brimo; Adrian Fairey; Christopher French; Nawar Hanna; Jonathan I Izawa; Louis Lacombe; Victor McPherson; Ricardo A Rendon; Bobby Shayegan; Alan I So; Alexandre R Zlotta; Peter C Black; Wassim Kassouf Journal: Can Urol Assoc J Date: 2021-08 Impact factor: 1.862
Authors: Roger Li; Debasish Sundi; Jingsong Zhang; Youngchul Kim; Richard J Sylvester; Philippe E Spiess; Michael A Poch; Wade J Sexton; Peter C Black; James M McKiernan; Gary D Steinberg; Ashish M Kamat; Scott M Gilbert Journal: Eur Urol Date: 2020-03-04 Impact factor: 20.096
Authors: Ashish M Kamat; Richard J Sylvester; Andreas Böhle; Joan Palou; Donald L Lamm; Maurizio Brausi; Mark Soloway; Raj Persad; Roger Buckley; Marc Colombel; J Alfred Witjes Journal: J Clin Oncol Date: 2016-01-25 Impact factor: 44.544
Authors: Jelmer H van Puffelen; Samuel T Keating; Egbert Oosterwijk; Antoine G van der Heijden; Mihai G Netea; Leo A B Joosten; Sita H Vermeulen Journal: Nat Rev Urol Date: 2020-07-16 Impact factor: 14.432