Findings merit practice change
Article Type
Changed
Fri, 01/04/2019 - 14:17

 

For patients with suspected low-grade non–muscle-invasive bladder cancer, immediate postresection treatment with intravesicular gemcitabine significantly cut recurrence rates in a double-blind, multicenter, randomized, placebo-controlled trial.

In the intention-to-treat analysis, estimated rates of 4-year recurrence were 35% with gemcitabine and 47% with placebo saline (hazard ratio, 0.66; 95% confidence interval, 0.48-0.90; P less than .001), reported Edward D. Messing of the University of Rochester, New York, and his associates. Gemcitabine also significantly outperformed placebo in the preplanned analysis of patients with confirmed low-grade non–muscle-invasive urothelial cancer (estimated 4-year recurrence rates , 4% and 54% respectively; HR, 0.53; 95% CI, 0.35-0.81; P = .001).

Intravesicular gemcitabine did not significantly reduce all-cause mortality or tumor progression to muscle invasion. “In an underpowered post hoc subgroup analysis, there [also] was no evidence of a benefit of immediate post-TURBT [transurethral resection of bladder tumor] gemcitabine in patients with high-grade non–muscle-invasive urothelial cancer,” the researchers wrote. The report was published May 8 in JAMA.

Robust data already support single-dose intravesicular chemotherapy with mitomycin C or epirubicin immediately after patients undergo TURBT. But in reality, this practice is uncommon in the United States. Meanwhile, systemic gemcitabine already is used to treat bladder cancer, and its intravesicular use appears safe and at least as effective as other chemotherapies, the investigators noted. Therefore, the SWOG S0337 trial enrolled 416 symptomatic patients with suspected low-grade papillary urothelial cancer who received a single intravesicular instillation of either gemcitabine (2 g in 100 mL saline) or saline (100 mL) within 3 hours after transurethral resection of TURBT.

Ten percent of patients did not receive study drug instillation, usually for medical reasons. There were no grade 4-5 adverse events. Grade 3 or lower adverse events did not significantly differ between groups. The study did not capture reliable data on tumor size or treatment at or after recurrence, the researchers said. Taken together, the findings “support using this therapy, but further research is needed to compare gemcitabine with other intravesical agents.”

The National Cancer Institute provided funding. Eli Lilly provided the gemcitabine used in the study. Dr. Messing reported having no relevant conflicts of interest. Three coinvestigators disclosed ties to BioCancell, Incyte, and various other biopharmaceutical companies.

SOURCE: Messing EM et al. JAMA. 2018 May 8;319(18):1880-8.

Body

 

The well designed and executed study “provides important results for patients and physicians alike,” Samuel D. Kaffenberger, MD, David C. Miller, MD, MPH, and Matthew E. Nielsen, MD, MS, wrote in an editorial accompanying the study report in JAMA.

Recurrent bladder cancer exacts major emotional, medical, and monetary costs, the experts stressed. “The natural history of frequent recurrences drives a uniquely intensive and costly program of invasive surveillance and treatment.”

Thus, while the trial results are promising, their “ultimate benefit” will depend on “more consistent and proficient use of intravesical gemcitabine than has been observed for mitomycin,” they said. Disseminating this “simple, safe, effective, and affordable” treatment will require education and mobilization of patients and physicians, advocacy organizations, and health care system leaders.

Dr. Kaffenberger and Dr. Miller are at the University of Michigan, Ann Arbor, and Dr. Nielsen is at the University of North Carolina at Chapel Hill. Dr. Nielsen disclosed stock options via the Grand Rounds Medical Advisory Board. Dr. Miller disclosed ties to Blue Cross Blue Shield of Michigan. Dr. Kaffenberger reported having no conflicts of interest. These comments summarize their editorial (JAMA. 2018 319;18:1864-65).

Publications
Topics
Sections
Body

 

The well designed and executed study “provides important results for patients and physicians alike,” Samuel D. Kaffenberger, MD, David C. Miller, MD, MPH, and Matthew E. Nielsen, MD, MS, wrote in an editorial accompanying the study report in JAMA.

Recurrent bladder cancer exacts major emotional, medical, and monetary costs, the experts stressed. “The natural history of frequent recurrences drives a uniquely intensive and costly program of invasive surveillance and treatment.”

Thus, while the trial results are promising, their “ultimate benefit” will depend on “more consistent and proficient use of intravesical gemcitabine than has been observed for mitomycin,” they said. Disseminating this “simple, safe, effective, and affordable” treatment will require education and mobilization of patients and physicians, advocacy organizations, and health care system leaders.

Dr. Kaffenberger and Dr. Miller are at the University of Michigan, Ann Arbor, and Dr. Nielsen is at the University of North Carolina at Chapel Hill. Dr. Nielsen disclosed stock options via the Grand Rounds Medical Advisory Board. Dr. Miller disclosed ties to Blue Cross Blue Shield of Michigan. Dr. Kaffenberger reported having no conflicts of interest. These comments summarize their editorial (JAMA. 2018 319;18:1864-65).

Body

 

The well designed and executed study “provides important results for patients and physicians alike,” Samuel D. Kaffenberger, MD, David C. Miller, MD, MPH, and Matthew E. Nielsen, MD, MS, wrote in an editorial accompanying the study report in JAMA.

Recurrent bladder cancer exacts major emotional, medical, and monetary costs, the experts stressed. “The natural history of frequent recurrences drives a uniquely intensive and costly program of invasive surveillance and treatment.”

Thus, while the trial results are promising, their “ultimate benefit” will depend on “more consistent and proficient use of intravesical gemcitabine than has been observed for mitomycin,” they said. Disseminating this “simple, safe, effective, and affordable” treatment will require education and mobilization of patients and physicians, advocacy organizations, and health care system leaders.

Dr. Kaffenberger and Dr. Miller are at the University of Michigan, Ann Arbor, and Dr. Nielsen is at the University of North Carolina at Chapel Hill. Dr. Nielsen disclosed stock options via the Grand Rounds Medical Advisory Board. Dr. Miller disclosed ties to Blue Cross Blue Shield of Michigan. Dr. Kaffenberger reported having no conflicts of interest. These comments summarize their editorial (JAMA. 2018 319;18:1864-65).

Title
Findings merit practice change
Findings merit practice change

 

For patients with suspected low-grade non–muscle-invasive bladder cancer, immediate postresection treatment with intravesicular gemcitabine significantly cut recurrence rates in a double-blind, multicenter, randomized, placebo-controlled trial.

In the intention-to-treat analysis, estimated rates of 4-year recurrence were 35% with gemcitabine and 47% with placebo saline (hazard ratio, 0.66; 95% confidence interval, 0.48-0.90; P less than .001), reported Edward D. Messing of the University of Rochester, New York, and his associates. Gemcitabine also significantly outperformed placebo in the preplanned analysis of patients with confirmed low-grade non–muscle-invasive urothelial cancer (estimated 4-year recurrence rates , 4% and 54% respectively; HR, 0.53; 95% CI, 0.35-0.81; P = .001).

Intravesicular gemcitabine did not significantly reduce all-cause mortality or tumor progression to muscle invasion. “In an underpowered post hoc subgroup analysis, there [also] was no evidence of a benefit of immediate post-TURBT [transurethral resection of bladder tumor] gemcitabine in patients with high-grade non–muscle-invasive urothelial cancer,” the researchers wrote. The report was published May 8 in JAMA.

Robust data already support single-dose intravesicular chemotherapy with mitomycin C or epirubicin immediately after patients undergo TURBT. But in reality, this practice is uncommon in the United States. Meanwhile, systemic gemcitabine already is used to treat bladder cancer, and its intravesicular use appears safe and at least as effective as other chemotherapies, the investigators noted. Therefore, the SWOG S0337 trial enrolled 416 symptomatic patients with suspected low-grade papillary urothelial cancer who received a single intravesicular instillation of either gemcitabine (2 g in 100 mL saline) or saline (100 mL) within 3 hours after transurethral resection of TURBT.

Ten percent of patients did not receive study drug instillation, usually for medical reasons. There were no grade 4-5 adverse events. Grade 3 or lower adverse events did not significantly differ between groups. The study did not capture reliable data on tumor size or treatment at or after recurrence, the researchers said. Taken together, the findings “support using this therapy, but further research is needed to compare gemcitabine with other intravesical agents.”

The National Cancer Institute provided funding. Eli Lilly provided the gemcitabine used in the study. Dr. Messing reported having no relevant conflicts of interest. Three coinvestigators disclosed ties to BioCancell, Incyte, and various other biopharmaceutical companies.

SOURCE: Messing EM et al. JAMA. 2018 May 8;319(18):1880-8.

 

For patients with suspected low-grade non–muscle-invasive bladder cancer, immediate postresection treatment with intravesicular gemcitabine significantly cut recurrence rates in a double-blind, multicenter, randomized, placebo-controlled trial.

In the intention-to-treat analysis, estimated rates of 4-year recurrence were 35% with gemcitabine and 47% with placebo saline (hazard ratio, 0.66; 95% confidence interval, 0.48-0.90; P less than .001), reported Edward D. Messing of the University of Rochester, New York, and his associates. Gemcitabine also significantly outperformed placebo in the preplanned analysis of patients with confirmed low-grade non–muscle-invasive urothelial cancer (estimated 4-year recurrence rates , 4% and 54% respectively; HR, 0.53; 95% CI, 0.35-0.81; P = .001).

Intravesicular gemcitabine did not significantly reduce all-cause mortality or tumor progression to muscle invasion. “In an underpowered post hoc subgroup analysis, there [also] was no evidence of a benefit of immediate post-TURBT [transurethral resection of bladder tumor] gemcitabine in patients with high-grade non–muscle-invasive urothelial cancer,” the researchers wrote. The report was published May 8 in JAMA.

Robust data already support single-dose intravesicular chemotherapy with mitomycin C or epirubicin immediately after patients undergo TURBT. But in reality, this practice is uncommon in the United States. Meanwhile, systemic gemcitabine already is used to treat bladder cancer, and its intravesicular use appears safe and at least as effective as other chemotherapies, the investigators noted. Therefore, the SWOG S0337 trial enrolled 416 symptomatic patients with suspected low-grade papillary urothelial cancer who received a single intravesicular instillation of either gemcitabine (2 g in 100 mL saline) or saline (100 mL) within 3 hours after transurethral resection of TURBT.

Ten percent of patients did not receive study drug instillation, usually for medical reasons. There were no grade 4-5 adverse events. Grade 3 or lower adverse events did not significantly differ between groups. The study did not capture reliable data on tumor size or treatment at or after recurrence, the researchers said. Taken together, the findings “support using this therapy, but further research is needed to compare gemcitabine with other intravesical agents.”

The National Cancer Institute provided funding. Eli Lilly provided the gemcitabine used in the study. Dr. Messing reported having no relevant conflicts of interest. Three coinvestigators disclosed ties to BioCancell, Incyte, and various other biopharmaceutical companies.

SOURCE: Messing EM et al. JAMA. 2018 May 8;319(18):1880-8.

Publications
Publications
Topics
Article Type
Click for Credit Status
Ready
Sections
Article Source

FROM JAMA

Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Vitals

 

Key clinical point: Immediate postresection intravesicular gemcitabine significantly reduced the risk of recurrence in patients with suspected low-grade non–muscle-invasive bladder cancer.

Major finding: Estimated rates of 4-year recurrence were 35% with gemcitabine and 47% with placebo (hazard ratio, 0.66; P less than .001).

Study details: Phase 3 multicenter trial of 416 patients randomly assigned to receive gemcitabine (2 g in 100 mL saline) or placebo saline (100 mL) (SWOG S0337).

Disclosures: The National Cancer Institute provided funding. Eli Lilly provided the gemcitabine used in the study. Dr. Messing reported having no relevant conflicts of interest. Three coinvestigators disclosed ties to BioCancell, Incyte, and various other biopharmaceutical companies.

Source: Messing EM et al. JAMA. 2018 May 8;319(18):1880-8.
 

Disqus Comments
Default
Use ProPublica