Gemcitabine versus bacille Calmette‐Guérin after initial bacille Calmette‐Guérin failure in non‐muscle‐invasive bladder cancer

Abstract

BACKGROUND:The efficacy of intravesical gemcitabine was evaluated compared with repeated administration of bacille Calmette-Guérin (BCG) after BCG failure in high-risk, non-muscle-invasive bladder cancer (BC). METHODS: In this multicenter, prospective, randomized, phase 2 trial, eligible patients were those with high-risk non-muscle-invasive BC, failing 1 course of BCG therapy. All patients were randomly allocated to Group A, receiving intravesical gemcitabine (at a dose of 2000 mg/50 mL) twice weekly for 6 consecutive weeks and then weekly for 3 consecutive weeks at 3, 6, and 12 months, or Group B, receiving intravesical BCG (Connaught strain, 81 mg/50 mL) over a 6-week induction course and each week for 3 weeks at 3, 6, and 12 months. Outcome measures were recurrence rate, time to first recurrence, and progression rate. Treatment-related complications were also evaluated. RESULTS: Eighty participants were enrolled, 40 for each group 52.5% in Group A developed disease recurrence versus 87.5% of those in Group B (P ¼ .002). There was no statistically significant difference in mean time to the first recurrence (Group A, 3.9 months; Group B, 3.1 months; P ¼ .09). Kaplan-Meier analysis of 2-year recurrence-free survival showed significant differences between Group A and B (19% and 3%, respectively, P < .008). Seven of 21 (33%) patients in Group A and 13 of 35 (37.5%) patients in Group B had disease progression and underwent radical cystectomy (P ¼ .12). Both intravesical administrations were generally well tolerated. CONCLUSIONS: Gemcitabine might represent a second-line treatment option after BCG failure in high-risk non-muscle-invasive BC patients. Cancer 2010;116:1893-900.

1064 a Novel Simulation Model of Non-Muscle Invasive Bladder Cancer a Platform for a Virtual Randomized Trial of Conservative Therapy vs Cystectomy in BCG Refractory Patients

“…This is lower than in the recent Phase II clinical trial comparing salvage intravesical gemcitabine (33% progression) vs. additional induction BCG (37.5% progression) in patients with recurrent NMIBC despite BCG at 2 years follow-up [11]. The rate of cystectomy was 62% at 5 years which is higher than previously published clinical trials which range from 33% to 56% at a follow-up of 1.5 to 3 years [11][12][13][14][15].…”

“…The study population of 1300 virtual patients is significantly higher than most published series on BCG refractory patients which range from 20-100 patients [11][12][13][14][15]. Our virtual series contained 58% of patients with clinical stage T1 urothelial carcinoma prior to randomization which falls within the range of previous BCG failure trials where 47%-78% had cT1 tumors [11,15]. Thirty-seven percent of patients had cTis prior to the start of the virtual trial which falls within the range of 31%-77% from prior studies [11,15].…”

“…Our virtual series contained 58% of patients with clinical stage T1 urothelial carcinoma prior to randomization which falls within the range of previous BCG failure trials where 47%-78% had cT1 tumors [11,15]. Thirty-seven percent of patients had cTis prior to the start of the virtual trial which falls within the range of 31%-77% from prior studies [11,15].…”

MicroRNA Profile to Predict Gemcitabine Resistance in Bladder Carcinoma Cell Lines

“…Overall recurrence was 25% for gemcitabine-treated patients versus 30% for BCG-treated patients, and progression was equivalent between the groups. Di Lorenzo et al 32 showed that in carcinoma in situ (CIS) patients with BCG failure, gemcitabine treatment resulted in a recurrence rate of 52.5% (v. 87.5% for BCG-treated patients) and a 2-year recurrence-free survival rate of 19% (v. 3% for BCG). There was no improvement in the mean time to first recurrence or disease progression.…”

Alternative therapies in patients with non-muscle invasive bladder cancer

“…On the other hand, Di Lorenzo et al [19] reported a better 2-year recurrence-free survival (3% vs. 19%, p<0.008) with BCG compared to GEM in cases with BCG failure. However this trend was not verified for disease-progression (37.5% vs. 33%, p=0.12) and both groups had similar rates of patients undergoing RC.…”