The side effects of bacillus calmette-guerin in the treatment of TA Ti bladder cancer do not predict its efficacy: Results from an eortic genito-urinary group phase III trial (original) (raw)
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European Urology, 2003
Objectives: Previous publications have suggested that patients developing local and/or systemic side effects to Bacillus Calmette-Guerin (BCG) have a better clinical result, however it is necessary to determine if toxicity is responsible for improved efficacy. Methods: After transurethral resection, intravesical instillations of BCG were given during a 6-week induction course followed by 3-weekly maintenance courses at 3, 6, 12, 18, 24, 30 and 36 months. The prognostic importance of delaying or stopping BCG due to local and/or systemic side effects was assessed in 487 patients. Results: Patients with local BCG side effects had a significantly longer time to first recurrence, suggesting that side effects are related to efficacy. However patients with a better outcome remain on study for a longer period of time and receive more BCG, thus increasing their risk to develop side effects. To prove whether toxicity is responsible for improved efficacy, the prognostic importance of toxicity occurring prior to the 6 month instillations was assessed using the landmark method. Neither local nor systemic BCG toxicity prior to 6 months was related to subsequent recurrence. Conclusions: While a correlation between BCG toxicity and efficacy exists, this study does not confirm that BCG toxicity is actually responsible for an improved outcome. #
European Urology Supplements, 2003
Objectives: After transurethral resection, the local and systemic side effects of Bacillus Calmette-Guerin (BCG) instillations were assessed during a 6-week induction course followed by 3 weekly maintenance instillations at 3, 6, 12, 18, 24, 30 and 36 months to determine if BCG toxicity increases over time. Methods: 487 patients who received BCG in a multicenter phase III trial were included. Side effects were divided into 5 different treatment periods: the first 6 weeks induction, months 3 and 6, month 12, the second year, and the third year. Results: 99 (20.3%) patients stopped BCG due to side effects. 72 (14.8%) stopped due to local side effects, including 59 for BCG induced cystitis, 33 during the first 6 months. 46 (9.4%) stopped due to systemic side effects: 23 due to fever, 19 within 6 months, and 15 due to general malaise, 12 within 6 months. 68% who stopped due to side effects did so during the first 6 months. The percent stopping after 6 months due to local side effects does not increase and actually decreases for systemic side effects. Conclusions: The majority of local and systemic side effects are seen already during the induction and the first halfyear of maintenance. During further maintenance BCG toxicity does not increase and instillations are generally well tolerated. #
European Urology, 2003
Objectives: After transurethral resection, the local and systemic side effects of Bacillus Calmette-Guerin (BCG) instillations were assessed during a 6-week induction course followed by 3 weekly maintenance instillations at 3, 6, 12, 18, 24, 30 and 36 months to determine if BCG toxicity increases over time. Methods: 487 patients who received BCG in a multicenter phase III trial were included. Side effects were divided into 5 different treatment periods: the first 6 weeks induction, months 3 and 6, month 12, the second year, and the third year. Results: 99 (20.3%) patients stopped BCG due to side effects. 72 (14.8%) stopped due to local side effects, including 59 for BCG induced cystitis, 33 during the first 6 months. 46 (9.4%) stopped due to systemic side effects: 23 due to fever, 19 within 6 months, and 15 due to general malaise, 12 within 6 months. 68% who stopped due to side effects did so during the first 6 months. The percent stopping after 6 months due to local side effects does not increase and actually decreases for systemic side effects. Conclusions: The majority of local and systemic side effects are seen already during the induction and the first halfyear of maintenance. During further maintenance BCG toxicity does not increase and instillations are generally well tolerated. #
2014
AIM To evaluate the effective dose and adverse effects of BCG doses. METHODS We searched published RCTs in Medline and Cochrane database before October 2013. Article using maintenance BCG after TUR in intermediate-high risk non-muscle invasive bladder cancer (NMIBC) and followed for effectiveness, local and systemic side effect are included. Low risk patients, other dose and MIBC were excluded. RESULTS Meta-analysis of 6 clinical trials involving 2719 intermediate-high risk NMIBC patients showed recurrence rate in full dose (81 mg), low dose (27 mg) and very low dose (13.5 mg) were 33.3%, 34.7% and 30%, respectively. Meta-analysis of 2175 patients, 81 mg BCG was found to be superior to 27 mg in reducing tumour recurrences (RR 0.86; 95% CI 0.77-0.96, I2=0% and p=0.008). Meta-analysis of 544 patients, the effectiveness reducing tumour recurrences in 27 mg BCG was found to be superior to 13,5 BCG (RR 0.66; 95% CI 0.49-0.89, I2=8.8% and p=0.006). Systemic side effects were happened in 2...
European Urology, 2013
Background: The optimal dose and duration of intravesical bacillus Calmette-Gué rin (BCG) in the treatment of non-muscle-invasive bladder cancer (NMIBC) are controversial. Objective: To determine if a one-third dose (1/3D) is not inferior to the full dose (FD), if 1 yr of maintenance is not inferior to 3 yr of maintenance, and if 1/3D and 1 yr of maintenance are associated with less toxicity. Design, setting, and participants: After transurethral resection, intermediate-and high-risk NMIBC patients were randomized to one of four BCG groups: 1/3D-1 yr, 1/3D-3 yr, FD-1 yr, and FD-3 yr. Outcome measurements and statistical analysis: The trial was designed as a noninferiority study with the null hypothesis of a 10% decrease in the disease-free rate at 5 yr. Times to events were estimated using cumulative incidence functions and compared using the Cox proportional hazards regression model. Results and limitations: In an intention-to-treat analysis of 1355 patients with a median follow-up of 7.1 yr, there were no significant differences in toxicity between 1/3D and FD. The null hypotheses of inferiority of the disease-free interval for both 1/3D and 1 yr could not be rejected. We found that 1/3D-1 yr is suboptimal compared with FD-3 yr (hazard ratio [HR]: 0.75; 95% confidence interval [CI], 0.59-0.94; p = 0.01). Intermediate-risk patients treated with FD do not benefit from an additional 2 yr of BCG. In high-risk patients, 3 yr is associated with a reduction in recurrence (HR: 1.61; 95% CI, 1.13-2.30; p = 0.009) but only when given at FD. There were no differences in progression or survival. Conclusions: There were no differences in toxicity between 1/3D and FD. Intermediate-risk patients should be treated with FD-1 yr. In high-risk patients, FD-3 yr reduces recurrences as compared with FD-1 yr but not progressions or deaths. The benefit of the two additional years of maintenance should be weighed against its added costs and inconvenience. Trial registration: This study was registered at ClinicalTrials.gov, number NCT00002990;
British Journal of Urological Nursing, 2014
Bladder cancer is the second most common urological cancer in the UK, with over 10 000 cases diagnosed annually. With 80% of urothelial bladder cancers being non-muscle invasive, it is important to understand the treatments available. This review aims to identify and review the literature regarding bacillus Calmette-Guerin (BCG) treatment. An integrative-based review was conducted to generate a broad overview of the existing knowledge for BCG treatment. An open search of online databases was conducted to identify articles published in English from the earliest date available to September 2013, using key terms related to BCG. A significant number of articles were identified. To narrow the results and identify the most relevant articles, the search terms were cross-referenced. The resulting articles were then reviewed using the critical appraisal skills programme framework. The tools provided by CASP give a systematic, transparent and rigorous approach to the quality assessment of research studies. The research articles were then categorized under the following headings: side effects, including local, systemic and age; quality of life; and attrition. The major conclusion from this literature review is that BCG treatment, when given through an induction and maintenance regime, significantly reduces the risk of progression and recurrence. However, there are potential side effects which the patient and the nurse need to be aware. This review also highlighted that there is a lack of research from the UK and that there is a paucity of research showing why patients withdraw from BCG treatment
Purpose: We examined the efficacy of a 12-week prophylactic course of bacillus Calmette-Guerin (BCG) on superficial bladder cancer. Materials and Methods: From August 1992 until July 1994, 70 evaluable patients 41 to 80 years old (mean age 68.5) with high risk transitional cell carcinoma of the bladder were prospectively randomized to a 12-week prophylactic course of BCG (group 2) versus a traditional 6-week course (group 1). Mean followup was 28 months. Results: A 70% tumor-free rate (21 patients) and mean interval of 12.9 months to recurrence were achieved in group 2 compared to 55% (22 patients) and 12.3 months, respectively, in group 1. Group 2 patients had an overall longer disease-free survival, although no statistical significance was achieved. A subgroup of patients with stage Ta cancer in whom at least 1 tumor was resected 12 months before treatment showed the most benefit from long-term prophylactic treatment in terms of disease-free survival. Side effects were only slightly more prominent in group 2, rendering the longer course fairly acceptable. Conclusions: Our findings suggest a difference for better overall results with the 12-week course of BCG. However, a larger number of patients are needed to demonstrate a statistically significant difference between the 2 groups.
Open Journal of Urology, 2015
Objective: The aim of our study was to compare recurrence-free survival between patients who completed treatment with maintenance Bacillus Calmette-Guerin (BCG) and patients who did not complete the planned treatment. Materials and Methods: Data on 115 patients with intermediateand high-risk Non-Muscle Invasive Bladder Cancer (NMIBC) who were treated with BCG were available for analysis. Patients were categorized into 4 groups based on treatment duration: patients who completed three years of maintenance treatment, patients who stopped treatment while on maintenance, patients who were still on-treatment and patients who were treated with induction course only. Results: Of 115 patients, 86 were men and 29 were women with mean age of 67.8 (range 40-93) years. 51% had high-grade tumors and 49% had low-grade tumors. Seventythree patients (63%) had multiple tumors. Thirty patients (26%) were treated with inductiononly, 18 patients (16%) are on-treatment, 14 patients (12%) finished maintenance protocol and 53 patients (46%) discontinued treatment. Reasons for stopping treatment were disease recurrence in 13 patients and toxicity in 40 patients. 5-year recurrence-free survival was 100%, 63%, 60% and 56% in patients who completed maintenance treatment, stopped during maintenance treatment, were on-treatment and those who received induction only therapy, respectively. Conclusions: Patients should be encouraged to adhere to maintenance BCG treatment because of its favorable effect on recurrence-free survival probability.