Intravesical bacillus Calmette-Guerin versus mitomycin C for superficial bladder cancer: a formal meta-analysis of comparative studies on recurrence and toxicity.
ABSTRACT We compare the therapeutic efficacy and toxicity of intravesical bacillus Calmette-Guerin (BCG) with mitomycin C on recurrence of stages Ta and T1 bladder carcinoma.
Combined published and unpublished data from comparative studies on BCG versus mitomycin C for superficial bladder carcinoma considering possible confounding factors were analyzed. Odds ratio (OR) and its 95% CI were used as primary effect size estimate. Toxicity data were evaluated descriptively.
In 11 eligible clinical trials 1,421 patients were treated with BCG and 1,328 were treated with mitomycin C. Within the overall median followup time of 26 months 38.6% of the patients in the BCG group and 46.4% of those in the mitomycin C group had tumor recurrence. In 7 of 11 studies BCG was significantly superior to mitomycin C, in 3 studies no significant difference was found, while in 1 study mitomycin C was significantly superior to BCG. An overall statistically significant superiority of BCG versus mitomycin C efficacy in reducing tumor recurrence was detected (OR 0.56, 95% CI 0.38 to 0.84, p = 0.005). In the subgroup treated with BCG maintenance all 6 individual studies showed a significant superiority of BCG over mitomycin C (OR 0.43, 95% CI 0.35 to 0.53, p <0.001). In 4 of the 5 studies with reported data on toxicity BCG associated cystitis was significantly more frequent than in the mitomycin C group (53.8% versus 39.2%). The combined cystitis OR was 1.81 (95% CI 1.48 to 2.23, p <0.001). The OR for cystitis in the BCG maintenance group did not significantly differ from that in the nonmaintenance therapy group.
The results suggest superiority of BCG over mitomycin C for prevention of tumor recurrences in the combined data and particularly in the BCG maintenance treatment subgroup, irrespective of the actual (intermediate or high) tumor risk status. The toxicity with BCG is higher but does not differ between BCG maintenance and nonmaintenance groups.
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ABSTRACT: Low-, intermediate- and high-risk categories have been defined to help guide the treatment of patients with NMIBC (Ta, T1, CIS). However, while low- and high-risk disease have been well-classified, the intermediate-risk (IR) category has traditionally comprised a heterogeneous group of patients that do not fit into either of these categories. As a result, many urologists remain uncertain about the categorization of patients as 'intermediate-risk' as well as the selection of the most appropriate therapeutic option for this patient population. To examine current literature and clinical practice guidelines on IR NMIBC and, based on this review, provide urologists with a better understanding of this heterogeneous risk group as well as practical recommendations for the management of IR patients. The IBCG analyzed published clinical trials, meta-analyses and current clinical practice guidelines that examined IR NMIBC available as of September 2013. The definition of IR, patient outcomes and guideline recommendations were considered, as were the limitations of the available literature and additional parameters that may be useful in guiding treatment decisions in IR patients. Currently, definitions and management recommendations for IR NMIBC vary. The most simple and practical definition is that proposed by the IBCG and the AUA: multiple and/or recurrent low-grade Ta tumors. The IBCG proposes that the following factors be considered to aid in clinical decisions in IR disease: number (>1) and size (> 3cm) of tumors, timing (recurrence within 1 year) and frequency (> 1 per year) of recurrences, and previous treatment. In patients without these risk factors, a single, immediate instillation of chemotherapy is advised. In those with 1-2 risk factors, adjuvant intravesical therapy (intravesical chemotherapy or maintenance BCG) is recommended, and previous intravesical therapy should be considered when choosing between these adjuvant therapies. For those with 3-4 risk factors, maintenance BCG is recommended. It is also important that all IR patients are accurately risk stratified both at initial diagnosis and during subsequent follow-up. This requires an appropriate TURBT, vigilance to rule out CIS or other potential high-risk tumors, and review of histological material directly with the pathologist. IR disease is a heterogeneous group and there is paucity of independent studies comparing therapies and outcomes in the subgroups of IR patients. The IBCG has proposed a management algorithm to assist in this regard that considers tumor characteristics, timing and frequency of recurrences and previous treatment. Subgroup analyses of the IR subjects in pivotal EORTC trials and meta-analyses will be important to validate the proposed algorithm and support clear evidence-based recommendations for the subgroups of IR patients.The Journal of urology 03/2014; · 3.75 Impact Factor
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ABSTRACT: To evaluate, for the first time, the mitomycin C (MMC) pharmacokinetics during intravesical hyperthermia treatment based on conductive heat and the stability and recovery of the drug at the end of the instillation period. Eleven patients with recurrent intermediate-risk superficial transitional cell carcinoma of the bladder were treated weekly for six cycles with intravesical MMC (40 mg MMC in 50 ml) in local hyperthermia (45 °C) with Unithermia(®) system. Each instillation lasted 45 min, with the solution being replaced after the first 22 min. The MMC recovery at the end of the two instillation period and the plasmatic pharmacokinetics of MMC were evaluated by high-pressure liquid chromatography. Nine patients completed all the six planned cycles, whereas two patients missed the last cycle because of allergic reactions. No other systemic toxicity was observed, and the local toxicities were mild. Median MMC concentration in the instillation residual solution decreases from the initial 0.8 to 0.22 mg/ml for the 0-22-min instillation period and to 0.38 mg/ml for the 22-45-min instillation period; the median percentage of MMC recovered after instillation was 66.2 and 99.6, respectively. In all patients, MMC plasmatic C max resulted considerably lower than the toxic threshold (400 ng/ml). The MMC is stable during the instillation, and its absorption occurs mainly during the first minutes of the treatment. The plasmatic MMC concentration is always well below the threshold level for myelosuppression, as confirmed by the total lack of hematological toxicity evidenced by the patients. In order to evaluate the efficacy of the treatment performed with UniThermia(®) in reducing the disease recurrence rate in short- and long-term follow-up, we are currently carrying out a clinical multicentric study involving a larger number of patients.Cancer Chemotherapy and Pharmacology 01/2014; · 2.80 Impact Factor
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ABSTRACT: The objective was to conduct a US multicenter, retrospective medical record study examining the effectiveness, safety, and patterns of use of valrubicin for treatment of nonmuscle-invasive bladder cancer (NMIBC) by clinicians since the 2009 reintroduction of valrubicin.Therapeutic Advances in Urology 10/2014; 6(5):181-191.