Efficacy Of Intravesical Chemotherapy Research Articles

Safety and efficacy of intravesical chemotherapy and hyperthermia in the bladder: results of a porcine study

Background Hyperthermia (heating to 43 °C) activates the innate immune system and improves bladder cancer chemosensitivity. Objective To evaluate the tissue penetration and safety of convective hyperthermia combined with intravesical mitomycin C (MMC) pharmacokinetics in live porcine bladder models using the Combat bladder recirculation system (BRS). Methods Forty 60 kg-female swine were anesthetized and catheterized with a 3-way, 16 F catheter. The Combat device was used to heat the bladders to a target temperature of 43 °C with recirculating intravesical MMC at doses of 40, 80, and 120 mg. Dwell-heat time varied from 30–180 min. Rapid necropsy with immediate flash freezing of tissues, blood and urine occurred. MMC concentrations were measured by liquid chromatography tandem-mass spectrometry. Results The Combat BRS system was able to achieve target range temperature (42–44 °C) in 12 mins, and this temperature was maintained as long as the device was running. Two factors increased tissue penetration of MMC in the bladder: drug concentration, and the presence of heat. In the hyperthermia arm, MMC penetration saturated at 80 mg, suggesting that with heating, drug absorption may saturate and not require higher doses to achieve the maximal biological effect. Convective hyperthermia did not increase the MMC concentration in the liver, heart, kidney, spleen, lung, and lymph node tissue even at the 120 mg dose. Conclusions Convective bladder hyperthermia using the Combat BRS device is safe and the temperature can be maintained at 43 °C. Hyperthermia therapy may increase MMC penetration into the bladder wall but does not result in an increase of MMC levels in other organs.

Comparative study of ablative efficacy of intravesical chemotherapy using gemcitabine and mitomycinC with mitomycinC alone for non-muscle invasive bladder carcinoma.

e15538 Background: This comparative study conducted to know the efficacy and safety of intravesical gemcitabine and mitomycinC with mitomycinC alone in refractory bladder cancer. Methods: A total o...

Ablative Intravesical Chemotherapy for Small Recurrent Non-Muscle-Invasive Bladder Cancer: A Prospective Study

Objective: The efficacy of intravesical chemotherapy in abolishing small papillary recurrences of non-muscle-invasive bladder cancer (NMIBC), the disease-free interval in responders and patients' preferences were explored. Methods: When a small (≤1 cm) papillary recurrence of a NMIBC was diagnosed, the patient could choose between immediate transurethral resection of the bladder (TURB) or four weekly intravesical instillations with mitomycin C (MMC) or epirubicin (ERC). Control cystoscopy was scheduled 2-3 weeks after the last instillation. Complete remission was defined as total disappearance of all papillary tumours and negative cytology. Results: 25 patients with 47 recurrence episodes were recruited from February 2003 until August 2011. The median follow-up was 35 months. After exclusion of 2 patients with intolerance to the instillations, 45 study episodes could be analysed. All patients to whom this was proposed preferred the instillations over immediate TURB. Complete, partial and no response was seen in 23 (51%), 6 (13%) and 16 (36%) out of 45 episodes, respectively. The median disease-free interval after complete remission was 16 months (95% confidence interval 9-24). Conclusions: Small papillary recurrences of NMIBC completely disappear in about half of the cases receiving four weekly bladder instillations with MMC or ERC. This is followed by a disease-free interval. Intravesical chemotherapy was preferred by all patients over immediate TURB.

589 BCG-INDUCED DEPLETION OF INTRACELLULAR ATP IN HUMAN UROTHELIAL CARCINOMA CELL LINES CORRELATES WITH CELLULAR INJURY AND CYTOTOXICITY

with the APIMpeptide ATX-101, and thereby attenuating cellular stress responses including DNA repair, a potentiation in the cytostatic effect of both bleomycin and MMC is noted. The absence of tumor also after 41 days suggests complete eradication after a single treatment. Increasing cellular sensitivity to cytostatic agents can potentially increase efficacy of intravesical chemotherapy for NMIBC patients.

Impact of intravesical chemotherapy versus BCG immunotherapy on recurrence of superficial transitional cell carcinoma of the bladder: metaanalytic reevaluation.

Bacille Calmette-Guérin (BCG) immunotherapy is currently considered the most effective agent in the management of superficial bladder cancer. Prior work suggests that the efficacy of intravesical chemotherapy in preventing tumor recurrence may be greater than previously suggested. This latter finding, therefore, brings into question the currently perceived superiority of BCG treatment for this disease. A metaanalysis was performed to rigorously examine existing data relevant to this relationship and to quantify the relative efficacy of both treatment modalities on tumor recurrence. A prospective protocol outlining the above-noted metaanalysis was initially developed followed by a thorough search of the existing published literature using strict eligibility criteria. Nine randomized trials were found that met protocol specifications. These reports contained data on 2,261 patients that were statistically combined using a fixed effects model (Peto). The outcome of interest was the proportion of patients with recurrence at 1, 2, and 3 years following intravesical therapy (i.e., a summary odds ratio, ORp). Combining all nine trials using 1-year recurrence as the endpoint demonstrated significant statistical heterogeneity, although the ORp favored BCG over intravesical chemotherapy (0.89 [0.74-1.07]). This precluded statistical pooling of the data and sensitivity analyses were performed to determine the source of heterogeneity. These tests showed that the prior chemotherapy treatment in a large number of the randomized trials biased study results in favor of the BCG arms. Once the data were stratified on presence or absence of prior drug treatment, intravesical chemotherapy reduced 1-, 2-, and 3-year recurrence by 21% to 82% versus BCG, depending on the endpoint of interest. The available data suggest that clinical trials directly comparing intravesical BCG to intravesical chemotherapy must stratify on the presence or absence of prior chemotherapy. Recurrences following prior intravesical chemotherapy appear less responsive to drug therapy than those in chemotherapy-naive patients. The currently perceived superiority of BCG therapy may therefore be an artifact of this phenomenon, since most randomized trials include chemotherapy failures in their chemotherapy treatment arms.

New Strategy of Bio-Chemoprevention on Recurrence of Superficial Bladder Cancer Based on a Hypothesis of the Mechanism of Recurrence

There are theoretical limits to the efficacy of intravesical chemotherapy for prevention of tumor recurrence after transurethral resection of a superficial bladder cancer. Our multi-institutional studies revealed that the direct efficacy of BCG, intravesical instillation for treatment of an existing tumor is very promising. This efficacy persisted over a long period of time, and the subsequent recurrence rate was markedly reduced. Bladder cancer, sometimes earlier known as an occupational disease, might be related to unknown chemical carcinogens. Since enterobacterias are thought to produce carcinogens and mutagens, including nitroso-compounds in the intestinal tract, BLP (lactobacillus casei preparation), treatment may suppress the production of such compounds by altering the intestinal flora. Preclinical studies have demonstrated that BLP suppresses the development of bladder cancer induced by N-butyl-N-(4-hydroxy-butly)-nitrosamine in mice and rats. A double-blind clinical trial recently revealed that BLP was effective for preventing the recurrence of superficial bladder cancer. Bropirimine, a interferon inducer, is now an internationally developing agent for superficial bladder cancer, which is discussed on the basis of Japanese phase II trial data.