Current strategies for first and second line intravesical therapy for nonmuscle invasive bladder cancer

Hendricksen, Kees; Witjes, J. Alfred

doi:10.1097/mou.0b013e3281c55f2b

Cited by 29 publications

(22 citation statements)

References 41 publications

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“…Today, treatment of nonmuscle invasive bladder cancer (NMIBC) is mainly based on transurethral resection of the bladder (TURB) followed by intravesical instillation of mitomycin-C or bacillus CalmetteGuérin (BCG). 2 However, because NMIBC is mostly multifocal and not readily visible and because the lumen of the bladder is easily accessible by endoscopy, superficial bladder cancer lesions are ideally suited to treatment with photodynamic therapy (PDT). 3,4 This treatment modality involves the administration of a photosensitizer (or a precursor), which is specifically retained by or accumulates to a higher extent in tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Biodistribution and photodynamic effects of polyvinylpyrrolidone-hypericin using multicellular spheroids composed of normal human urothelial and T24 transitional cell carcinoma cells

et al. 2011

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Polyvinylpyrrolidone (PVP)-hypericin is a potent photosensitizer that is used in the urological clinic to photodiagnose with high-sensitivity nonmuscle invasive bladder cancer (NMIBC). We examined the differential accumulation and therapeutic effects of PVP-hypericin using spheroids composed of a human urothelial cell carcinoma cell line (T24) and normal human urothelial (NHU) cells. The in vitro biodistribution was assessed using fluorescence image analysis of 5-μm cryostat sections of spheroids that were incubated with PVP-hypericin. The results show that PVP-hypericin accumulated to a much higher extent in T24 spheroids as compared to NHU spheroids, thereby reproducing the clinical situation. Subsequently, spheroids were exposed to different PDT regimes with a light dose ranging from 0.3 to 18J/cm 2 . When using low fluence rates, only minor differences in cell survival were seen between normal and malignant spheroids. High light fluence rates induced a substantial difference in cell survival between the two spheroid types, killing ∼80% of the cells present in the T24 spheroids. It was concluded that further in vivo experiments are required to fully evaluate the potential of PVP-hypericin as a phototherapeutic for NMIBC, focusing on the combination of the compound with methods that enhance the oxygenation of the urothelium. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

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Section: Introductionmentioning

confidence: 99%

Biodistribution and photodynamic effects of polyvinylpyrrolidone-hypericin using multicellular spheroids composed of normal human urothelial and T24 transitional cell carcinoma cells

et al. 2011

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“…The goal of all these approaches was to improve the penetration and accumulation of drugs in bladder tissues [10][11][12][13]. Intravesical thermo-chemotherapy with mitomycin C (MCC) represents one of the most deeply studied strategies.…”

Section: Introductionmentioning

confidence: 99%

Intravesical thermo-chemotherapy based on conductive heat: a first pharmacokinetic study with Mitomycin C in superficial transitional cell carcinoma patients

Milla

Fiorito

Soria

et al. 2014

Cancer Chemother Pharmacol

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3ABSTRACT Purpose 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. MethodsEleven patients with recurrent intermediate risk superficial transitional cell carcinoma of the bladder were treated weekly for 6 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 (HPLC). ResultsNine patients completed all the 6 planned cycles, whereas 2 patients missed the last cycle because of allergic reactions No other systemic toxicity was observed, the local toxicities were mild. Median MMC concentration in the instillation residual solution decrease from the initial 0.8 mg/ml 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 % 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). ConclusionsThe 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.

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“…Approximately 70% of UCB cases are diagnosed as non-muscle invasive bladder cancer (NMIBC), including stages Ta and T1 [2, 3]. NMIBC is treated by transurethral resection of the bladder tumor (TURBT), followed by the administration of adjuvant intravesical treatment with bacillus Calmette-Guerin (BCG) or chemotherapeutic agents, such as adriamycin (ADM), mitomycin C (MMC), gemcitabine (GEM), or docetaxel (DTX) [4, 5]. These intravesical treatments can decrease recurrence rates and prolong the progression-free interval [6, 7].…”

Section: Introductionmentioning

confidence: 99%

Topical and systemic immunoreaction triggered by intravesical chemotherapy in an N-butyl-N-(4-hydroxybutyl) nitorosamine induced bladder cancer mouse model

et al. 2017

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Intravesical bacillus Calmette-Guerin (BCG) treatment is the most common therapy to prevent progression and recurrence of non-muscle invasive bladder cancer (NMIBC). Although the immunoreaction elicited by BCG treatment is well documented, those induced by intravesical treatment with chemotherapeutic agents are much less known. We investigated the immunological profiles caused by mitomycin C, gemcitabine, adriamycin and docetaxel in the N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced orthotopic bladder cancer mouse model. Ninety mice bearing orthotopic bladder cancer induced by BBN were randomly divided into six groups and treated with chemotherapeutic agents once a week for four weeks. After last treatment, bladder and serum samples were analyzed for cell surface and immunological markers (CD4, CD8, CD56, CD204, Foxp3, and PD-L1) using immunohistochemistry staining. Serum and urine cytokine levels were evaluated by ELISA. All chemotherapeutic agents presented anti-tumor properties similar to those of BCG. These included changes in immune cells that resulted in fewer M2 macrophages and regulatory T cells around tumors. This result was compatible with those in human samples. Intravesical chemotherapy also induced systemic changes in cytokines, especially urinary interleukin (IL)-17A and granulocyte colony stimulating factor (G-CSF), as well as in the distribution of blood neutrophils, lymphocytes, and monocytes. Our findings suggest that intravesical treatment with mitomycin C and adriamycin suppresses protumoral immunity while enhancing anti-tumor immunity, possibly through the action of specific cytokines. A better understanding of the immunoreaction induced by chemotherapeutic agents can lead to improved outcomes and fewer side effects in intravesical chemotherapy against NMIBC.

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Current strategies for first and second line intravesical therapy for nonmuscle invasive bladder cancer

Cited by 29 publications

References 41 publications

Biodistribution and photodynamic effects of polyvinylpyrrolidone-hypericin using multicellular spheroids composed of normal human urothelial and T24 transitional cell carcinoma cells

Biodistribution and photodynamic effects of polyvinylpyrrolidone-hypericin using multicellular spheroids composed of normal human urothelial and T24 transitional cell carcinoma cells

Intravesical thermo-chemotherapy based on conductive heat: a first pharmacokinetic study with Mitomycin C in superficial transitional cell carcinoma patients

Topical and systemic immunoreaction triggered by intravesical chemotherapy in an N-butyl-N-(4-hydroxybutyl) nitorosamine induced bladder cancer mouse model

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