The Clinical Effectiveness and Safety of Intravesical Mitomycin-C and Gemcitabine Sequential Therapy

Phase 2 clinical, multi-institutional, open assignment prospective study

Primary Outcome Measures:

1-year recurrence-free survival period in high-risk groups after sequential injection of Mitomycin-c 40 mg/20 ml and Gemcitabine 2000 mg/50 ml in non-muscle invasive bladder cancer patients in BCG-free high-risk groups.

Secondary Outcome Measures:

Progression Free Survival (PFS), Cystectomy free survival (CFS), Cancer specific survival (CSS), Overall survival (OS) and safety after Mitomycin-c 40mg/20ml and Gemcitabine 2000mg/50ml treatment in non-muscle invasive bladder cancer patients in BCG-free high-risk groups.

Inclusion criteria

• a patient over the age of 20
• Patients who are willing and able to complete a written test subject consent/approval for this examination.
• Histologically confirmed high-risk NMIBC (according to AUA guidelines; High-grade T1 disease, any recurrent high-grade Ta, high-grade Ta >3 cm, high-grade Ta that is multifocal, any carcinoma in situ, any BCG failure in high-grade patients, any variant histology, any lymphovascular invasion, and any high-grade prostatic urethral involvement) with prior BCG therapy.
• The most recent bladder examination/TURBT must be performed within 8 weeks before the initial administration of the trial treatment. Patients with high risk NMIBC who received proper BCG treatment but did not respond to BCG
• Patients who are not eligible for a radical bladder resection or who have refused surgery.
• Patient who are not being pregnant or breast feeding until the study period.

Exclusion criteria

• Patient diagnosed with muscle-invasive bladder cancer at TURBT
• If upper urinary tract urothelial cancer is accompanied by imaging
• If the imaging indicates extravesical involvement (cT3)
• Imaging shows lymph node metastasis (short-axis 15mm or more) or distant metastasis
• In a biopsy, non-transitional cell histology is dominant, or only non-transitional cell tissue is present (primary squamous cell carcinoma, primary adenocarcinoma, small cell carcinoma, sarcoma, carcinosarcoma, paraganglioma, melanoma, lymphoma)
• In the case of receiving systemic cytotoxic chemotherapy for other cancers within 3 years
• If patient have a history of pelvic radiation therapy for other cancers within 3 years
• If patient have a history of receiving Mitomycin-c or gemcitabine in the bladder within 3 years. The exception is cases used for the purpose of injection therapy of anticancer drugs in the early bladder cancer
• If patient has a history of allergy to mitomycin-c or gemcitabine
• Cystoscopy shows a tumor in the prostate urethra
• Patients who have participated in studies using clinical trial drugs and are currently receiving clinical trial drugs or who have used clinical trial drugs or clinical trial medical devices within 4 weeks prior to the date of initial treatment
• After post-cystoscopy/TURBT, the patient received intravesical chemotherapy prior to the start of trial treatment
• Thrombocytopenia, coagulopathy or bleeding tendency patient.
• Pregnant or breast-feeding women
• If patient treated yellow fever vaccine or phenytoin
• Dysfunction of liver or kidney (GFP≤30)
• If patient undergo severe myelosuppression
• If patient complicated severe infection
• If patient definitely diagnosed interstitial lung disease or lung fibrosis by chest X-ray.
• If patient conduct chest radiotherapy.