a phase ii trial evaluating an organ-conserving strategy by radiochemotherapy for muscle-infiltrative bladder cancer

Conditions: Infiltrating Bladder Urothelial Carcinoma

Summary: if radical cystectomy remains the standard of care for muscle invasive bladder cancer, consequences of this surgical procedure are often harsh. over the past years, concurrent chemo-radiotherapy has imposed itself as an alternative treatment. published data on concomitant radiochemotherapy (radiotherapy/cisplatin or radiotherapy/cisplatin/5-fluorouracil combinations) showed local control rates with bladder preservation at 5 years ranging from 40% to 65% according to the disease stage, and overall survival probabilities ranging from 40% to 50% at 5 years. in order to improve local and systemic prognosis, evaluation of other chemotherapy agents with higher radiosensitizing effect, such as gemcitabine, is justified. gemcitabine possesses its own anti-cancer activities on urothelial diseases and has a synergetic activity with cisplatin. the investigators completed a monocenter phase i study combining radiotherapy, cisplatin, and twice-weekly gemcitabine, and determined a recommended dose of gemcitabine 25 mg/m². the objective of the present study is to evaluate the combination of radiotherapy + cisplatin + gemcitabine in terms of disease-free survival in non metastatic muscle invasive urothelial cancer patients.

the objective of the present study is to evaluate the combination of radiotherapy + cisplatin + gemcitabine in terms of disease-free survival in non metastatic muscle invasive urothelial cancer patients.

Eligibility criteria:
inclusion criteria: * muscle invasive urothelial cancer (front line or following the progression of a superficial tumor), pt2-pt3 stage without lymphatic impairment (n0) and without detectable metastases (m0). an optimal macroscopic resection (turb) have to be performed * the proof of invasive tumor to the muscle should be brought by a transurethral resection under anaesthesia less than 8 weeks before or, in the absence, by superficial biopsies and formal imaging. multiples biopsies in the bladder must also be performed. * age ≥ 18 years * life expectancy ≥ 6 months * kanorfsky index ≥ 70 % (who 0, 1, 2) * biological criteria: neutrophils ≥ 1500/mm3, platelets ≥ 100 000/mm3, haemoglobin ≥ 10 g/dl, creatinine clearance \> 60 ml/mn * no distant metastases (thorax, abdomen, and pelvic ct-scan, bone scan) * efficient contraception for premenopausal women, maintained during the whole treatment and up to two months after the completion of radiotherapy. * no radiotherapy or chemotherapy history except for in situ bladder lesions. * no carcinological history except for non melanoma skin tumours, in situ uterine cervix cancer * no contraindication to gemcitabine or cisplatin. * no contraindication to radiotherapy * information letter and informed consent signed * patient covered by social security exclusion criteria: * bladder tumors without any muscle infiltration * epidermoid carcinoma or adenocarcinoma * distance metastases or extrapelvic node positivity * severe digestive history (ulcerative colitis, complicated diverticulitis) * pregnancy and breast feeding

Keywords: bladder cancer organ-conserving strategy radiochemotherapy non metastatic