CONCURRENT PLATINUM AND DOCETAXEL CHEMOTHERAPY AND EXTERNAL RADICAL RADIOTHERAPY IN PATIENTS WITH INVASIVE TRANSITIONAL-CELL BLADDER-CARCINOMA - A PRELIMINARY-REPORT OF TOLERANCE AND LOCAL-CONTROL

Purpose: The present study aims to evaluate the feasibility toxicity, and efficacy of concurrent chemotherapy with cisplatinum and docetaxel , and external radical radiotherapy for transitional cell carcinoma of urinary bladder. Materials and Methods: 42 patients (34 men, 8 female s) with invasive bladder carcinoma (clinical stages T1-4) were treated after transurethral biopsy with chemotherapy and concomitant external radiotherapy. Chemotherapy consisting of cisplatin infusion (30mg/m2) and Docetaxel (40 mg/m(2)) was given twice a week simultaneously with -irradiation during the whole treatment period (6-8 weeks) as follows: Cisplatin (D-1, D-8, D-15, D-22, D-25, D-36, D-43, D-50) and Docetaxe l (D-4, D-11 D-18, D-25, D-32, D-39, D-46, D-53). An external irradiat ion scheme 1.8 to 2.0 Gy per fraction, 5 days a week was used up to 68 - 74 Gy (6MeV photons) total tumor dose. Results: All but S patients completed the planned chemoradiation protocol, The complete response r ate (CR - rate) assessed at 3 months after completion of combined trea tment was 100%, 63.6%, 46.15% and 95% for clinical stage (c) cT(1) (9/ 9), cT(2) (7/11), cT(3) (6/13) and cT(4) (1/4) cases respectively. Non e of 9 patients with T1 tumors had any local failure at 36.1 months me an follow-up time. In total 9 of 37 patients (24.32%) relapsed locally and/or distantly and were followed for 25.04 months (mean time). 50% of the relapses occured at a mean time of 7.25 months. The mortality r ate was 10.81% (4/37). All these patients died with a mean time of 11 months. 32 cases remain alive 19-46 months after treatment; 27 of thos e are with no evidence of disease with a mean follow - up time of 32.2 4 months. In total there was a 78.50% (30/37) and a 75.67%, (28/37) ra te of overall survival and pelvic control respectively at 25.04 months mean follow-up time. Chemotherapy was discontinued in 2 cases due to acute gastrointestinal toxicity and in 3 more, due to patient complian ce. There was 1 toxic death 2 months after treatment completion due to ureteral obstruction and impaired renal function. The acute toxicity was estimated as moderate to severe and caused the interruption of tre atment for 5 to 10 days in 8 of 37 patients (21.62%). Myelotoxicity ap peared in 22/37 patients but febrile grade III and IV neutropenia was observed in 3 patients (8.10%) and thrombocytopenia (Grade I - III) in 8 (21.62%). Concerning late effects a sigmoid stricture, a transient small bowel obstruction, 4 patients with contracted bladder and 1 case with renal failure were found Grade I to III hypersensitivity reactio ns appeared in 8/37 patients (21.62%) while stomatitis (grade I - II) and grade II skin toxicity appeared in 3 and 4 patients respectively T hese and other symptoms (Grade I to II peripheral edema, transient mya lgias and arthralgias in 7/37 cases), paresthesias or numbness (3/37) and peripheral motor dysfunction (1/37) were responsible for early red uction of docetaxel dose from 40 mg/m(2) to 20 mg/m(2). Conclusion: Th is preliminary analysis suggest that the radiosensitizing effect of ci splatin and docetaxel to megavoltage irradiation yielded a high CR - r ate in transitional cell bladder carcinoma patients with medium to sev ere early and late side effects. The value of such a combined treatmen t as far as the tumor eradication is concerned requires further evalua tion, because of the small number of patients, the short follow - up, and the absence of other studies using docetaxel as a radiosensitizer in urothelial cell cancer.