Intravesical adjuvant chemotherapy for superficial transitional cell bladder carcinoma : results of 2 european organization for research and treatment of cancer randomized trials with Mitomycin C and Doxorubicin comparing early versus delayed instillations and short-term versus long-term treatment

Abstract

The European Organization for Research and Treatment of Cancer genitourinary group has completed 2 parallel prospective randomized studies, one with 30 mg. mitomycin C and the other with 50 mg.doxorubicin as adjuvant intravesical treatment after transurethral resection of superficial transitional cell bladder carcinoma.These studies were designed to compare early (the day of resection) versus delayed (between 7 and 15 days after resection) instillations and short-term (6 months) versus long-term (12 months) treatment.The results indicate that in regard to recurrence rate patients having a delayed and short-term treatment do worse than those having early instillations (for 6 or 12 months) or those having prolonged treatment (either immediate or delayed).With an average followup of 4 years survival, progression beyond T1 disease, development of distant mtastass and appearance of a second primary were not influenced by the therapeutic regimen.A multivariate analysis of prognostic factors is presented, which indicates that after adjustment for these factors, patients in the delay, no maintenance arm have a significantly higher recurrence rate than the other patients.Key Words: bladder neoplasms; carcinoma, transitional cell; chemotherapy, adjuvant Administration of adjuvant intravesical chemotherapy or immunotherapy is a common practice today for the prophy laxis of recurrent superficial bladder cancer.Among the dif ferent agents used for this purpose, thiotepa, mitomycin C and doxorubicin have been shown to be active.1Regimens based on these adjuvant treatments have often been estab lished on an empirical basis, and are a compromise between potential toxic effects and aimed benefits.Many questions still remain unanswered in relation to the scheme of instil lation.When is the ideal time to start the treatment?What is the ideal dosage at each instillation?What is the optimal duration of the treatment?What is the ideal interval between 2 instillations?2In 1983 the genitourinary group of the European Organi zation for Research and Treatment of Cancer (EORTC) started 2 parallel trials, one with mitomycin C (protocol 30831) and one with doxorubicin (protocol 30832) to try to answer 2 questions: 1) what is the best time for initiation of adjuvant intravesical treatment and 2) how long should the drug be administered for prophylactic purpose after complete transurethral resection of superficial bladder cancer?The final results of these 2 studies are reported.