Alternating mitomycin C and BCG instillations versus BCG alone in treatment of carcinoma in situ of the urinary bladder: a nordic study.
OBJECTIVE
To evaluate whether, in patients with carcinoma in situ (CIS) of the urinary bladder, alternating instillation therapy with mitomycin C (MMC) and bacillus Calmette-Guerin (BCG) was more effective and less toxic than conventional BCG monotherapy.


METHODS
Patients were stratified prospectively for primary, secondary, and concomitant CIS and randomized to one of two regimens. Patients in the alternating group received six weekly intravesical instillations of MMC 40 mg, followed by alternating monthly instillations of BCG 120 mg and MMC for one year. In the monotherapy group, only BCG was instilled on the same schedule.


RESULTS
Of 323 enrolled patients, 304 were eligible for analysis. After an overall median follow-up of 56 months, the Kaplan-Meier disease-free estimate for BCG monotherapy was significantly better than that for alternating therapy (p=0.03; log rank test). Risk for progression appeared lower in the BCG monotherapy group (p=0.07), but no differences existed in survival. Besides the regimen, CIS category also predicted outcome to some extent. BCG monotherapy caused significantly more local side-effects and premature cessation of instillation treatment than did the alternating therapy. However, no differences were observed in the number of serious side-effects.


CONCLUSIONS
One-year BCG monotherapy was more effective than the alternating therapy for reducing recurrence and compared well with the best regimens reported from substantially smaller series. The alternating therapy was better tolerated.
Kaasinen
Eero
E
Department of Surgery, Hyvinkää Hospital, Sairaalakatu 1, FIN-05850 Hyvinkää, Finland. eero.kaasinen@hus.fi
Wijkström
Hans
H
Malmström
Per Uno
PU
Hellsten
Sverker
S
Duchek
Milos
M
Mestad
Oddvar
O
Rintala
Erkki
E
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000283:Administration, Intravesical; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000008:administration & dosage*; D002278:Carcinoma in Situ / Q000188:drug therapy / Q000628:therapy*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D016685:Mitomycin / Q000008:administration & dosage / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D012537:Scandinavian and Nordic Countries; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000628:therapy*
D000276:Adjuvants, Immunologic; D000903:Antibiotics, Antineoplastic; D001500:BCG Vaccine; D016685:Mitomycin