Early and large-dose intravesical instillation of epirubicin to prevent superficial bladder carcinoma recurrence after transurethral resection.
OBJECTIVE
To prospectively compare the prevention of tumour recurrence by four intravesical adjuvant administration protocols, and thus elucidate the efficacy of early and high total dose instillations of epirubicin to prevent superficial bladder tumour recurrence after transurethral resection of bladder tumour (TURBT).


METHODS
In all, 69 patients with Ta/T1 bladder cancer were randomly assigned to four intravesical administration protocols: A, delayed instillation (first instillation 7 days after TURBT) and low-dose (30 mg once every 2 weeks, six times): B, early instillation (three instillations before 7 days after TURBT) and low-dose; C, delayed and high-dose (30 mg once weekly 12 times) instillation; D, early and high-dose. The influence of the instillation protocols and tumour characteristics on the probability of recurrence-free survival was examined using Kaplan-Meier analysis and a Cox regression hazard model.


RESULTS
The early-instillation and high-dose groups had relatively lower recurrence rates after 6 months (A, 30%; B, 25%; C, one of 12; and D, none) and 1 year (50%, 35%, four of nine and one of eight, respectively). Patients who received 360 mg epirubicin (C and D) had a significantly better recurrence-free survival than those receiving 180 mg (A and B; P = 0.012). Preoperative urine cytology and tumour multiplicity were significantly associated with recurrence. However, multivariate analysis of the risk of recurrence using a Cox proportional hazard model showed that urine cytology (hazard ratio 3.11, 95% confidence interval 1.08-8.94, P = 0.04) and total dose (0.32, 0.11-0.92, P = 0.03) were independent prognostic factors for recurrence.


CONCLUSIONS
Patients who received a high-dose epirubicin instillation had a significantly lower recurrence rate but the benefit of early instillation was not confirmed, as the study group was too small.
Mitsumori
Kenji
K
Department of Urology, Akita University School of Medicine, 1-1-1 Hondo, Akita City, Akita 010-8543, Japan.
Tsuchiya
Norihiko
N
Habuchi
Tomonori
T
Li
Zhenhua
Z
Akao
Toshiya
T
Ohyama
Chikara
C
Sato
Kazunari
K
Kato
Tetsuro
T
D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D015251:Epirubicin / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D011446:Prospective Studies; D001749:Urinary Bladder Neoplasms / Q000517:prevention & control* / Q000601:surgery
D000903:Antibiotics, Antineoplastic; D015251:Epirubicin