Prophylactic intravesical instillation chemotherapy against recurrence after a transurethral resection of superficial bladder cancer: a randomized controlled trial of doxorubicin plus verapamil versus doxorubicin alone. The Kyushu University Urological Oncology Group.
OBJECTIVE
We investigated whether verapamil (VR), a known chemosensitizing agent of P-glycoprotein-mediated multidrug resistance, could enhance the preventative effect of doxorubicin (Adriamycin, ADM) on both intravesical recurrence and disease progression after transurethral resection (TUR) of superficial bladder cancer.


METHODS
The patients were randomized into two groups: one group received an intravesical instillation of ADM (30 mg) plus VR (15 mg) after TUR of superficial bladder cancer (19 times over 1 year), and the other group received ADM alone on the same treatment schedule. The nonrecurrence rate, the incidence of disease progression at the first recurrence and the side effects were compared over a median follow-up of 38.5 months.


RESULTS
Of the 226 patients registered, 157 were evaluable. No significant differences were observed in the patients' characteristics between the two groups. Although the incidence of disease progression at the first recurrence was not significantly different between the two groups, the ADM plus VR instillation group did show a significantly higher nonrecurrence rate than the ADM-only instillation group, and such significance persisted even when any possible bias was allowed for in a multivariate analysis. In terms of side effects, the incidence and severity of bladder irritation symptoms were not significantly different between the two groups.


CONCLUSIONS
Intravesical instillation chemotherapy with ADM plus VR was found to have a significantly greater beneficial effect than with ADM alone for preventing recurrence after TUR of superficial bladder cancer.
Department of Urology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
S
S
Naito
S
S
Kotoh
T
T
Omoto
Y
Y
Osada
K
K
Sagiyama
A
A
Iguchi
A
A
Ariyoshi
Y
Y
Hiratsuka
J
J
Kumazawa
D000283:Administration, Intravesical; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000517:prevention & control* / Q000601:surgery; D014700:Verapamil / Q000008:administration & dosage
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D014700:Verapamil