Search

Purpose: 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.

Background: The postoperative intravesical instillation of doxorubicin (ADM) has a preventative effect on recurrence after a transurethral resection (TUR) of superficial bladder cancer. However, the significance of preoperative ADM instillation remains unclear. Although the oral administration of 5-fluorouracil (5-FU) has been observed to show some clinical response against bladder cancer, its preventative effect on the recurrence of superficial bladder cancer after TUR is unknown., Methods: Patients were randomized into 4 groups. All 4 groups received postoperative ADM instillation. In addition, patients in groups C and D received preoperative ADM instillation, whereas patients in groups B and D additionally received oral 5-FU postoperatively. The nonrecurrence rate and side effects were both compared among the 4 groups., Results: Of the 282 patients registered, 200 were evaluable, with a median follow-up period of 21.4 months. There were no significant differences in the characteristics of the patients among the 4 groups. Group C (pre- and postoperative ADM) showed a significantly longer disease-free interval than group A (postoperative ADM alone). However, there was no significant difference in the disease-free interval between groups A and B (postoperative ADM plus 5-FU), or between groups C and D (pre- and postoperative ADM plus 5-FU). Bladder irritation symptoms were the most frequently noted side effect encountered in all groups, but the severity was generally mild., Conclusions: Preoperative ADM instillation was found to prevent recurrence to a greater extent than the usual postoperative instillation alone, whereas oral 5-FU was found to have no additional beneficial effect on the disease-free interval in patients with superficial bladder cancer.

A prospective randomized trial was conducted to compare the prophylactic effect of intravesical installation of Adriamycin (ADM) plus verapamil (VR) with that of ADM alone for recurrence of superficial bladder cancer. A total of 226 patients were enrolled and randomized into 2 groups. Group A received intravesical instillation of ADM (30 mg/30 ml physiological saline) on 19 occasions during a 1-year period after transurethral resection, whereas group B received intravesical instillation of ADM (30 mg/24 ml physiological saline) plus VR (15 mg/6 ml saline) according to the same schedule used for group A. Evaluation was possible in 157 of the 226 registered patients (group A, 76; group B, 81). There was no significant difference in the patients' characteristics between the two groups, and there was no significant difference in the overall nonrecurrence rate determined over a 24-month follow-up period. However, group B showed a significantly higher nonrecurrence rate than did group A for tumors measuring less than 1 cm in diameter (P < 0.05) and for histological grade 2 tumors (P < 0.01) in spite of there being no significant difference in the other characteristics of each subgroup of patients. The incidence and severity of side effects were similar in both groups, and VR caused no significant systemic toxicity. Although further follow-up is necessary, these results suggest that intravesical instillation of ADM plus VR is clinically safe and may be more effective than instillation of ADM alone in preventing the postoperative recurrence of superficial bladder cancer (less than 1 cm in diameter, histological grade 2).

A randomized controlled trial was performed to study the efficiency of adjuvant chemotherapy with early intravesical instillation of Adriamycin and long-term oral administration of 5-fluorouracil in 275 patients with superficial bladder cancer. All of the patients were randomized into four groups. Group A received early (immediately and 2 days after transurethral resection) instillation of Adriamycin alone; Group B received early instillation of Adriamycin with oral administration of 5-fluorouracil; Group C received delayed (7 days after transurethral resection) instillation of Adriamycin alone; and group D received delayed instillation of Adriamycin with oral administration of 5-fluorouracil. All patients subsequently received instillations weekly for 2 weeks and then every 2 weeks for a further 14 weeks. After 4 months, they received monthly instillations for 8 months. 5-Fluorouracil (groups B and D) was given daily p.o. for 1 year. Evaluation was possible in 187 patients. The postoperative follow-up period for determination of non-recurrence rates was 36 months, during which no significant difference was detected among the four groups. Moreover, no statistically significant difference was found between the early- and delayed-instillation groups. However, the non-recurrence rates obtained in the groups undergoing early instillation were higher than those determined in the delayed-instillation groups during the 36-month follow-up period, and this difference was especially significant at 4 and 5 months. In addition, the early-instillation groups showed significantly higher non-recurrence rates than did the delayed-instillation groups in terms of primary cases (P less than 0.01), tumor size of less than 1 cm (P less than 0.05), multiple tumors (P less than 0.01), pathological stage pTa (P less than 0.01), and histological grades G1 and G2 (P less than 0.05). Groups B and D, which were treated by intravesical instillation of Adriamycin with oral administration of 5-fluorouracil, showed no significant prophylaxis of recurrence during the 36-month follow-up as compared with groups A and C, which received intravesical instillations alone. The main side effect, which required discontinuation of the treatment, was bladder irritation. However, no significant difference in its incidence was found between the early- and delayed-instillation groups. No severe systemic side effect was encountered in this study. These results suggest that early as well as repeated intravesical instillation of Adriamycin is clinically tolerable and may be effective in preventing the recurrence of superficial bladder cancer.

Nineteen patients with histologically proven superficial bladder cancer (Ta, T1) were treated with intravesical instillation of 30 mg of adriamycin (ADM) dissolved in 24 ml physiological saline plus 15 mg of verapamil (VR) (6 ml) every day for 10 days. In spite of the short period of treatment, 6 of the 18 evaluable patients (33.3%) showed complete response (CR) and a further 5 (27.8%) showed partial response (PR). Five of the 6 patients with CR were recurrent cases who had previously received prophylactic intravesical instillation chemotherapy including ADM. Irritative urinary symptoms were observed in 11 of the 19 patients (57.9%). However, these symptoms were mild in the majority of patients and the treatment was completed without interruption in all but 1 patient. There was no significant absorption of ADM and VR into the systemic circulation. No clinical evidence of systemic toxicity was observed. These results suggest that combination of ADM and VR has a possibility to be a useful prophylactic intravesical instillation chemotherapy after endoscopic resection of not only primary but also recurrent chemoresistant bladder cancers.

In all, 199 patients were entered in this study by 21 collaborating hospitals. Patients with superficial transitional cell carcinoma of the bladder were randomized postoperatively into four groups. Group A received early (immediately and 2 days after transurethral resection) instillation of adriamycin (30 mg/30 mg); group B received early instillation of adriamycin with oral administration of 5-fluorouracil (200 mg/day); group C received delayed (7 days after transurethral resection) instillation of adriamycin (30 mg/30 ml); and group D received delayed instillation of adriamycin with oral administration of 5-fluorouracil (200 mg/day). All patients subsequently received instillations weekly for 2 more weeks, and then every 2 weeks for a further 14 weeks. After 4 months, they received one instillation per month for 8 months. 5-Fluorouracil was administered p.o. for 1 year. The postoperative follow-up period was 12 months. After 3 and 6 months there were significant differences in the non-recurrence rates between groups B and C. After 12 months the overall non-recurrence rates were 87.9% in group A, 83.5% in group B, 89.2% in group C, and 82.8% in group D, and there were no significant differences among the four groups. The number of patients entered and the follow-up period are not adequate for firm conclusions, and further studies are necessary. The main side effect was bladder irritation, which was observed in 38.8% of patients in the early instillation groups and in 26.3% of those in the delayed instillation groups. No severe systemic side effects were observed in this study.

A total of 20 patients with hormone-refractory prostate carcinoma entered a pilot study of combination chemotherapy based on the EAP (etoposide, Adriamycin and cisplatin) regimen, in which Adriamycin was replaced by pirarubicin, a less cardiotoxic derivative of Adriamycin. The response was assessed by criteria modified from those of the National Prostatic Cancer Project: prostate-specific antigen was employed instead of acid phosphatase. Of 18 evaluable patients, 6 achieved a partial response, 5 had stable disease, and in 7 the disease had progressed during therapy; thus, the overall response rate was 33.3% [95% confidence interval (CI) 11.5-55.1%]. Significant pain alleviation and performance status improvement were obtained in 5 of 12 patients (41.7%; CI 13.8-69.6%) and 3 of 13 patients (23.1%; CI 0.2-46.0%), respectively. Although myelosuppression was moderate to severe, no chemotherapy-related deaths or bacteriologically documented sepsis occurred; nor was there any clinical cardiotoxicity. All the responding patients received maintenance chemotherapy with etoposide thereafter. At present, the median duration of response is 33 weeks (range: 23-91 weeks) and the median survival period for all patients is 42 weeks (range: 27(+)-136 weeks), with 12 deaths. In spite of the small number of patients treated, these results suggest that this chemotherapy regimen is active in advanced hormone-refractory prostate carcinoma. [ABSTRACT FROM AUTHOR]