Tetsuo Omoto

Prophylactic intravesical instillation of mitomycin C and cytosine arabinoside for prevention of recurrent bladder tumors following surgery for upper urinary tract tumors: A prospective randomized study

Abstract Background: A recurrence of bladder tumors following surgery for transitional cell carcinoma of the upper urinary tract is not rarely observed. A prospective randomized study was conducted to examine the significance of prophylactic intravesical instillation of mitomycin C (MMC) and cytosine arabinoside (Ara‐C) to prevent recurrent bladder tumors after surgery for superficial transitional cell carcinoma of the upper urinary tract.

Postoperative UFT Adjuvant and the Risk Factors for Recurrence in Renal Cell Carcinoma: A Long-Term Follow-Up Study

Background Radical nephrectomy is the standard therapy for low‐stage renal cell carcinoma. However, recurrence sometimes develops even in patients who are considered to have undergone a curative resection of the primary tumor. The purpose of this study was to evaluate the usefulness of UFT (a 1: 4 mixture of tegafur and uracil) adjuvant and the risk factors for recurrence in renal cell carcinoma.

Postoperative prophylactic intravesical instillation of cytosine arabinoside and mitomycin C in superficial bladder tumor

A follow-up study was made on 225 Japanese patients with superficial bladder tumors who were treated postoperatively with intravesical instillation of cytosine arabinoside and mitomycin C nineteen times during one year. Cumulative recurrence rates of the tumor were 16.7 and 41.9 per cent during the first 1 and 3.5 years after surgery, respectively. These results are superior to the previous findings in cases in which instillation therapy was not given. Histologically, there was no definite difference in recurrence among the groups with low-grade and high-grade tumors. The recurrence rate of multiple tumors was higher than that of a solitary tumor. Earlier postoperative instillation appeared to be more effective during the initial one year after surgery.

Treatment of advanced hormone-refractory prostate carcinoma with a combination of etoposide, pirarubicin and cisplatin

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.

Early intravesical instillation of adriamycin with oral administration of 5-fluorouracil after transurethral resection for superficial bladder cancer: preliminary results.

SummaryIn 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 nonrecurrence 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.

Intravesical Therapy with Adriamycin plus Verapamil in Patients with Superficial Bladder Cancer: A Pilot Study

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.

Adjuvant chemotherapy with early intravesical instillation of Adriamycin and long-term oral administration of 5-fluorouracil in superficial bladder cancer

SummaryA randomized controlled trial was performed to study the efficiency of adjuvant chemotherapy with carly 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<0.01), tumor size of <1 cm (P<0.05), multiple tumors (P<0.01), pathological stage pTa (P<0.01), and histological grades G1 and G2 (P<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 instilations alone. The main side effect, which required discontinuation of the treatment, was bladder irriation. 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.

Significance of the Preoperative Intravesical Instillation of Doxorubicin and the Oral Administration of 5‐Fluorouracil in Preventing Recurrence After a Transurethral Resection 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.