Kazuya Tashiro

Long-term results of intravesical chemoprophylaxis of superficial bladder cancer: experience of the Japanese Urological Cancer Research Group for Adriamycin.

SummaryLong-term results were analyzed in terms of tumor progression and survival in patients with superficial bladder cancer who were enrolled in the second intravesical chemoprophylactic study of the Japanese Urological Cancer Research Group for Adriamycin, which was started in July 1982. This study was a prospective, randomized, controlled trial conducted on primary tumors treated with a long-term instillation regimen that involved control versus intravesical instillations of Adriamycin or mitomycin C given once a week for the first 2 weeks, once every other week for 14 weeks, once a month for 8 months, and once every 3 months for 1 year, for a total of 21 instillations in 2 years. An analysis of the prophylactic effects of such treatment on bladder tumors after TUR has previously been performed, and the results have been published elsewhere. The present study represents a follow-up of the above trial. Of the 671 cases previously analyzed with regard to tumor prophylaxis, 158 cases (23.5%) were eligible to be followed for tumor progression and survival. A detailed comparison of the background factors between these 158 patients and the other 513 cases revealed no statistically significant difference. Thus, the 158 evaluable cases might reasonably be considered to represent all patients enrolled in the second study, and the results were thought to be reasonable enough to reflect the long-term efficacy of the long-term instillation regimen adopted in this study. The median follow-up for these 158 cases was 6.6 years. Tumor progression in terms of the disease stage and/or grade occurred in 43 of 127 patients who received prophylactic instillations and in 12 of 31 control cases. No significant difference in the incidence of tumor progression was found between the treatment and the control groups. In addition, no difference in survival was observed between the treatment group and the control group. Survival was also compared between patients who showed tumor progression and those who did not. All patients whose tumors did not progress survived, whereas the 7-year survival of those exhibiting tumor progression was <90%.

The 4th study of prophylactic intravesical chemotherapy with Adriamycin in the treatment of superficial bladder cancer: the experience of the Japanese urological cancer research group of Adriamycin

SummaryA multicentric randomised trial was conducted for the purpose of investigating the efficacy of intravesical chemoprophylaxis of superficial bladder cancer. A total of 443 patients (number of evaluable patients, 284) were registered from July 1987 to December 1989 and randomised into 3 groups. Group A received 21 intravesical instillations of Adriamycin (ADM) at 20 mg/40 ml physiological saline for 2 years after undergoing transurethral resection (TUR); group B was given the same dose as group A but received 6 intravesical instillations for 2 weeks before undergoing TUR; and group C served as a control and underwent TUR only. Better prophylactic effects were obtained in group A. The overall non-recurrence rates calculated for groups A and B differed significantly (P<0.05) on day 240, and those determined for groups A and C were also significantly different (P<0.01) on day 480. No benefit was obtained using intravesical instillation prior to TUR (group B). The major side effects encountered were pollakisuria and miction pain, which occurred in 32% of the patients in group A and in 52% of those in group B.

Prophylactic chemotherapy with intravesical instillation of Adriamycin and oral administration of 5-fluorouracil after surgery for superficial bladder cancer

The Japanese Urological Cancer Research Group for Adriamycin has conducted a series of clinical trials to investigate the efficacy and safety of prophylactic intravesical chemotherapy for superficial bladder cancer. In the third trial, reported herein, patients with recurrent bladder cancer or multiple primary cancer were selected and randomized to one of four groups using the envelope method after complete resection of the original tumors. Group A was given Adriamycin alone, group B received oral 5-fluorouracil (5-FU), group C was given Adriamycin and oral 5-FU, and group D served as the control group. Of the 544 patients registered, 331 were evaluable for the purpose of this study. The administration of 5-FU (group B) failed to prevent the recurrence of bladder tumors. Although group C (both Adriamycin and 5-FU) did not fare better than group A (Adriamycin only), Adriamycin was effective in preventing the recurrence of tumors, especially in high-risk patients with recurrent and multiple tumors. The risk of recurrence was reduced to 0.21 (95% confidence interval, 0.10–0.44) relative to the control group. There was no indication of a synergistic effect between 5-FU and Adriamycin. As side effects, cystitis syndrome was observed in 23%–30% of the patients in the Adriamycin groups and mild myelosuppression was observed in the 5-FU groups.

Evaluation of systemic chemotherapy with methotrexate, vinblastine, Adriamycin, and cisplatin for advanced bladder cancer*

SummaryIn a cooperative study of the Japanese Urological Cancer Research Group for Adriamycin, the usefulness of chemotherapy with methotrexate, vinblastine, Adriamycin, and cisplatin (M-VAC therapy) in treating advanced or recurrent bladder cancer was examined. Evaluation of the clinical responses obtained in 86 evaluable patients revealed 13 complete responses, 29 partial responses, 4 minor responses, 19 cases of no change, and 21 cases of progressive disease. The overall response rate was 48.8% (42/86). The rate of response to M-VAC therapy at each disease site was as low as 21.4% (3/14) in bone lesions but exceeded 40% in the primary lesion, the lymph nodes, the lung, the liver, and other lesions. The clinical response to M-VAC therapy was not significantly influenced by the performance status of the patients, the dose intensity, or previous therapy. The median duration of response for the 42 responders was 22.7 weeks (range, 8.1–134.1 weeks), and the median duration of survival for the 86 evaluable patients was 9.8 months. Side effects were frequently encountered; the patients experienced anorexia, nausea, vomiting, malaise, alopecia, and leukopenia, but all of these symptoms were tolerable.

Phase III trial of The Japanese Urological Cancer Research Group for Adriamycin: cyclophosphamide, adriamycin and cisplatinum versus cyclophosphamide, adriamycin and 5-fluorouracil in patients with advanced transitional cell carcinoma of the urinary bladder

SummaryA non-randomized clinical study on systemic combination chemotherapy was conducted by the Japanese Urological Cancer Research Group for Adriamycin to compare the effectiveness of CAP (cyclophosphamide 200–500 mg/m2, adriamycin 30–50 mg/m2 and cisplatin 30–50 mg/m2) and CAF (cyclophosphamide 200–500 mg/m2, adriamycin 30–50 mg/m2 and 5-fluorouracil 250 mg/m2) in 123 patients (104 evaluable) with advanced and/or metastatic cancer of the urinary bladder. Among 96 patients who were non-randomly selected to receive CAP, 4 achieved complete remission, 12 achieved partial remission, 7 achieved minor response, 30 had stable disease, and 43 had disease progression. The response in the 8 patients who received CAF were: partial remission in 1 and progressive disease in 7. The overall response rate to CAP therapy was 17%, as against 13% for CAF therapy. The median duration of survival with CAP was 29 weeks and with CAF, 22 weeks. The differences between the two groups in duration of survival and response rate were not statistically significant. Complete and/or partial remissions were observed in the lymph nodes, lung and liver in 32%, 24%, and 57% of cases, respectively. There was no objective response in bone metastasis. The main side effects of CAP were anorexia (88%), nausea and/or vomiting (81%), alopecia (65%), leukopenia (72%), anemia (48%), and renal dysfunction (17%). No patients died as a result of toxicity of these combination chemotherapy modalities.

Combination chemotherapy for advanced bladder cancer with adriamycin, cyclophosphamide, and 5-fluorouracil.

SummaryCombination three-drug chemotherapy with adriamycin (ADM), cyclophosphamide (CPM), and 5-fluorouracil (5-FU) was performed in 24 cases of advanced bladder cancer who underwent surgical treatment, and three cases with recurrent or metastatic bladder cancer. The average age (25 men and 2 women) was 53. Of the 24 cases, nine were in stage T2, 10 in T3, and five in T4.One course consisted of a combination of 30 mg/m2 of ADM, 300 mg/m2 of CPM, and, 250 mg of 5-FU, administered five times. The combination was administered to three groups: every day for 5 days consecutively in group A, twice a week for 21/2 weeks in group B, and once every 4 weeks for 16 weeks in group C. After injection of ADM, CPM, and 5-FU, 200 mg/day of 5-FU was administered PO daily in all three groups.The 5-year survival rate of the 24 cases (apart from 3 cases with measurable metastatic tumor) was 58%. The 5-year survival rate for stage T2 was 88%, and that for stage T3 was 62.5%; all patients with stage T4 disease died before 3 years and 6 months. Partial response was seen in two out of three patients with recurrent or metastatic disease.Alopecia was observed in all cases as a side-effect of the chemotherapy. Also anorexia, nausea, and myelosuppression were observed in many cases, though the degree was tolerable. However, there were no disorders of the cardiovascular system, except for one case with transient hypotension.

A clinical study of secondary osteoporosis induced by endocrine therapy for prostate cancer

PURPOSE There is one of the big problems that endocrine therapy for prostate cancer causes to induce secondary osteoporosis. The risk factors and future treatments for osteoporosis were investigated. MATERIALS AND METHODS 31 patients treated with luteinizing hormone releasing hormone agonists (LHRH-a) or combination of chlormadinone acetate (CMA) and LHRH-a, and 19 patients with no treatments for prostate cancer were included in the analysis. Lumber spine bone mineral density (BMD) was measured by quantitative computed tomography. RESULTS Aging had much influence on decreases of BMD than the other risk factors (p < 0.01). There were statistically decreases of BMD in the patients with CMA + LHRH-a compared with no treatments (p < 0.05). Adrenal androgen which had an important role of maintenance in BMD was statistically decreased by the administration of CMA (p < 0.01). CONCLUSIONS Measurement of BMD before endocrine therapy is necessary for the patients with prostate cancer. It is important for the patients with decreases of BMD that CMA is not combined or the therapy for osteoporosis is preventively employed.

AN ANALYSIS OF FACTORS RELATED TO RECURRENCE OF SUPERFICIAL BLADDER CANCER AFTER TRANSURETHRAL RESECTION

A total of 205 patients with primary superficial bladder cancer (Ta, T1) followed more than 3 years were retrospectively analyzed for factors related to recurrence of tumors after transurethral resection. Patients age were 25 to 90 years old, average 61 years old, and there were 160 males and 45 females. Initial tumor grades were G0 in 4 patients, G1 in 48, G2 in 134 and G3 in 19. Seventy four patients had Ta tumor and 131 had T1. Initial treatments were transurethral resection (TUR) alone in 137 patients. TUR with intravesical chemotherapy in 64, with BCG therapy in 7 and others in 7. Factors examined included age, sex, chief complaint, shape, size, and number of tumors, tumor distribution (single area or multiple area), histological grade, stage and intravesical chemotherapy. Overall non-recurrent rate were 81.7% at 1 year, 60.7% at 3 year, 53. 8% at 5 year and 44.2% at 8 year. Five-year non-recurrent rate according tumor factors, showed significant difference regarding tumor size (< 1 cm or 1 cm <: P = 0.027), tumor number (single or multiple: P = 0.004), tumor distribution (single area or multiple area: p = 0.002), histological grade (< G1 or G2 < : p = 0.001) and stage (Ta or T1: p = 0001). However, there were no significant difference regarding factors of age, sex, chief complaint, tumor figure and presence or absence of intravesical chemotherapy. This results suggested that the tumor factors of size, number, tumor distribution, grade and stage were highly related to intravesical tumor recurrence of superficial bladder cancer.