Recently, various progresses have been made in the treatment of the genitourinary malignant tumors. Effectiveness of the intravesical instillation of anti-cancer agents and biological reaction modifiers has been proved in the treatment and prevention of the superficial bladder cancer. Among them, superiority of BCG is now attracting attention of all the urologists. For the invasive bladder cancer, the M-VAC therapy (the combination chemotherapy of methotrexate, vinblastine, actinomycin and cis-platinum) has been found to be extremely useful. The multidisciplinary approach for the down-staging of the advanced bladder cancer has been advocated around the world. As for the prostatic cancer, that of the high stage is the main concern of the Japanese urologists, since the mass screening of the prostatic cancer has not prevailed in Japan. The LHRH agonists or the blockers of the androgen receptor have been replacing the classic antiandrogenic treatment consisting of castration and estrogen administration to treat the advanced carcinoma. On the other hand, the nerve-sparing total prostatectomy has been recommended for the low stage cancer by Walsh and associates to preserve potency. The testicular cancer has been most effectively treated with the combined chemotherapy. The PVB and VAB therapy are well known in the world. Lately, VP-16 (etoposide) was found to be a useful salvage agent. The least advance has been made in the treatment of renal cell carcinoma, although interferon therapy or LAK cell adoptive immunotherapy appears attractive.

Administration, Intravesical↗

PubMed1988

[Endocrine therapy of prostatic carcinoma with slow release (depot) formulation of the LH-RH analog ICI 118630 (Zoladex)].

To investigate the clinical efficacy, safety and endocrinology of ICI 118630 (Zoladex) depot formulation at 3 different dose levels (0.9, 1.8 and 3.6 mg), 90 patients were randomized to receive either one of the 3 doses from April, 1985 to March, 1986 in 28 centers. The depot preparation was injected subcutaneously every 4 weeks 3 times (for up to 12 weeks). Clinical efficacy was evaluated in terms of tumor response and overall subjective response. In 70 patients eligible for tumor response evaluation, 14 out of 22 (63.6%) in the 0.9 mg group, 11 out of 23 (47.8%) in the 1.8 mg group, and 17 out of 25 (68.0%) in the 3.6 mg group showed clinical improvement, that is, either complete response or partial response. In 72 eligible patients for overall subjective response evaluation, clinical subjective improvement was observed in 75.0, 81.8 and 88.0% of the patients in the 3 groups, respectively. There was no significant difference between the groups. As for endocrinology, there were 75 eligible patients. Endocrinological effect was observed in 23 out of 25 (92.0%) in the 0.9 mg group, 100% in both 1.8 mg and 3.6 mg groups. There was no significant difference between the groups. Castration was achieved by week 3.5 +/- 1.7 of therapy on average and by week 2 in the earliest case. There was no significant difference in incidence of side effects between the 3 groups: 5 out of 26 (19.2%) in the 0.9 mg group, 8 out of 29 (27.6%) in the 1.8 mg group, and 2 out of 30 (6.7%) in the 3.6 mg group. Flares presented as an increase in bone pain in 2 and as ureteric obstruction in 2 all in the 1.8 mg group but none in the other 2 dose groups. These flares disappeared on further treatment with Zoladex. These patients showed a clinical-response. The blood level of Zoladex was dose dependent, reaching its peak at week 2 of therapy in all 3 dose groups. There was no evidence of accumulation. Since these results demonstrate that 3.6 mg produces medical castration earlier, it may well be considered as an optimal dose in men.

Buserelin↗

PubMed1988

[Clinical efficacy of long-term treatment with LH-RH analogue, ICI 118630 (Zoladex), in prostatic cancer patients. The Zoladex Multicenter Study Group].

The Zoladex (ICI 118,630) multicenter trial included 149 patients with stage B +o D prostatic cancer recruited from 1984 to date. Of them 53 clinical responders on the treatment for 40 weeks or longer were subjected to assessment of antitumour response, overall subjective response, endocrinological response, safety and usefulness. The responders consistently showed a clinical response as evidenced by antitumour response in 32 of 50 patients (64.0%) at week 12 and in 35 of 51 (68.6%) at week 40, and overall subjective response in 42 out of 47 patients (89.4%) at both week 12 and week 40. Endocrinologically, all of the 47 eligible patients maintained a 40-week or longer response. Adverse reactions were observed in 19 out of 73 patients (26.0%), subdivided by the time of occurrence as 15/73 (20.5%) up to week 12, 3/71 (4.6%) between week 12 and week 40, and 5/53 (9.4%) in and after week 40. No patient required the discontinuance of treatment. Usefulness of the drug was observed in 51 out of 52 patients (98.1%). The results indicated that Zoladex in a once monthly regimen may be of great advantage to elderly patients with prostatic cancer, and allow an improved patient compliance: Zoladex may not only produce clinical remission but also improve the quality of life.

Buserelin↗

PubMed1988

[Endocrine therapy for prostatic carcinoma--the clinical trial to compare the efficacy of LH-RH analogue, ICI 118630 (Zoladex) with castration or estrogen].

A multicenter randomized clinical trial was carried out between May, 1986 and May, 1987 involving 82 patients with stage B-D prostatic carcinoma from 29 centers. The clinical efficacy, endocrine effect, safety and usefulness of the luteinizing hormone-releasing hormone (LH-RH) analogue and other endocrine manipulations in the treatment of prostatic carcinoma. Zoladex depot containing 3.6 mg of ICI 118,630, an LH-RH analogue, was administered every four weeks 3 times in total. Patients in the control group received either 300 mg of diethylstilbestrol diphosphate orally daily for 12 weeks or orchidectomy. An antitumor effect (CR + PR) was observed in 21 of the 33 patients (63.6%) in the Zoladex group and in 22 of the 33 (66.7%) in the control group, showing no significant difference between the two groups. There was no significant difference in overall subjective response either; 21 of the 24 (87.5%) in the Zoladex group and 24 of the 30 (80.0%) in the control group. In both groups, 100% endocrine effect was obtained as shown by achievement of castration in all patients. Adverse reactions were observed in 14 of the 39 (35.9%) patients treated with Zoladex as compared with 19 of the 34 (55.9%) control patients, resulting in no significant difference in the incidence between the two groups. These adverse reactions were not so severe as to require withdrawal from the study. In both groups, the treatment was assessed as slightly or more useful in 29 of the 33 (87.9%) patients. From these results, it is concluded that Zoladex, 3.6 mg depot, is a useful drug for treatment of prostatic cancer, having clinical efficacy and endocrine effects comparable to those of the conventional endocrine manipulations, being safe, and causing less physiological and psychological pain.

Aged↗

PubMed1988

Flexible ureterorenoscopy.

The clinical applications of flexible ureterorenoscopes have fallen behind those of their rigid counterparts. Flexible endoscopes that possess a working channel and can also be employed for treatment have at last been developed. This instrument is particularly effective in the treatment of stones in the upper urinary tract, as it can easily follow mobile upper ureteral stones and calculi in the middle or lower renal calices, which are not as accessible with a rigid endoscope. It is important to remember not to exert too much force when inserting the instrument into the ureter, renal pelvis, or renal calices, and, if one remains calm, should the visual field become temporarily obscured, there should be little danger of damaging these structures. This method will probably be increasingly employed, not only for the treatment of stones in the upper urinary tract, but also for the removal of foreign bodies and the diagnosis and treatment of small pathologic conditions or lesions such as carcinoma in situ in which the roentgenologic presentation is unclear. For this expansion of instrument use to be ensured, it is necessary to improve the resolution of the fiberoptic endoscope image and increase the instrument's angulation capabilities, increase the range of accessories that can be employed with it, and also increase familiarity with the instruments on the part of urologists.

Endoscopes↗

PubMed1988

[Citrate (CG-120) therapy for urolithiasis. 1. Clinical effects].

Urinary citrate is an important determinant for crystallization of calcium salts, and recently oral administration of citrate has been suggested to be clinically useful in the management of renal stone disease. The effect of CG-120, a citrate compound (potassium citrate, sodium citrate and citric acid) produced by Dr. Madaus (Germany), on upper urinary tract stones was investigated in 398 patients in this study group. The patients were treated with 3 or 4 g CG-120 daily. Two hundred thirty-one of them were treated accurately according to the protocol of the study for more than 32 weeks. The cumulative percentage of positive clinical effect for the stone (disappearance, passage or decrease in size) was 30.3% (70/231). There were no differences in the clinical effect between the group of 3 g/day and the group of 4 g/day. CG-120 seemed to be more effective in the cases of ureteral stone, young patients and females, but was less effective in the recurrent stone formers. Although there were 45 episodes of side effects in 38 patients in this study, no serious side effects attributed to CG-120 were experienced. CG-120 was proved as a useful drug in the treatment of upper urinary tract calculi as well as its prevention.

Adolescent↗

PubMed1988

[Citrate (CG-120) therapy in urolithiasis. 2. Effect on urinary and serum biochemistry ].

The long-term effects of citrate therapy (CG-120, 3 g/day or 4 g/day) were examined in 398 patients with upper urinary tract calculi. We studied the influence of citrate therapy on urinary and blood biochemistry in 353 of them. CG-120 caused a sustained increase in urinary citrate, urinary pH and potassium, but no substantial or significant changes in other urinary parameters (uric acid, phosphate, oxalate, sodium, chloride and urine volume). Although urinary calcium decreased significantly up to the 24th week, it did not change significantly there after and it tended to increase at the 54th week. Urinary creatinine excretion decreased after 34 weeks of administration, but this phenomenon could not be explained, because the level of blood urea nitrogen and serum creatinine was not elevated in any case before administration. There were no changes in the serum calcium, magnesium, phosphate, uric acid, sodium, potassium or chloride level.

Blood Chemical Analysis↗

PubMed1988

[Clinical study on the effect of CSF-HU (colony stimulating factor human urine) on leukopenia and granulocytopenia induced by cancer chemotherapy--a double-blind study in patients with genito-urinary cancer].

The ability of CSF-HU (P-100) to inhibit and improve the leukocytopenia and granulocytopenia which occur following cancer chemotherapy was investigated in a double-blind study which included an inactive placebo. The drug was administered, 2 vials/day (8 X 10(6)U of P-100), by intravenous drip infusion consecutively for 7 days starting from the 5th day after cancer chemotherapy was initiated. The total cases included in the study numbered 261. The efficacy rate was 53.0% for the P-100 group and 38.9% for the placebo group, while the usefulness rate was 54.8% for the former and 38.1% for the latter. In either case, statistically significant differences were observed in favor of the P-100 group. The reduction in the number of days before the leukocyte count returned to 4,000/mm3 was statistically significant in the P-100 group. While side effects appeared in both the P-100 (4.8%) and the placebo (4.4%) groups, none of them were considered to be serious. Judging from these results, p-100 was considered to be a useful therapeutic drug for the treatment of leukocytopenia and granulocytopenia following cancer chemotherapy.

Adolescent↗

PubMed1988

[Clinical studies on the measurement of urinary tissue polypeptide antigen (TPA) levels using Prolifigen TPA kit "Daiichi"-II in urothelial cancers].

We have investigated the clinical significance of urinary tissue polypeptide antigen (TPA) as a tumor marker for urothelial cancers. Urinary TPA levels were determined by the immunoradiometric assay of Prolifigen TPA Kit "Daiichi"-II in 486 healthy controls and 1835 patients with various diseases including 526 with urothelial cancers and 140 with prostatic cancer. The mean value of urinary TPA was 199 +/- 213 (1SD)U/1 in 486 healthy controls. 95% of them having a level below 600 U/l. Therefore, 600 U/l was applied as a cut-off level. Positive rates of urothelial cancers and reactivated prostatic cancer were 57.6% (148 of 248 cases) and 45.5% (5 of 11 cases) respectively. On the other hand, the false positive rate of most urological benign diseases was only about 20% except for the acute stage of urinary tract infections and upper urinary tract stones with hydronephrosis. There was no significant difference in the positive rate between urinary TPA level and urinary cytology in urothelial cancers. The combination of both tests raised the positive rate to 73.1%. Therefore, urinary TPA may be useful in the monitoring of urothelial cancers, and the combination of urinary TPA and urinary cytology may increase the diagnostic accuracy.

Antigens, Neoplasm↗

PubMed1988

[Collaborative study of UFT in far-advanced renal cell carcinoma. Urological Cooperative UFT Study Group].

A cooperative study of UFT was conducted in cases of far-advanced renal cell carcinoma. UFT was administered daily at a dose of 300-600 mg FT equivalent for at least 4 weeks. Forty-one patients were entered into the protocol from the 19 collaborating institutions in the group. The antitumor effects of the drug were clinically evaluable in 25 patients according to the response criteria proposed by the Koyama-Saito study group. Seven were not eligible and 9 were cases of protocol violation. Complete response (CR) and partial response (PR) were observed in 2 and 5 patients, respectively, showing a response rate of 28.0%. One patient showed minor response, 8 stable disease and 9 progressive disease. It took about 22 weeks and 16 weeks to attain CR and PR, respectively. Lung metastasis was the lesion showing most the favorable response to this treatment. Twenty-eight patients were used for evaluating the adverse effects of the drug. Gastrointestinal symptoms such as nausea, vomiting and anorexia, were observed most frequently, while bone marrow suppression was minimal. Only three patients had to be taken off the drug due to its adverse effects. In conclusion, UFT was considered to be one of the most effective drugs for the treatment of far-advanced renal cell carcinoma.

Adult↗

PubMed1988

[Efficacy of ofloxacin in sexually transmitted male urethritis and cervicitis].

Efficacy and safety of ofloxacin (OFLX), a new quinolone antibacterial agent, were investigated in cases of sexually transmitted male urethritis and cervicitis. Chlamydial infections occupied a large part of the patients enrolled. This study was conducted in 29 institutions. A total of 1,126 patients with gonococcal, chlamydial or non-gonococcal non-chlamydial infections were enrolled in the study. The general dosing regimen of oral OFLX was 100 mg t.i.d. or 200 mg t.i.d. for 14 consecutive days. Along with the clinical efficacy evaluated by doctors in charge, therapeutic and clinical efficacies were determined according to standardized evaluation criteria. The evaluation of therapeutic efficacy was based on bacterial eradication. On the other hand, clinical efficacy was determined upon the improvement in causative bacteria, WBC counts in smear (or initial urine) specimens and urethra/cervical discharges. Clinical efficacy was determined on 7 and 14 days after starting the medication, except for gonococcal infections for which the efficacy was determined on Day 3 and Day 7. The results obtained are summarized as follows. 1. Efficacy evaluation by standardized criteria Therapeutic efficacy rates in gonococcal infections were 97.9% (93/95) on Day 3 and 100% (119/119) on Day 7. In chlamydial infections, the rates were 77.7% (363/467) on Day 7 and 93.6% (392/419) on Day 14. Chlamydial urethritis rated 94.8% (239/252) and cervicitis 91.6% (153/167) on Day 14. Clinical efficacy rates in gonococcal infections were 63.2% (60/95) on Day 3 and 95.8% (114/119) on Day 7. In chlamydial infections, they were 70.0% (327/467) on Day 7 and 89.7% (376/419) on Day 14. Chlamydial urethritis rated 88.5% (223/252) and cervicitis 91.6% (153/167) on Day 14. Clinical efficacy rates in non-gonococcal non-chlamydial infections were 93.3% (97/104) for male urethritis and 65.9% (27/41) for cervicitis on Day 14. 2. Clinical efficacy determined by doctors in charge A total of 1,028 cases, 752 urethritis and 276 cervicitis cases, was evaluated by doctors in charge. Clinical efficacy rates were 90.3% for urethritis and 92.4% for cervicitis. 3. Safety Safety evaluations was conducted in 1,087 patients. Side effects were observed in 23 patients among them (2.12%). None of them were deemed serious. General laboratory examinations were conducted for 169 patients. Abnormal findings were seen in 11 patients (6.51%) or 13 cases, all of which were minor. The results of this multi-center clinical trial demonstrated that OFLX is effective and well tolerated in the treatment of sexually transmitted disease (STD), both gonococcal and chlamydial infections.

Adult↗