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Biomedical subjects

T Niijima

Publications and source records attributed to T Niijima.

At least 19 recordsLinked to original sources
PubMed1994

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.

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.

Administration, Intravesical↗
PubMed1992

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 for Adriamycin.

A multicentric randomised trial was conducted for the purpose of investigating the efficacy of intravesical chemoprophylaxis of superficial bladder cancers. 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 less than 0.05) on day 240, and those determined for groups A and C were also significantly different (P less than 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.

Administration, Intravesical↗
PubMed1992

Evaluation of systemic chemotherapy with methotrexate, vinblastine, adriamycin, and cisplatin for advanced bladder cancer. The Japanese Urological Cancer Research Group for Adriamycin.

In 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.

Adult↗
PubMed1992

[Ablative and prophylactic effects of BCG Tokyo 172 strain for intravesical treatment in patients with superficial bladder cancer and carcinoma in situ of the bladder. Bladder cancer BCG Study Group].

We investigated the effects of intravesical instillation of BCG Tokyo 172 strain on patients with superficial bladder cancer and CIS of the bladder for tumor ablation and prophylaxis. This is the first controlled multicenter study for governmental approval of BCG Tokyo 172 strain for the treatment of superficial bladder cancer and CIS of the bladder. One hundred-fifty-seven patients (125 with Ta or T1, and 32 with CIS) were treated by 80 mg of BCG diluted in 40 ml of saline, once a week for 8 weeks. The dose and interval adopted in this multicenter study was determined by the previous Phase II study conducted by the same Study Group. Out of 125 superficial tumor Ta, T1, 83 (66.4%) showed complete disappearance of the tumor (CR) and 26 (20.8%) partial disappearance (PR), and out of 32 CIS, 27 (84.4%) showed CR and 2 (6.3%) PR. Among those patients showing CR, and PR who were treated with additional TUR-Bt, 98 patients were randomised for a controlled study of prophylactic BCG instillation. Prophylactic treatment consisted of 40 mg of BCG diluted in 40 ml of saline, monthly for 12 months. Forty-two patients were assigned to the treatment group, whereas the remaining 56 to the control group without any prophylactic instillation. Three cases showed tumor recurrence during the prophylactic phase. Twenty-five cases could not be treated for the whole course of prophylactic instillation mainly due to bladder irritable symptoms. Recurrent free curves were compared till 1050 days after the initiation of the study. However, there was no significant difference between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical↗
PubMed1992

[Combination therapy with natural type human tumor necrosis factor (MHR-24) and human lymphoblastoid interferon-alpha (MOR-22) against renal cell carcinoma--a multiclinic cooperative, early phase II study. Subcommittee on Urogenital Malignancy, Committee on MHR-24 against Tumors].

The combination therapy with natural type human tumor necrosis factor (n-TNF; MHR-24) and human lymphoblastoid interferon-alpha (n-IFN-alpha; MOR-22) was investigated for antitumor effect against renal cell carcinoma in a multiclinic cooperative study throughout Japan. The "Response criteria of Japan Society for Cancer Therapy" were followed for the handling of subjects and the evaluation of antitumor effect. MHR-24 was administered at a daily dosage of 5,000-10,000 JRU by intravenous drip and MOR-22 at a dosage of 5,000,000 IU daily was administered intramuscularly at the same time. Both drugs were administered for 4 weeks or longer. A total of 36 patients were enrolled as subjects in the study. None of them were classified as ineligible. Five patients, were classified as imperfectly evaluable, and 31, as evaluable for the results of treatment. The responses in the evaluable patients were partial response (PR) in 4 patients, minor response (MR) in 3 patients, no change (NC) in 14 patients and progressive disease (PD) in 10 patients, with a response rate of 12.9%. Adverse reactions to the therapy were investigated in all 36 patients. The frequent subjective and objective reactions that occurred were fever, rigors and shivering, anorexia, and generalized malaise, and the frequent abnormal laboratory findings were leukopenia, thrombocytopenia, elevation of GOT, and elevation of GPT.

Aged↗
PubMed1992

Long-term clinical study on luteinising hormone-releasing hormone agonist depot formulation in the treatment of stage D prostatic cancer. The TAP-144-SR Study Group.

The results of long-term administration of leuprorelin acetate depot (TAP-144-SR), a sustained-release preparation of luteinising hormone-releasing hormone (LH-RH) agonist, to 40 stage D prostate cancer patients who had had no previous hormonal therapy, have been analyzed. The drug was administered by subcutaneous injection once every four weeks at a dose of 3.75 or 7.5 mg. The mean duration of treatment was 480 (141-1,266) days, and treatment continued for more than one year for 60% of the 40 patients. Objective response was evaluated in accordance with Japanese Response Criteria. The best objective response in the overall evaluation was a partial response in 68.6% of the total patient group (3.75 mg, 64.3%; 7.5 mg, 71.4%). During the administration period, 21 patients were diagnosed as having progressive disease (PD), and the mean time to onset of PD was 308 days. The earliest diagnoses of PD were made on bone metastases (17 cases) and prostatic acid phosphatase levels (12 cases). The survival rate, as determined by Kaplan-Meier's method, was 81.2% (3.75 mg, 80.5%; 7.5 mg, 81.3%) two years after starting the regimen and 66.0% (3.75 mg, 65.1%; 7.5 mg, 66.0%) after three years. There was no dose dependency between either of the two drug doses, which we adopted as functions of the objective response rate, and patients' survival. Serum levels of testosterone, LH and follicle-stimulating hormone (FSH) were monitored from the first-dose until the 148th week of administration. In all patients receiving the drug as scheduled, the testosterone level was maintained at less than 1 ng/ml, and the LH and FSH levels were maintained at levels lower than their respective upper normal limits. There were no particular adverse reactions specific to the long-term administration subsequent to the foregoing 12-week administration study. In conclusion, LH-RH analogue treatment is thought to be a long-lasting, effective, palliative measure for patients with previously-untreated, advanced, prostatic cancer.

Aged↗
PubMed1991

[Clinical study of RU 23908 (nilutamide) in prostatic cancer].

To investigate the efficacy and the safety of RU23908 for the treatment of prostatic cancer, an early phase 2 study with the oral administration of 150 or 300 mg daily was performed in 47 patients with stage C or D prostatic cancer at 15 institutions from April 1987 to June 1988. Forty patients were evaluable for efficacy. Concerning the effect on the object lesion, the results of the overall evaluation revealed that complete or partial response (CR + PR) was obtained in 34 of the 40 cases (85.0%). As to the effect classified by site, CR + PR were observed in 35 out of the 40 cases with primary lesion (87.5%), in 10 of the 22 cases with bone metastasis (45.5%), in 5 of the 6 cases with lymph node metastasis (83.3%) and CR was observed in one case with lung metastasis. In the PAP evaluation, 33 out of the 34 cases were judged to be CR + PR (97.1%). The improvement rate of clinical symptoms was 88.9% for bone pain, 83.3% for dysuria and 45.5% for performance status. Adverse reactions were observed in 29 of the 47 cases (61.7%) investigated and 7 cases (14.9%) were withdrawn. During the study period of 12 weeks and the subsequent period of continued administration, 6 cases (12.8%) and 2 possible cases of interstitial pneumonia were diagnosed. From the above results, the treatment of prostatic cancer with RU23908 150 mg/day or 300 mg/day in combination with surgical castration showed an excellent clinical effect compared to conventional endocrine therapy, but has a problem of safety. Therefore, this drug may be expected to be a highly useful therapeutic drug, if safely is improved in the future by reviewing the dose.

Administration, Oral↗
PubMed1991

[Clinical phase III study on TAP-144-SR, an LH-RH agonist depot formulation, in patients with prostatic cancer].

A randomized controlled phase III clinical trial comparing TAP-144-SR (TAP) and diethylstilbestrol diphosphate was conducted for patients with prostatic cancer. Patients with Stage B, C, or D disease, who were previously untreated, were enrolled. TAP-144-SR 3.75 mg was administered subcutaneously at 4-week intervals for 12 weeks (a total of 3 injections) in the TAP-144-SR group, while 100 mg of diethylstilbestrol diphosphate was administered orally three times a day (before meals) for 12 weeks in the control group. A total of 141 patients were enrolled using a centralized telephone registration system. Four of these patients were ineligible, and there were 3 drop-outs who never received drugs because they withdrew their consents to participate in the trial. These 7 were excluded from the evaluation, and as a result, 134 patients (66 in the TAP group and 68 in the control group) were evaluable in safety and efficacy. Between the two groups, there were no significant differences in patient characteristics, except the age distribution. Clinical response rates (CR+PR) in evaluable patients according to the criteria of Japanese Prostatic Cancer Study Group were 54.5% in the TAP group and 47.1% in the control group. In addition, the rates according to the criteria for Evaluating the Direct Response to Chemotherapy in Solid Carcinomas and NPCP criteria were 7.6% in the TAP group and 8.8% in the control group and 18.2% in the TAP group and 20.6% in the control group, respectively. Using any of the three criteria, there were no significant differences in response rate between the two groups. The incidence of side effects was 64.1% in the TAP group and 95.4% in the control group; the incidence being significantly higher in the control group (p less than 0.001; chi 2-test). Therefore, the overall safety was significantly greater in the TAP group than in the control group (p less than 0.001; chi 2-test). On the basis of the efficacy and safety the clinical usefulness rate of TAP-144-SR was significantly higher than that of diethylstilbestrol diphosphate (p = 0.038; U-test). In conclusion, TAP-144-SR was confirmed to be more useful than diethylstilbestrol diphosphate as a standard drug for hormonal therapy of prostatic cancer.

Aged↗
PubMed1990

Cooperative study of pirarubicin against urological cancers and future direction of its combination use. The Clinical Study Group of THP for Urological Malignant Tumors.

In the urological field, one of the most effective drugs is doxorubicin. A cooperative phase II study on pirarubicin (THP), a new anthracycline with less cardiotoxicity than doxorubicin, was performed in 14 institutions for treating urological tumors. THP was administered intravenously 3 or more times (as one course, 30-40 mg/m2 once a week, every 3 weeks or 20 mg/m2 2 consecutive days a week every 3 weeks). Fifty-four of the 63 patients included in this study were evaluable. An overall efficacy rate was 18.5% (10/54), consisting of transitional cell carcinoma 24.3% (9/37; bladder cancer 6/27 (22.2%), tumors of the renal pelvis and ureter 3/10 (30.0%), and prostatic cancer 1/15 (6.7%). Adverse effects were mostly slight especially alopecia (15.9%, WHO grade 1:7 patients and grade 2:3 patients), and there was no problem attributable to cardiotoxicity of THP. Leukocytopenia was seen for 65.1% (grade 1:14 patients, grade 2:13 patients, grade 3:13 patients, and grade 4:1 patients). The nadir was observed about 2 weeks later and it took about 2 weeks for the recovery. Thus, it can be concluded that the usefulness of THP in treating urological tumors is comparable to or better than that reported for doxorubicin. Based on the above results, a combination regimen including THP has been investigated in Japan.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

[Clinical phase I and phase II study on a sustained release formulation of leuprorelin acetate (TAP-144-SR), an LH-RH agonist, in patients with prostatic carcinoma. Collaborative++ Studies on Prostatic Carcinoma by the Study Group for TAP-144-SR].

TAP-144-SR is a sustained release formulation of an LH-RH agonist, leuprorelin acetate (TAP-144), that has been newly developed in Japan. As a phase I study, a single subcutaneous dose of TAP-144-SR was given to 15 patients with prostatic cancer to investigate the safety, endocrinological effects, and serum levels of the drug. The patients were divided into four groups according to the dosage levels of 1.88 mg, 3.75mg, 7.5 mg and 15 mg. No serious side effects were noted in any of the patients treated with any dose. No patients exhibited signs of a local reaction at the site of injection. In two patients transient exacerbation of clinical symptoms owing to "flare up" was observed. Serum testosterone levels decreased to the castration level (less than 1.0 ng/ml) in all of the patients, although the time required to attain the castration level tended to be longer in the patients receiving 1.88 mg. Serum TAP-144 levels increased on the first day and gradually decreased thereafter. In the groups of patients that received 3.75 mg or more of TAP-144-SR, TAP-144 was detected in the serum up to 4 weeks after administration. Based on the results of the phase I study, 3.75 mg and 7.5 mg of TAP-144-SR were selected as the doses for the phase II study. The phase II study was carried out as a multi-center open trial. Patients with stage B-D prostatic cancer received subcutaneously either 3.75 mg (3.75 mg group) or 7.5 mg (7.5 mg group) of TAP-144-SR once every 4 weeks for a total of 3 doses over a period of 12 weeks. TAP-144-SR 3.75 mg was administered to 51 patients and 7.5 mg to 50 patients. Both of these doses were adequate to suppress serum LH and FSH levels. Serum testosterone was decreased to the castration level within 22 days after the first dose, and this suppression was maintained throughout the treatment period. Clinical response rate (CR + PR) was 21% in the 3.75 mg group and 22-24% in the 7.5 mg group according to the Criteria for Evaluating the Direct Response to Chemotherapy in Solid Carcinomas and NPCP criteria. The response rate by the criteria of Japanese Prostatic Cancer Study Group was 51% in the 3.75 mg group and 62% in the 7.5 mg group. Adverse reactions were noted in 26% of patients in the 3.75 mg group and 34% in the 7.5 mg group.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1989

Intravesical treatment of bladder cancer with recombinant human interferon-beta. Intravesical GKT-beta Chemotherapy Research Group.

In order to examine its clinical efficacy, recombinant human interferon-beta (rIFN-beta) was instilled intravesically into 51 patients with superficial bladder cancer. Ten patients, who received intermittent intravesical instillation at a dose of (3-36) x 10(6) U rIFN-beta on days 1-3 every week, showed no response. Thirty-two patients received intravesical instillation at a dose of (3-36) x 10(6) U every day for 10-20 days. Eight patients showed partial response, indicating an efficacy rate of 25%. Nine patients received divided doses of 18 x 10(6) U twice a day every day for 10-20 days. Six patients showed partial response, indicating an efficacy rate of 67%. This value was significantly higher than that obtained by administering divided doses. The response to intravesical instillation therapy with rIFN-beta varies with treatment protocol. Frequent and longer exposure to rIFN-beta may induce better regression of superficial bladder cancer. Six incidences of side-effects were found in five cases (9.8%): pollakiuria in one, pain on micturition in two, fever in two, and eruption in one case. All of these side-effects were slight and reversible after drug withdrawal. Laboratory tests showed only a few changes with low severity. Thus, rIFN-beta is potentially a new drug for instillation therapy of superficial bladder cancer, in view of the absence of adverse effects.

Adult↗
PubMed1989

Renal hypercalciuria and acidification defect in kidney stone patients.

Calcium metabolism and renal acidification ability were examined in renal stone patients. On a random diet 33 of 52 patients excreted more than 4 mg. per kg. body weight per day of urinary calcium and were entered into a second study on a 300 mg. calcium diet. Absorptive and renal hypercalciuria was differentiated by fasting urinary calcium (mg. per 100 ml. glomerular filtration). Every absorptive hypercalciuria patient tested and 5 renal hypercalciuria patients had a normal renal acidification ability, and the serum parathyroid hormone and urinary cyclic adenosine monophosphate levels were normal. By calcium restriction urinary calcium decreased more in absorptive hypercalciuria than in renal hypercalciuria (2.48 +/- 0.14 versus 3.34 +/- 0.27 mg. per kg. body weight per day, p less than 0.05). However, urinary calcium remained high in 76 per cent of the patients with absorptive hypercalciuria. Nine patients had a defect in renal tubular acidification and the calcium metabolism was similar to those with renal hypercalciuria. Present studies show that renal hypercalciuria and renal tubular acidification defect cannot be differentiated without an ammonium chloride test.

Acidosis, Renal Tubular↗
PubMed1988

Renal hypercalciuria and metabolic acidosis associated with medullary sponge kidney: effect of alkali therapy.

Sixteen patients with medullary sponge kidney (MSK) and renal stones underwent evaluation of calcium metabolism and acid base balance. Six normal subjects and eight patients with non-MSK absorptive hypercalciuria served as control. Nine (56%) were hypercalciuric and seven (44%) were normocalciuric (N-MSK). Hypercalciuria was divided into absorptive (AH-MSK, n = 2) and renal leak hyerpcalciuria (RH-MSK, n = 7). The mean of minimal urine pH of RH-MSK group (5.28 +/- 0.09 (SE] was significantly higher than that of normal control (4.78 +/- 0.12) and of non-MSK AH (4.80 +/- 0.6) during acute acid challenge. The mean of the arterial blood HCO3 concentration of RH-MSK group was significantly lower than that of two control groups. The urine calcium and a frequency of stone passage were decreased significantly after alkali treatment in RH-MSK.

Acid-Base Equilibrium↗
PubMed1988

Medullary sponge kidney and hyperparathyroidism.

Medullary sponge kidney (MSK), parathyroid adenoma, renal cell carcinoma, and renal-leak hypercalciuria coincided in 1 female patient. Renal-leak hypercalciuria was not corrected by removal of a parathyroid adenoma. Since the patient had renal tubular acidosis (RTA), alkali treatment was conducted and resulted in the correction of hypercalciuria. Renal cell carcinoma eventually developed and MSK was confirmed histologically. This case suggests that MSK and primary hyperparathyroidism occurred independently.

Calcium↗