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Biomedical subjects

H Akaza

Publications and source records attributed to H Akaza.

At least 217 records · Page 12Linked to original sources
PubMed1991

[Superficial bladder cancer: prophylaxis of recurrence and progression].

Superficial bladder cancer has a good prognosis compared with invasive bladder cancer. However, recurrence of the tumor is frequent and tumor stage and/or grade progress at the time of recurrence in many cases. Intravesical chemotherapy has been employed as a prophylactic method after trans-urethral resection (TUR). Although intravesical chemotherapy has been proved to be effective in delaying the first recurrence of tumor after TUR, it cannot improve the ultimate prognosis of superficial bladder cancer. Many primary, solitary, non-invasive (Ta) and grade 1 tumors do not recur or progress in stage and grade. In these cases, prophylactic intravesical chemotherapy is not essential. Bacille Calmette-Guérin (BCG) should be considered superior overall, to any chemotherapeutic agents. Comparative studies will give information about the best clinical schedule for the treatment of superficial bladder cancer.

Administration, Intravesical↗
PubMed1991

[Comparative studies on the antitumor activity of fluorinated pyrimidine derivatives against human bladder, cervical and ovarian cancer xenografts in nude mice].

Fluorinated pyrimidines given orally were examined for their antitumor activity with 11 human cancer xenograft models (4 bladder, 4 cervical and 3 ovarian cancers). The drugs were evaluated to be effective when they inhibited tumor growth over 58%. UFT was not effective against all of 11 cancer xenografts tested. 5-Fluorouracil (5-FU) was effective against only one bladder cancer xenograft among 6 cancer xenografts tested. On the other hand, 5'-deoxy-5-fluorouridine (5'-DFUR) was effective against one bladder, 3 cervical and one ovarian cancer xenografts. The Antitumor activity of 5'-DFUR was correlated with the enzyme activity of pyrimidine nucleoside phosphorylase, which is an essential enzyme for phosphorolysis of 5'-DFUR to 5-FU.

Administration, Oral↗
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

Leuprorelin acetate depot: results of a multicentre Japanese trial. TAP-144-SR Study Group.

The clinical efficacy and safety of 3.75 or 7.5 mg leuprorelin acetate depot given subcutaneously once every 4 weeks was evaluated in a collaborative study of 81 patients with untreated prostatic cancer. Efficacy of treatment was assessed using criteria based on a meeting of the Prostatic Cancer Study Group funded by the Japanese Ministry of Health and Welfare and using National Prostatic Cancer Project criteria. Japanese criteria enabled evaluation of individual parameters, unlike the National Prostatic Cancer Project system which classified a patient as unevaluable if one evaluation parameter was unavailable. Leuprorelin acetate depot suppressed serum luteinizing hormone, follicle stimulating hormone and testosterone concentrations. Objective response rates of the prostate, bone metastases, serum prostatic acid phosphatase and soft tissue metastases, and subjective dysuria and pain responses were comparable to those found with conventional hormone therapy. Leuprorelin acetate depot was well tolerated, with no significant differences in response to the two doses.

Adult↗
PubMed1990

[Histological and flow cytometric analyses of carcinogenesis of rat prostate cancer].

Histological and flow cytometry (FCM) analyses were performed of carcinogenesis of rat prostate cancer induced with N-Nitroso-N-methylurea (NMU). Ten-week-old rats were inoculated intravenously (i.v.) with twice injections of NMU (30 mg/kg body weight) and then, divided into 3 groups; Group 1: the rats were injected subcutaneously with LH-RH analogue (100 micrograms/kg b.w.) every 4 weeks. Group 2: the rats were injected subcutaneously with testosterone enanthate (10 mg/body) every 2 weeks and Group 3: the rats were untreated to serve as controls. We further divided Groups 1 and 2 into (+) and (-) subgroups at 34 weeks after initial injection. Group 1 (+) or 2 (+) rats were continuously given the drug and in Group 1 (-) or 2 (-) rats the drug was suspended. At 44 or 53 weeks after initial injection, we removed the prostate and seminal vesicles of all rats and performed histological and FCM analyses of them. Histological analysis of rat prostates revealed hyperplasia in each group, and both Groups 2 (+) and 2 (-) showed an incidence as high as 87.5%. Atypical hyperplasia was sometimes observed in each group and its incidence was not significantly different between any 2 groups. At 51 weeks after initial injection, a macroscopic adenocarcinoma (weighing about 11 g) was found in the prostate of a dead rat of Group 2 (+). Histological analysis of rat seminal vesicles revealed hyperplasia in each group, in particular in Groups 2 (+) and 2 (-). In these groups all rats showed hyperplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Histological effects of endocrine therapy on prostatic cancer].

Histological effects of endocrine therapy were evaluated in one hundred and four prostatic cancer patients by new criteria presented by the committee of "General Rule for Clinical and Pathological Studies on Prostatic Cancer". Route and time of biopsy, clinical stage and histological grade were related to histological effects. Biopsy specimens taken within three months from the start of the therapy tended to score rather low marks and this tendency is especially apparent with low grade cancers. Histological effects evaluated by the present method correlated well with prognosis in localized stages (stage B, C and D1). In metastatic cases, however, local effects were not related to the prognosis.

Aged↗
PubMed1990

[Discriminant analysis of quantification theory on prognostic factors of chemotherapeutic effects on advanced testicular cancer. East Japan Testicular Tumor Study Group].

Prognostic factors of chemotherapy against advanced testicular cancer were analysed in 33 cases studied by East Japan Testicular Tumor Study Group. In this study a discriminant analysis of quantification theory (a multivariate analysis) was adapted, taking 7 factors as comparative variables. The significant factors for complete tumor response were clinical stage, histology, and tumor markers (HCG-beta, AFP). Prognostic score was calculated in each case by quantification theory, which correctly discriminated the group with CR from that without CR, at a probability of 90.1%. The results of our study indicate that the outcome of chemotherapy on advanced testicular cancer may be predicted with probability, by patients' status and adopted treatment. It may enable one to make an adequate treatment schedule for each patient.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

[Four cases of bladder replacement by enterocystoplasty after radical cystectomy for bladder cancer].

Four male patients with invasive bladder cancer, 44 to 68 years old in age, underwent bladder replacement with ileum after radical cystectomy. In three patients an ileal segment alone was isolated for construction of neobladder, and in the fourth patient, the terminal portion of the ileum, the cecum and the proximal part of the ascending colon were isolated for the bladder replacement. In all the cases isolated segments were detubularized for obtaining a low pressure reservoir. All the patients, except one who had a past history of cerebro-vascular disease and was performing intermittent self-catheterization because of a kind of detrusor-sphincter dyssynergia of the ileal-neobladder, are now enjoying almost the same voluntary urination as before the operation. Serum creatinine, BUN and electrolytes are all normal during the postoperative observation period, although a very slight metabolic acidosis was observed in 3 patients. Ten to 16 months have passed without any complications and all the patients are alive without any sign of tumor recurrence or metastatic involvement.

Aged↗
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↗
PubMed1990

Response criteria in research protocols for prostatic cancer.

This paper highlights some problems in the application of different response criteria for prostatic cancer and discusses what the most practical response criteria is. In this paper, we present some results of a multi-institution collaborative clinical study which employed response criteria developed by a Japanese study group (the Japanese Response Criteria for Prostatic Cancer; JRCPC) are reported. The JRCPC assesses response of a number of foci of disease independently, i.e., primary prostatic lesion, bone metastatic lesions and serum PAP level as well as bidimensionally measurable lesions. The overall response is evaluated on the basis of the response for each of the above parameters. In the present study, the serum PAP level was found to be, at present, the most sensitive parameter for predicting survival of patients with prostatic cancer. If the response is evaluated and recorded as a function of each parameter, as in the case of the JRCPC, it is relatively easy to re-evaluate the results using other criteria, thereby making it possible to compare the results with the results of other studies which employ different criteria. In the future, it will be important to improve the accuracy of measurement of the response of a variety of parameters specific for prostatic cancer in order to establish reliable response criteria to evaluate therapy.

Bone Neoplasms↗
PubMed1989

Phase II trial of carboplatin in patients with advanced germ-cell testicular tumors and transitional cell carcinomas of the urinary tract.

Carboplatin, an analog of cisplatin, was evaluated in a phase II study involving 25 patients with advanced testicular tumor and 45 with transitional cell carcinoma (TCC) of the urinary tract; 21 and 38 cases, respectively, were evaluable for response. Prior treatment with cisplatin-based chemotherapy had occurred in 7 of the testicular cancer patients and in 11 with TCC. The response rate (complete + partial response) in testicular tumors was 47.6%. The best response rate was observed in seminomas (70.0%), whereas the response rate in nonseminomas was 27.3%. The seminoma patients had mainly stage IIIA or less than IIIA disease, with metastatic lesions restricted to the lymph nodes. Three responses were seen in patients previously treated with cisplatin. In TCC, the response rate was 18.4%. Good-risk patients were treated with a dose of 400 mg/m2 every 4 weeks, whereas poor-risk patients received a lower dose of 300 mg/m2. The response rates for good-risk patients were 50.0% in testicular lesions and 26.1% in TCC. For poor-risk patients, the response rates were 40.0% and 6.7%, respectively. Carboplatin was well tolerated, with no significant renal impairment or ototoxicity detected. Nausea and vomiting were experienced by 51.7% of patients, but the severity was low; half of these patients demonstrated WHO grade I toxicity. However, myelosuppression was severe. In conclusion, carboplatin demonstrated activity in both testicular tumors and TCC and is worthy of further study, especially in combination with other active drugs.

Adult↗
PubMed1989

Expression of ras p21 oncogene product on human bladder tumors.

The immunohistochemical localization of ras p21 oncogene product was examined in human bladder cancer. These bladder cancers consist of 52 superficial bladder tumors and 10 cases of invasive tumor. Five (9.6%) of 52 superficial tumors were demonstrated to be positive for ras p21 product. Two (20%) of 10 cases which showed deep tumor infiltration were demonstrated to be positive for ras p21 oncogene product. When we analyzed the incidence of positive staining for ras p21 with regard to histological grade of bladder cancer, 2 of 30 (7%) patients with G1, 4 of 26 (15%) with G2, and 1 of 6 (17%) with G3 had positive staining for the ras p21 oncogene product. One of five patients who showed positive staining on tumors had tumor recurrence 3 months later. The remaining 4 patients positive for the ras p21 oncogene product had no tendency for recurrence in 11-19 months' follow-up. Therefore, the incidence of detection of ras p21 oncogene product on superficial and deep infiltrating bladder tumor was similar and there was no significant correlation between the incidence of positive ras p21 staining and depth of invasion of bladder tumors or histological grade.

Adult↗
PubMed1989

[Effects of LH-RH analogue on pituitary-testicular axis and bladder carcinogenesis of BBN administered male rats].

As a first step of investigating male predominance of bladder cancer incidence, we have studied relationships between rat bladder carcinogenesis, induced by BBN, and changes of pituitary-testicular axis, induced by a LH-RH analogue. The rats were divided into the following five groups. The first group (Age matched control group) was given normal drinking water for 30 weeks. The 2nd group (BBN group) was given a drinking water containing 0.05% BBN for 6 weeks. The 3rd group (LH-RH group) was given subcutaneous injections of a LH-RH analogue depot every four weeks. The 4th group (LH-RH + BBN group) was given subcutaneous injections of the LH-RH analogue depot every four weeks and a drinking water containing 0.05% BBN for 6 weeks. The 5th group (castration group) was castrated and given normal drinking water. The results were summarized as follows. 1) Serum LH, FSH and testosterone levels reached their peaks one day after the LH-RH analogue injection and decreased afterwards. Testosterone marked a castration level one week after the LH-RH analogue injection. 2) There was no significant difference between the BBN and non BBN groups in serum LH, FSH and testosterone levels. Thus, BBN did not influence the pituitary-testicular axis and the action of the LH-RH analogues. 3) Incidence of cancer was higher in the group of BBN + LH-RH than in the group of BBN 8 weeks after the start of the experiment. Then, the incidence was reversed between 20 weeks and 26 weeks; finally it became almost the same at 30 weeks. This phenomenon may be explained by the experimented schedule we applied; that is, BBN and LH-RH analogue were administered simultaneously. 4) Thus, changes of the pituitary-testicular axis induced by the LH-RH analogue seemed to have influence on bladder carcinogen.

Animals↗
PubMed1989

[Analyses of the effects of intravesical Bacillus Calmette-Guerin (Tokyo 172 strain) therapy of superficial bladder cancer].

In this paper, we summarize the results of a multicentric controlled study of induction treatment with intravesical BCG in patients with superficial bladder cancer (Ta, T1) or CIS. The BCG Tokyo 172 strain (Japan BCG K.K.) was given for 8 weeks, as a rule, in a dose of either 80 mg or 120 mg in 40 ml of saline instilled into the bladder. Sixty-six (90.5%) of the 73 patients registered in the study were evaluable for response. High response rates were obtained in the patients with Ta or T1 tumors, irrespective of the treatment dose; 65.4% CR, 27.3% PR and 7.3% NC for all. The number of CIS patients is too small to draw any conclusions, but 54.5% CR, 36.4% PR and 9.1% NC were obtained. Several factors were evaluated in relation to the tumor ablative effects. The CR rate was significantly higher for tumors less than 1 cm in size compared with tumors 1-3 or larger in size, although the response rates, including CR and PR, were very similar irrespective of the size. Other factors did not contribute to provoke a significant difference. Japanese elder people show a high positive rate of PPD reaction. Thus, in our study, 78% of the patients showed positive PPD reaction. In this situation, no significant relation between PPD reaction and BCG efficacy was obtained. In addition, OKT8, OKT7, OKT4, OKT4/OKT8 ratio, Leu7, ADCC activity and NK activity did not show any correlation with tumor ablative effect of BCG.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical↗