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Biomedical subjects

H Akaza

Publications and source records attributed to H Akaza.

At least 145 records · Page 8Linked to original sources
PubMed1996

[Phase I study of bicalutamide (Casodex), a nonsteroidal antiandrogen in patients with prostatic cancer].

A phase I study (open trial) of bicalutamide (Casodex), a non-steroidal antiandrogen, was conducted on 16 patients with prostatic cancer (stage C to D). The patients were given 10, 30, 50, 80 or 100 mg of bicalutamide orally daily for 12 weeks. Adverse reactions were observed in 8 out of 16 patients, but almost all were mild. Breast pain, gynecomastia and hot flushes were observed in 6 patients. Adverse reactions regarding liver function tests were observed in 3 patients. These were increased glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), alkaliphosphatase (AL-P) or gamma guanosine 5'-triphosphate (gamma-GTP). However, during or after the treatment period the elevated values were reversed to the pretreatment level. In terms of efficacy, anti-tumor effect was observed in 1 or 2 patients at each dose. Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol increased during treatment. Plasma concentrations of the R (-) enantiomer, which has antiandrogenic activity, reached the steady state 6-8 weeks after the initiation of treatment; its apparent plasma elimination half-life observed following repeated administration was 8.4 +/- 1.1 days. In conclusion, bicalutamide (10-100 mg od) is considered to be tolerated well enough to be administered to patients with prostatic cancer and has shown evidence of anti-tumor effect.

Administration, Oral↗
PubMed1996

[Clinical early phase II study of bicalutamide (Casodex) in patients with prostatic cancer].

To investigate the efficacy and safety of bicalutamide (Casodex) with its clinically recommended dose, the randomized early phase II study was performed in 124 patients with prostatic cancer (stage C, D). The patients were given 50, 80 or 100 mg of bicalutamide orally once a day in fixed doses for 12 weeks; 122 patients were eligible for evaluation. The overall response rate was 50.0% (20/40), 61.0% (25/41) and 53.7% (22/41) in the 50 mg, 80 mg and 100 mg groups, respectively. The response rate in prostate lesion, bone and lymph node metastases was slightly higher in the 80 mg group than in the 50 mg and 100 mg groups. The proportion of patients showing a response with regard to serum PSA (CR and PR) was 84.2, 92.7 and 97.6% in the 50, 80 and 100 mg groups, respectively. The incidence of adverse reactions was 65.0, 61.0 and 61.0% in the 50, 80 and 100 mg groups, respectively, and there was no significant difference in overall safety rating in the three groups. Frequent adverse reactions were gynecomastia and breast pain. Only one patient in the 80 mg group was withdrawn due to shortness of breath. Serum concentrations of LH, testosterone and estradiol increased significantly after treatment. Bicalutamide was concluded to be effective and well tolerated in patients with prostatic cancer, and its recommended dose was 80 mg once daily.

Administration, Oral↗
PubMed1996

[Salvage therapy for refractory testicular cancer].

Cisplatin-based conventional chemotherapy followed by surgery can cure 80-70% of disseminated testicular cancers. Effective salvage therapy is required for the remaining 20-30% of patients. High-dose chemotherapy (HDCT) combined with autologous stem-cell rescue for refractory testicular tumor results in about 10-20% durable complete responses. Hematologic toxicity is severe, and about 10% treatment-related deaths were reported in early investigations. Early salvage therapy or first-line therapy using HDCT is under investigation to improve treatment efficacy of the refractory or poor-risk testicular cancer. One of the important findings of these trials is that a platinum analogue may be critical to HDCT for cisplatin-refractory cases. Recent basic research has showed that platinum-containing anticancer drug provokes a complex response in the cancer cells. It is hoped that investigation of the mechanism of cisplatin-resistance or development of a new platinum complex will overcome the limitations of salvage chemotherapy for this disease. Finally, several investigators reported that highly selected chemorefractory patients, even with positive tumor markers, have definite potential for cure with surgical resection of localized metastatic disease. Thus, salvage surgery may be indicated for patients refractory to all potentially curative chemotherapeutic regimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[Analysis of site differences in voiding condition of elderly men-- comparison to results of mass screening for prostate diseases between the villages of Shimamaki-mura, Hokkaido and Satomi-Mura, Ibaraki].

We performed mass screening for prostate diseases in the village of Satomi-mura, in Ibaraki Prefecture for males between 40 and 79 years old (participation rate; 21%). The findings were compared to those obtained by mass screening in the village of Shimamaki-mura, in Hokkaido Prefecture, conducted by the same examiners in a consistent manner (participation rate; 47%). When we considered the difference in biopsy rates between the two sites, the detection rate of prostate cancer in Satomi-mura was similar to that in Shimamaki-mura. There were no apparent differences in distribution of prostate volume, the International Prostate Symptom Score (I-PSS) and maximum flow rate between the two sites for each 10-year-age group. Our findings suggested that there was little site difference in the detection rate of prostate cancer and voiding condition between the two villages.

Adult↗
PubMed1996

[The role of etoposide therapy in urogenital cancer].

Testicular cancer is recognized as a model of curable cancer by chemotherapy, and etoposide is the one of the most important drugs in its treatment. Etoposide has been used with cisplatin and bleomycin as a first-line combination chemotherapy since the early 1980s. It is now the key drug in the setting of high-dose chemotherapy for refractory cases. Oral, low-dose etoposide may provide effective palliation in some patients refractory to possible curative salvage therapy. Oral etoposide may also play a role in the maintenance therapy adjunctive to salvage therapy. Nevertheless, etoposide has failed to show definite therapeutic efficacy in the treatment of renal cell carcinoma and bladder cancer. The combination therapy of oral etoposide and estramustine, however, showed promising results for the treatment of hormone-refractory prostate cancer. Further investigations are required for this new treatment strategy for prostatic cancer.

Antineoplastic Agents, Phytogenic↗
PubMed1995

Bacillus Calmette-Guérin treatment of existing papillary bladder cancer and carcinoma in situ of the bladder. Four-year results. The Bladder Cancer BCG Study Group.

BACKGROUND: Intravesical instillation therapy of Bacillus Calmette-Guérin (BCG) has become a standard treatment for carcinoma in situ (CIS) of the urinary bladder. However, there have been few reports concerning the direct effect of BCG on existing tumors classified as Ta or T1. In the first stage of this clinical study, 157 patients were treated with BCG intravesical instillation (Tokyo 172 strain [BCG Co. Ltd., Tokyo, Japan]; 80 mg weekly for eight times) by our Study Group. The efficacy on existing tumors was a complete response (CR) rate of 84.4% and 66.4% and a partial response (PR) of 6.3% and 20.8% for 32 cases of CIS and 125 cases of Ta or T1 tumors, respectively. METHODS: In the second stage of this study, the authors investigated the outcome of the 138 patients who had achieved CR or PR in the first stage. One hundred twenty (87.0%) of the patients were followed fully. Of those patients, 52 were randomized to receive prophylactic (maintenance) therapy consisting of BCG of 40 mg monthly for 12 times (Group A), whereas 55 were randomized to an untreated control group (Group B). Thirteen other patients refused to be randomized and were followed without prophylactic instillation. RESULTS: The median follow-up period was 48 months for Group A and 42 months for Group B. In Groups A and B, the beneficial effect of the BCG therapeutic instillation persisted for a long time, and the 3-year nonrecurrence rate was 77.6% in Group A and 74.2% in Group B. Disease progression was observed rarely. CONCLUSION: For patients in whom transurethral resection of tumors of the bladder (TUR-Bt) alone is unlikely to eliminate the tumor, intravesical BCG is potentially the treatment of choice.

Administration, Intravesical↗
PubMed1995

Proliferating cell nuclear antigen cyclin in human transitional cell carcinoma.

OBJECTIVES: To confirm the value of the proliferating cell nuclear antigen (PCNA) labelling index in relation to histological grade, stage and prognosis. MATERIALS AND METHODS: Tissue specimens from 56 patients (49 men, 7 women; mean age 65 years [range 34-86]) with newly diagnosed transitional cell carcinoma of the urinary bladder were stained by an avidin-biotin peroxidase method using an anti-PCNA monoclonal antibody. Immunohistochemical analysis was performed on ethanol-fixed, paraffin-embedded tissue sections obtained by endoscopic biopsy or transurethral resection (TUR). The PCNA labelling index was determined by counting the number of PCNA-labelled cells in the tissue sections. RESULTS: Grade 1 tumours averaged 5.1 +/- 3.0% labelling versus 10.9 +/- 5.2% in grade 2 tumours, and grade 3 tumours had a PCNA labelling index of 21.8 +/- 10.4%. The average labelling indices for superficial tumour (37 patients) and invasive tumour (19 patients) were 7.5 +/- 5.3% and 20.8 +/- 10.0%, respectively. A distant metastatic bladder tumour showed an average labelling index of 42.3%. To analyse survival, tumours with PCNA indices above and below the median level (12%) were compared. Those patients with an index of < 12% (the mean of all of the PCNA values) had a worse prognosis than those with an index of > 12%. The mean PCNA labelling indices in recurrent and non-recurrent tumours were 6.4 +/- 0.7% and 8.2 +/- 1.7%, respectively, statistically not significant. CONCLUSION: The higher PCNA labelling index may indicate biological malignancy. These results suggest that measurement of the PCNA labelling index in bladder cancer may prove to be an objective and quantitative assay of biological aggressiveness and provide significant prognostic information, though it does not help to select patients at high risk of recurrence in superficial tumours.

Adult↗
PubMed1995

The importance of dose intensity in chemotherapy of advanced testicular cancer.

PVB regimen, the combination of cisplatin (CDDP), vinblastine (VLB) and bleomycin (BLM), has improved the treatment results of testicular cancer patients. However, modification of doses and schedules were strongly related with the treatment results. We analyzed the relative dose intensity (RDI) of each patient undergoing PVB regimen, in relation to the chemotherapeutic effect. In addition, a role of granulocyte colony-stimulating factor (G-CSF) on dose intensity of PVB regimen was analyzed. During the period 1981-1992, 33 patients with testicular cancer were treated with PVB regimen. Among the 25 evaluable patients, 5 (20%) achieved a complete response (CR), 15 (60%) had a partial response (PR), and the overall response rate was 80%. The average 5-year survival rate of all cases was 78.4%. The RDI in CR and PR cases were significantly higher than nonresponders in BLM (0.89 for CR and 0.91 for PR against 0.32 for NC + PD) in the combination of the three drugs (1.05 for CR and 0.97 for PR against 0.69 for NC + PD). The standard-dose group (RDI > or = 0.9) had a higher survival rate than the modified-dose group (RDI < 0.9). The RDI of PVB regimen with administration of G-CSF was 0.98, whereas in the PVB-alone group it was 0.87 (p < 0.01). Our findings indicate that the RDI of BLM may be one of the most important factors in achieving a chemotherapeutic effect from the PVB regimen. G-CSF is useful for the completion of the schedule through the increase in dose intensification, and the prevention of leukocytopenia due to chemotherapy.

Adolescent↗
PubMed1995

Preventive effect of a Lactobacillus casei preparation on the recurrence of superficial bladder cancer in a double-blind trial. The BLP Study Group.

A double-blind trial was conducted in 138 patients with superficial transitional cell carcinoma of the bladder following transurethral resection to evaluate the prophylaxis of recurrence by an oral Lactobacillus casei preparation (BLP). Patients were stratified into the following 3 subgroups: (A) with primary multiple tumors; (B) with recurrent single tumors, and (C) with recurrent multiple tumors. In each group, patients were randomly allocated to receive BLP or placebo. BLP showed a better prophylactic effect in subgroups A and B than placebo, whereas no significant difference was observed in subgroup C. Cox multivariate analysis showed that the outcome with BLP was significantly better than with placebo (p = 0.01). Slight and tolerable adverse reactions occurred in 3 patients receiving BLP and in 3 of the placebo-treated patients. Oral administration of BLP was thus safe and effective for preventing recurrence of superficial bladder cancer.

Administration, Oral↗
PubMed1995

BCG treatment of existing Ta, T1 tumours or carcinoma in situ of the bladder.

There are theoretical limits to the efficacy of intravesical instillation of anticancer agents as a method to prevent recurrence of superficial bladder cancer. Studies on the direct efficacy of intravesical instillation of bacillus Calmette-Guérin (BCG) to treat existing papillary tumours (Ta, T1) have shown a complete response rate of 66.4% and a partial response rate of 20.8%. These figures represent potent efficacy similar to that of BCG in the treatment of carcinoma in situ (CIS). Moreover, this efficacy was found to persist over a long period of time, and the subsequent recurrence rate was markedly reduced. In cases with multiple tumours, or in subjects where concurrent CIS is strongly suspected, these findings suggest that intravesical instillation of BCG might best be performed prior to transurethral resection of bladder tumours.

Administration, Intravesical↗
PubMed1995

[A case of urinary ascites probably caused by spontaneous bladder rupture].

The patient was a 68-year-old woman, who had underwent radical hysterectomy and postoperative radiation therapy thirteen years ago, and suffered from typical symptoms of panperitonitis in 1992 and 1993. Based upon laboratory findings of ascites, intraperitoneal urinary extravasation was suspected as the cause of panperitonitis. However, IVP, cystography, cystoscopy could not show the direct evidence of extravasation. On urodynamic study, poor flow rate, large postvoided residual urine, disturbance of the bladder sensation, and low compliance were present. We considered the neurogenic bladder dysfunction and detrusor weakness due to the previous radical hysterectomy and radiation therapy as the possible causal factors of spontaneous bladder rupture causing urinary extravasation from the bladder in this case.

Aged↗
PubMed1995

[alpha-Interferon therapy in a patient with renal cell carcinoma and renal hypofunction].

A 60-year-old man who had renal cell carcinoma with renal hypofunction underwent partial nephrectomy followed by alpha-interferon therapy (LHBI 3 x 10(6) IU/day intramuscular injection for 4 weeks, then twice a week for 6 months). Glomerular filtration rate slightly decreased to 28. 5 from 32.6 ml/m after partial nephrectomy. On single injection of IFN, its serum level reached the maximum of 20.3 IU/ml, at 12 hours of injection, and 10.4 IU/ml at 24 hours. After 4 weeks, that was 50.6 IU/ml. NK activity and ADCC which were 32, and 68%, respectively before treatment, reduced to 6, and 28%, respectively after 4 weeks. After maintenance therapy they were shown to rise up to 26, and respectively 73%, and increased immunoactivity was confirmed.

Carcinoma, Renal Cell↗
PubMed1995

[Effects of androgen regulation system on bladder carcinogenesis in male mice].

PURPOSE: In several previous reports, it has been suggested that the androgen system is related to bladder carcinogenesis. In this study, to understand the mechanism underlying this relationship, we administered a LH-RH agonist depot (Leuprolide depot), a pure-antiandrogen (flutamide) or a 5 alpha-reductase inhibitor (finasteride) to the mice in the promotion state of bladder carcinogenesis by N-butul-N-(4-hydroxybutyl) nitrosamine (BBN). MATERIALS AND METHODS: 177 C3H/He male mice were divided into 7 groups. All mice were treated with 0.05% BBN for 10 weeks and were maintained over the subsequent 12 weeks with the following treatments. Group 1 was a control group; in group 2, castration was performed at the 11th week; in group 3, finasteride was administered starting the 11th week; in group 4, a LH-RH agonist depot was administered starting the 11th week; in group 5, flutamide was administered starting the 11th week; in group 6, both finasteride and a LH-RH agonist depot were administered simultaneously starting the 11th week; and in group 7, both flutamide and a LH-RH agonist depot were administered simultaneously starting the 11th week. RESULTS AND CONCLUSIONS: (1) We confirmed that castration significantly suppressed bladder carcinogenesis. (2) Finasteride or flutamide administration as monotherapy had no effect on the results; however, the dosages of these drugs may have been too low, so we are planning a study with higher doses. (3) Conversely, the LH-RH agonist depot significantly promoted bladder carcinogenesis, we believe that the high levels of testosterone immediately after the administration were responsible for this promotion. (4) Simultaneous administration of flutamide suppressed this LH-RH induced promotion of carcinogenesis.

5-alpha Reductase Inhibitors↗
PubMed1995

[The squash technique for silver staining of argyrophilic nucleolar organizer regions on bladder tumors: comparison with paraffin embedded sections].

We examined nucleolar organizer region (NOR) indices on 13 bladder tumors on both squash-prepared specimens and paraffin embedded specimens stained by silver-colloid method. It was noted that; 1. The nuclear size was enlarged by squashing, 2. Aggregated NOR dots were dispersed, 3. Uniformity of microscopic phase of the dots was obtained, 4. Squash specimens had more precise countabilities than the paraffin embedded sections for avoidance of nuclear resection. NOR indices (mean +/- S.D.) of those bladder tumors on squash-preparation and paraffin section were 8.64 +/- 4.32 and 6.13 +/- 1.58, respectively, and the former showed good correlation with the tumor stage. When we prepare the squashed specimen from the surgically resected bladder tumor tissue, embedding and sectioning processes which are inevitable for preparation of paraffin embedded section, could be eliminated. Thus, squash-smear technique was considered to be better than the method using paraffin embedded section on the point of shorter duration of examination and accurate countability of the NOR dots.

Aged↗
PubMed1995

[Preoperative chemotherapy in genitourinary cancer].

Preoperative chemotherapy is the standard therapy for metastatic testicular cancer, and is also a candidate for a new treatment modality in management of bladder cancer. Since the advent of cisplatin-based chemotherapy in the late 1970s, a majority of metastatic testicular cancer patients can be made disease-free and cured with chemotherapy followed by surgery. The development of combination chemotherapy including cisplatin and methotrexate in the late 1980s also improved the tumor regression rate for bladder cancer. However, the chemotherapy for the metastatic bladder cancer can not control a relapse after initial response, nor improve the survival rate, significantly. While several pilot studies suggest that the neoadjuvant chemotherapy may be beneficial in non-metastatic invasive bladder cancer, the results of randomized trials are presently not available to define the role of this new treatment modality in management of bladder cancer. Intra-arterial chemotherapy combined with radiotherapy and conservative surgery may be indicated for selected patients as bladder preservation therapy.

Chemotherapy, Adjuvant↗
PubMed1995

[Improvement of survival of testicular cancer patients through chemotherapy].

Because treatment of testicular cancer has improved dramatically during the past 15 years, about 70% of the patients can be relieved of this disease today. Although this can be attributed to the availability of various tumor markers, better imaging diagnosis and improvement of surgical techniques, the improvement of chemotherapy, mainly based on cisplatin, has made the largest contribution. Hopefully, more powerful chemotherapy regimens will be available for patients who fail to respond to primary chemotherapy or relapse within a short period after primary chemotherapy. Supportive therapy, such as bone marrow transplantation, will serve to enhance the treatment for testicular cancer. On the other hand, milder therapy will given, if it is determined sufficient to treat the patient with an excellent response to the present therapeutic regimen. In the future, more therapeutic regimens will be prescribed to meet the exact needs of individual patients according to their prognoses.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Chlormadinone acetate withdrawal syndrome under combined androgen blockade for advanced prostate cancer.

Between July 1991 and December 1994 at Tsukuba Gakuen Hospital, we treated 19 consecutive men with advanced adenocarcinoma of the prostate (five at stage C, four at stage D1 and 10 at stage D2). Of these, 14 patients underwent castration (two patients) or received LH-RH analogue (12 patients) plus chlormadinone acetate for combined androgen blockade. We report three representative cases of sequential prostate specific antigen (PSA) elevation following initial response to this combined androgen blockade. Discontinuation of chlormadinone acetate resulted in decline of the serum PSA level. This suggests that trial chlormadinone acetate withdrawal in patients showing increasing levels of PSA during combined androgen blockade should be considered before initiation of alternative treatment.

Adenocarcinoma↗