Search PubMed⌕ Search

Biomedical subjects

H Akaza

Publications and source records attributed to H Akaza.

At least 235 records · Page 13Linked to original sources

Comparative investigation on use of (2''R)-4'-O-tetrahydropyranyl-adriamycin and adriamycin as intravesical chemotherapy for superficial bladder tumors.

An intravesical chemotherapeutic agent must be capable of being rapidly absorbed by the tumor cells and expressing its activity while undergoing little systemic absorption. A comparative investigation was conducted on (2''R)-4'-O-tetrahydropyranyl-doxorubicin (Adriamycin) (THP) and Adriamycin (ADM) from the above viewpoint using cultured MBT-2 and T-24 cell lines. From in vitro experimental systems, it is surmized that THP is taken up by bladder tumor cells more rapidly than ADM is, and that THP is thus able to exert its effect on the bladder tumor within a shorter time than that required by ADM. This pharmacokinetic advantage of THP was proved in an in vivo experimental system; that is, bladder tumor tissue which was established by implanting MBT-2 cells into the mouse (C3H/He) bladder was found to contain THP in a concentration approximately 1.9 times higher than the concentration of ADM. The amount of systemic absorption from the bladder was small in the case of both THP and ADM. THP should be useful as a new agent for intravesical chemotherapy.

Administration, Topical↗

LH-RH agonist, Zoladex (Goserelin), depot formulation in the treatment of prostatic cancer. Randomized dose-finding trial in Japan.

Ninety patients with advanced prostatic cancer (15 with stage B, 23 with stage C, and 52 with stage D) were randomized to receive 0.9, 1.8, or 3.6 mg, respectively, of Zoladex depot subcutaneous injection every 28 days for 12 weeks. The serum levels of LH, FSH, and testosterone were elevated after the first injection, and followed by a significant decrease. The suppression of testosterone levels in the blood to castrate levels was observed in all patients except two treated with 0.9 mg. Objective response (CR and PR) was seen in 63.6% (0.9 mg), 47.8% (1.8 mg), and 68% (3.6 mg) of patients according to the Japanese Prostatic Group Criteria. Subjective improvement (performance status, analgesic consumption) was also observed in 75-88% of patients but without a statistically significant difference between each dose group. Only minor adverse effects were found during the treatments. The drug was detected dose dependently in the blood by radioimmunoassay. These results suggest that endocrine therapy with Zoladex depot in doses of 3.6 mg subcutaneously every 4 weeks is a useful alternative to surgical castration in patients with prostatic cancer.

Aged↗

Clinical evaluation of urethral tumors based on a simple classification system.

A simplified classification for primary urethral tumors is proposed. The T stage for tumors of male or female and of the upper or lower urethra has been combined into a single system. The system has been applied to 104 cases of urethral tumors. Although the cases were not necessarily very well qualified, a retrospective survival study demonstrated a general trend to a poorer prognosis in higher stages. Such a unified system might be useful for a simple classification of urethral tumors, a rare neoplasm with various clinical manifestations depending on sex or tumor site.

Adenocarcinoma↗

A prospective, randomized controlled study on the treatment of stage C and stage D prostatic cancer with estracyt in combination with other chemotherapeutic agents.

The present study was designed to investigate the efficacy of various combinations of chemotherapeutic agents in the treatment of prostatic cancer in a group refractory to antiandrogenic therapy (Group 1) and in a previous untreated group (Group 2). Therapeutic combinations of Estracyt (E) + Peplomycin (P) + Doxorubicin (Do) and P + Do + 5 FU (F) in Group 1 and E + P, Honvan (Ds) + P and E in Group 2 were carried out. The main objectives of this study were estimations of the efficacy of E and P in relation to the refractory cases of Group 1 and the efficacy of the combination E + P, in Group 2. This is the first such prospective, randomized, controlled study to be carried out in Japan in relation to prostatic cancer. The results obtained in the present study indicated that chemotherapeutic regimens including E provide some enhanced efficacy, but that the efficacy with regard to refractory cases is poor (23.1-27.3%), as has been reported of studies conducted in the USA and Europe. With regard to previously untreated cases, the E + P regimen achieved a relatively higher response rate than the other treatments (72.7 vs 44.5 or 50.0%). In the comparison of survival times and survival curves, there were no statistically significant differences among the various treatment subgroups. A comparison of survival curves revealed the interesting finding that the PAP-related response showed a clear correlation to the survival curves of Group 2 patients.

Aged↗

[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↗

[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↗

[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↗

[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↗

[Five-year trend in new patients with prostatic carcinoma].

Seventy-four new cases of prostatic carcinoma treated between 1981 and 1985 were analyzed. The patients were between 40 and 86 years old with a mean age of 72.2 +/- 7.7 years. More than 70% of the patients had clinical stage C and D carcinoma. All cases proved histologically to be adenocarcinoma of the prostate. Eighteen patients had well differentiated, 21 moderately differentiated and 35 poorly differentiated adenocarcinoma. Various hormonal treatments were performed as the initial treatment in 88.9% (64/72) of the cases. Among them, 37 cases were treated by estrogen and 22 cases by luteinizing hormone releasing hormone analogues. Fourteen of 64 patients (21.9%) who received hormonal treatment discontinued the therapy within 10.1 +/- 9.1 months because of relapse of the disease or no therapeutic response. Salvage therapy following hormonal treatment were chemotherapy (9/14) and radiation therapy (4/14). During the 5-year follow up 12.1% (9/74) of the patients died due to prostatic carcinoma.

Adult↗

[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↗

[Current status of the treatment of urothelial tumors].

Cancer of the urinary bladder, renal pelvis and ureter is usually transitional cell carcinoma. One third of cases of urethral cancer are also transitional cell carcinoma. In planning the treatment for these urothelial cancers, the anatomic stage (Ta-T4), the histologic grade (1-3), tumor multiplicity and tumor size are generally taken into account. Superficial and low-grade tumors can usually be treated by transurethral resection. However, such patients run the risk of subsequent tumor recurrence in the bladder. This risk may be reduced by intravesical administration of anti-neoplastic agents and BCG. Diffuse carcinoma in situ (CIS) should be treated intravesically before deciding on surgical extirpation of the bladder. Patients with tumors showing deep muscle invasion are usually managed by surgery. The role of adjuvant chemotherapy and/or radiation therapy is currently under investigation. Patients with unresectable cancer and/or metastases are candidates for systemic chemotherapy. This form of therapy is now resulting in an increased number of complete and partial remissions. However, there is still no evidence that systemic chemotherapy prolongs the duration of survival, especially in patients showing partial remission.

Administration, Intravesical↗

[Trends in patterns of care for prostatic cancer in Japan: statistics of 9 institutions for 5 years].

Five hundred and sixty-five patients with prostatic cancer, who first visited 9 institutions in Japan between 1981 and 1985, were analyzed. The peak of age distribution was in the seventies. As clinical symptoms, disturbance on micturition was the most frequent and pain caused by metastasis was a complaint in approximately one tenth of the cases. Alkaline phosphatase measurement, prostatic biopsy, intravenous pyelography, bone scintigraphy, cystourethrography, and measurements of serum prostatic acid phosphatase and serum acid phosphatase were performed on more than 80% of the patients. The clinical stage was stage A1 in 6.2%, A2 in 3.7%, B in 14.9%, C in 20.7%, D1 in 7.4%, and D2 in 43.7%. According to the histological grade, well, moderately and poorly differentiated adenocarcinoma were observed in 20.4, 33.3 and 32.7%, respectively. Increased ratio of high grade to low grade was noticed in the lower age group as well as in the advanced stage. In this series, endocrine therapy was still accepted in most of the patients. Almost all were treated with hormonal medication and half of them had undergone bilateral orchiectomy. Surgery, radiation, chemotherapy or multidisciplinary therapy were attempted judging from the clinical stage and histological grade. However, old age restricted the therapeutic modality. Actuarial survival rate at 5 years for stage A1, A2, B, C, D1 and D2 was 89.2, 66.1, 72.7, 51.0, 47.5 and 28.0%, respectively. In the patients with stage D2, the 5-year actuarial rate of poorly differentiated adenocarcinoma was lower than that of well or moderately differentiated adenocarcinoma, even though more intensive therapy was given to the former.

Adenocarcinoma↗

Clinical evaluation of urothelial tumors of the renal pelvis and ureter based on a new classification system.

Clinical evaluation of 460 cases of urothelial tumors of the renal pelvis and ureter was performed using a new clinical classification system, since no systemic clinical classification such as the TNM system for bladder tumors has been available to date. ABC, and TS and TE categories were newly adopted. The former distinguishes tumor multicentricity, and the latter indicates the clinical tumor stage. Tumors arising in one organ and homolaterally are categorized as A, while those in both organs (ureter and renal pelvis) and/or in the bladder are B, and bilateral tumors are C. TS represents the tumors of pT1 and pT2, and TE represents pT3, and pT4. Tumors belonging to pB showed a poorer prognosis than pA tumors. The TS and TE staging system clearly reflected the histopathologic stage, and produced significant differences in relative survival rates. Regarding various prognostic factors, our series gave the same results as reported by other investigators. However, it should be stressed that female patients showed a poorer prognosis than male patients.

Adult↗

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.

A 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.

Adult↗