Search

1)登録症例は16例で, 全例が適格例であった. 2)副作用は16例中8例に認められたが, 軽度で, 臨床上特に問題はなかった.乳房圧痛, 乳房腫脹等の副作用が50mg群で1例, 80mg群で3例及び100mg群で2例に認められた. 3)有効性に関しては, 各投与群の1例ないし2例において, PR以上の抗腫瘍効果が認められた.又, 排尿困難, 排尿痛, 夜間頻尿の改善がみられた. 4)血清中ホルモンでは, LH, FSH, testosterone及びestradiol濃度の上昇が認められた, 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.

ビカルタミド1日1回50mg群, 80mg及び100mgを12週間投与する3群比較の無作為化非盲検試験を実施した. 1)登録症例は124例で, 適格例は122例であった. 2)総合効果における奏効率は50mg群, 80mg群及び100mg群でそれぞれ50.5%, 61.0%及び53.7%であった. 3)PSAに対する奏効率は50mg群, 80mg群及び100mg群でそれぞれ84.2%, 92.7%及び97.6%であった. 4)副作用発現率は3群ほぼ6割で副作用による中止例は80mg群の1例のみで, 安全度において3群間に有意差はなかった.主な副作用は乳房腫脹, 乳房圧痛等であった, To investigate the efficacy and safety of bicalutamide (Casodex(R)) 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 ing 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.

1)内分泌療法未治療の前立腺癌症例に対し, 375mg/日の用量で単独療法として使用しえる。この際, testosterone産生阻害療法に比し, 「生活の質」が保たれる。2)内分泌療法再燃例に対しても, ある程度その効果が期待できる。3)フルタミドと他の精巣性testosterone阻害剤との併用で, その併用効果が期待できる。4)また, LH-RHアナログの投与によるflare-up現象をフルタミドを併用することにより予防することが可能である, The phase II study of flutamide, a pure anti-androgen, was performed to estimate the clinical doses on 165 hormone untreated or treated patients with prostatic cancer. The hormone-untreated patients were given orally flutamide of 90, 375, 750 or 1, 125 mg/day in three divided doses daily for 12 weeks. Responses were not observed at the 90 mg/day dose except for improvement of clinical symptoms. However, an objective response rate of 48.8-46.7% was obtained at 375-1, 125 mg/day doses. In hormone-treated patients including cases refractory to the previous hormonal treatment, the objective response rates were 13.3 and 8.3% in 375 and 750 mg/day flutamide groups, respectively. Side effects such as gynecomastia, nausea, vomiting, diarrhea, and abnormal laboratory findings such as the elevation of hepatic transaminases were observed. The incidence increased dose-dependently. Determinations of serum hormone levels revealed an increase in testosterone levels by the use of flutamide. In conclusion 375 mg/day of flutamide is the optimal dose in monotherapy for hormone-untreated patients with prostatic cancer, where the quality of life can be maintained compared with therapies involving testosterone suppression. This dose is also expected to show some efficacy in cases refractory to hormone treatment.

前立腺癌に対するRU 23908の有効性および安全性を検討するため, stage C, Dの前立腺癌患者47例に1日1回150または300 mg経口投与による早期第2相臨床試験を行った.対象病巣に対する効果では, 総合効果判定は40例中CR+PRが34例, 部位別効果は原発巣では40例中CR+PRが35例, 骨転移では22例中10例, リンパ節転移では6例中5例, 肺転移は1例のみにみられCRであり, PAP判定では34例中CR+PRは33例であった.臨床症状に対する改善率は骨疼痛8/9例, 排尿障害25/30例, P.S. 15/33例であった.副作用は調査症例数47例中29例にみられ, 中止例は7例あった.特殊な副作用として間質性肺炎が試験期間の12週以後の継続投与期間も含めて6例に認められ, その他2例では出現の可能性が否定できないと判定された, 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.

1)再燃前立腺癌82例に対する化学療法の効果をみるため新しく提唱した方法(泌尿器科紀要・投稿中)に基づき評価を行った.2)前立腺局所, 骨転移, 軟部組織転移, PAPの4項目を個別に評価し, それを合算して総合評価を行ったところ, PRとstableをそれぞれ19%および27%に認め, 両者は有意な生存期間の延長をみた.3)前立腺局所と骨転移は測定方法が鋭敏なものでないため, 総合評価との一致率が低かった.4)軟部組織とPAPは治療効果を鋭敏に反映した.特にPAPは異常値からの正常化が生存期間を延長する要因として認められた.5)化学療法により自覚症状が改善されることが多いが, 他覚的所見の総合評価とはかならずしも一致しないことが多かった.6)治療効果に影響を及ぼすものとして, 既治療の内容, performance state, 年齢, 病変数, stageがあったが, 初回治療時の組織学的分化度は関係がなかった.7)新しく提唱された評価方法の妥当性が認められた, Effect of chemotherapy for relapse of prostatic cancer was evaluated with new response criteria, in which four objective parameters including the prostate, bone metastasis, soft tissue metastasis and the serum acid phosphatase level estimated by radioimmunoassay or enzyme immunoassay were judged separately and then summarized to evaluate the response as complete response (CR), partial response (PR), stable and progressive disease (PD). Eighty-two patients were included in the study. Rate of PR and stable were 19% and 27%, respectively, and these two groups showed longer survival than those with PD. Evaluation of prostate and bone showed tendency to be discrepant with total judgement. Evaluation of soft tissues and prostatic acid phosphatase reflected the effect of chemotherapy. Chemotherapy often improved subjective symptoms but the effect did not parallel the total judgement in many cases. Factors influencing response of chemotherapy were mode of pretreatment, performance status, age, number of affected areas and clinical stage, but the grade at initial treatment was not correlated to response. The new criteria used in this study was valid for evaluation of response in prostatic cancer.

The efficacy of cytotoxic agents in the treatment of prostatic cancer is difficult to evaluate because objective, measurable lesions, such as lung, liver, skin, subcutaneous and nodal metastasis are often not found. However, most of the patients with advanced prostatic cancer have bone involvement and elevated serum acid-phosphatase in addition to the primary tumor. Exact clinical trials on such cases, especially phase II studies can not be performed without appropriate evaluations of these three parameters. The criteria of these three parameters offered by various study groups are reviewed and the relevant response criteria are proposed. A stable category was thought to be useful to evaluate the efficacy on the patients with progressing disease. In our proposal, overall assessment of response involves all objective parameters including these three parameters as well as both measurable and unmeasurable disease described in the WHO handbook for reporting results of cancer treatment.

9施設565例の初診時年齢は70歳代をピークとする分布を示した.来院時症状は排尿困難が72.2%と最も多く, 癌性疼痛を訴える例が13.6%あった.検査法では, アルカリ性ホスファターゼ, 前立腺生検, IVP, 骨シンチグラフィー, 尿道膀胱造影, 前立腺酸性ホスファターゼ, 酸性ホスファターゼなどが広く施行されていた.臨床病期では, A1 6.2%, A2 3.7%, B 14.9%, C 20.7%, D1 7.4%, D2 43.7%であり, 進行病期のものが多かった.組織学的分化度は, 高, 中, 低分化癌が, それぞれ20.4%, 33.3%, 32.7%であった.初診時年齢が低いほど, 分化度の低い癌がやや多くなる傾向がみられた.また進行病期のものほど, 低分化癌の占める割合が増加していた.治療として内分泌療法が多く行われ, 方法としてほぼ全例にホルモン剤が投与され, その約半数に除睾術が併用された.臨床病期や組織学的分化度を考慮し, 手術療法, 放射線療法, 化学療法や複数の治療を組み合わせた治療法もある程度は試みられていたが, 年齢による制約がみられた.臨床病期別実測5年生存率は, 病期A1 89.2%, A2 66.1%, B 72.7%, G 51.0%, D1 47.5%, D2 28.0%であった.D2において低分化癌の実測5年生存率は16.0%であり, 高中分化癌より悪かった, 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.