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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)1980～1990年に京大病院に入院した前立腺癌症例の223例中, 109症例に合成エストロゲンが投与され, そのうち53例になんらかの副作用を認めた。2)合成エストロゲンの副作用は心臓疾患:20.2%, 体液貯留(体重増加および浮腫):14.7%, 高血圧:13.8%などで, 5症例は致死的であった。3)合成エストロゲンの副作用が認められた53症例のうち, 46例の症例においては投与を中止し, 他の治療法に変更した。4)心・血管疾患の既往歴, 心電図異常は副作用発現の危険因子である, Since the introduction of hormonal treatment for prostatic cancer by Huggins and Hodges in 1941, severe side effects of synthetic estrogen, which have overcome its benefit, have been reported in the U.S.A. and in European countries. However, in Japan the adverse effects of estrogen have been reported to be milder than in western countries, and estrogen still has an important role in the treatment of prostatic cancer in Japan. In this communication, the side-effects of synthetic estrogen administered to 109 prostatic cancer patients, who were admitted to Kyoto University Hospital between 1980-1990 are reported. Fifty-three (48.6%) of the 109 patients suffered adverse side effects of the estrogen, specifically cardiac disease (20.2%), fluid retention (14.7%) and hypertension (13.8%). Five of these patients died. Among the risk factors analyzed, daily dose, past history of cardio-vascular disease and ECG abnormalities were significantly correlated with the appearance of adverse effects. The reasons why the frequency of lethal side-effects is lower in our cases compared to findings reported by the Veterans Administration group may be the lower daily dose and cessation of estrogen administration when mild adverse effects appear and some other unknown factors, although the background of the patients and method of analysis are not comparable among them. The overall frequency of side-effects in prostatic cancer patients administered estrogen in our cases is not necessarily lower than in western countries, but the severity of the side effects was milder in our cases. We must be a ware of the potential adverse effects of estrogen.

The quality of life (QOL) was studied on 31 prostatic cancer (PC) patients, being followed at our out-patient-clinic during a relapse-free period. Fifteen of them were under treatment with a slow releasing LH-RH analogue (TAP-144 SR Depot) (TAP) and the other 16 prostatic cancer patients with synthetic estrogen (Honvan) (DES). The QOL of 37 benign prostatic hyperplasia (BPH) patients on conservative treatment was also studied. Concerning their general feeling of health, the prostatic cancer patients on TAP treatment felt subjectively better than those on DES. The social life of the patients on TAP or those who had BPH was less affected than that of those on DES. The quality of sexual life was worse for the prostatic cancer patients on both TAP and DES treatment than for the BPH patients.

前立腺癌23例に対し, MRIを施行した.内6例に全摘術を施行したが, stagingはMRIがperiprostatic plexusの描出や精嚢浸潤の判断の容易さなどにより最も正確であった.また限局した癌は, MRIではT2-WI上high intensityを示すべき外腺内のlow intensity areaとして描出され, USでは, hypoechoic areaとして描出された.広範な癌ではMRIでは内外腺の境界線の一部または全部の消失として判断できたが, USでは全体にheterogenousなエコーを示した.CTは限局性の癌に対してほとんど不用であった, Twenty-three pathologically revealed prostatic cancer patients were examined by magnetic resonance imaging (MRI), computed tomography (CT) and transrectal ultrasonography, (US) and 6 of them underwent radical prostatectomy. A localized prostatic cancer was identified as a low intensity area in the outer zone with high intensity or showed a partial or total destruction of the border line between the internal and the outer zone when cancer invaded into the internal zone from the outer zone, on T2 weighted image of MRI, as we have already reported. On US, a localized prostatic cancer was identified as a hypoehoic area in the outer zone, and showed a heterogeneous image when cancer enlarged. On CT, a localized cancer could not be identified. A diagnostic criteria for local staging by MRI was made and preoperative staging were done in 6 total prostatectomy cases. The accuracy of preoperative staging of cancer seemed to be the highest by MRI, because it was more accurate in diagnosing the extracapsular invasion, seminal vesicle invasion and bladder neck invasion of the tumor than by CT and US.

限局性前立腺癌70例にstaging pelvic lymphadenectomy(うち前立腺全摘術37例)を行い, リンパ節の転移様式およびstage D1前立腺癌の予後について検討を加えた.1) 70例中21例にリンパ節転移を認めた.2) stage別のリンパ節転移頻度は, stage A2で4/11, stage B1で1/19, stage B2で4/20, stage Cで12/20であった.3) grade別のリンパ節転移頻度は, 高分化腺癌で1/21, 中分化腺癌で11/36, 低分化腺癌で9/13であった.低分化になるほど転移リンパ節のnodal volumeは増加していた.4) stage D1症例のdiscase free survivalは, リンパ節転移陰性例に比較して有意(p, Between 1982 and 1988, 70 patients with proved prostatic adenocarcinoma in stages A2 to C underwent pelvic lymphadenectomy. Median followup has been 30 months. Radial prostatectomy was done in 37 patients, 3 of whom were followed by immediate hormone therapy. Twenty eight patients received radiotherapy alone except one combined with hormone therapy. The remaining 5 patients were treated hormonaly alone. Pelvic lymph node metastases were noted in 21 of the 70 patients (30%). High stage and poor histological differentiation were associated with a significantly higher probability of pelvic lymph node metastases. Poor histological differentiation was more likely to be found in patients with multiple or gross node involvement. Progression of the disease, almost exclusively bony metastases, occurred in 10 of the 21 patients who had positive pelvic nodes and in 7 of the 49 patients with negative nodes (p less than 0.01). According to Kaplan-Meier projections, 1, 3 and 5 year percent disease free survival were, respectively; 73%, 32% and 32% for patients with positive node, and 93%, 82% and 75% for patients with negative nodes. Disease-free survival of stage D1 patients was significantly worse than that of patients with negative nodes (p less than 0.001, Generalized-Wilcoxon test). We divided 21 patients with pelvic nodal metastases into subgroups based upon the volume and extent of nodal disease; 7 patients with a single microscopic nodal involvement and 14 patients with multiple or gross nodal involvement. There was no significant difference in disease free survival between the two groups. 9 of the 21 patients were given hormonal treatment immediately and on the contrary, 12 were followed without hormonal treatment. However, projected disease free survival differed little between the groups. These data suggest that patients with positive nodes appear to have equivalent adverse biologic potential and should be considered candidates for early systemic treatment.

PAP, γ-Sm, PAの同時測定を行い, それぞれの有用性と相関性を検討したので報告する.臨床病期の進行や原発病巣の範囲と測定値とは相関しなかった.PA-1よりPA-2が高値を示すことが多く, 検出率はPA-2, 特異性はPAP, 診断精度はPA-1が最も良好であった.未治療前立腺癌における陽性率は三者併用の陽性率が高かった.全測定検体では各マーカー値間の相関係数は高くなく, 三者は臨床的に異なるマーカーと考えられた.組織学的分化度と各マーカー測定値との間に一定の関係は見られなかった.低分化型の症例では治療後もPAが異常値に止まる傾向があった.いずれのマーカーでも再燃例は制癌例に比べて有意に高い値であった.また再燃例ではPA-1が最も高い異常値率を示した, We measured the prostatic acid phosphatase (PAP), gamma-Seminoprotein (gamma-Sm) and prostate specific antigen (PA) in the serum of 862 patients with various urologic diseases including 89 patients with prostatic cancer. We used a PAP radioimmunoassay kit, gamma-Sm enzyme immunoassay kit, Markit-F-PA enzyme immunoassay kit and PA test Wako enzyme immunoassay kit. Serum PA level in advanced prostatic carcinoma (stage C, D) tended to be higher than that in early stage cancer (stage A, B). The Wako kit gave a higher PA than the Markit-F in each stage. The sensitivity rate of Wako PA test was the highest (81%) of all kits. The specificity rate of PAP was the highest (83%), and the accuracy rate of Markit-F PA was the highest (79%). The positive rate in the combined assay of PAP, gamma-Sm and PA in prostatic cancer was higher than that in the single assay of each tumor marker. We regarded PAP, gamma-Sm and PA as clinically different tumor markers, because their serum level did not correlate definitely. No apparent correlation was found between histopathological grade and the level of each tumor marker. The level of PAP, gamma-Sm and PA in the reactivated patients was significantly higher than that of the well-controlled patients. In the reactivated patients, the positive rate of Markit-F PA was the highest (89%) of all the kits.