徐放性LH-RH agonist製剤,TAP-144-SRの前立腺癌に対する臨床第3相試験

Abstract

TAP-144-SRの前立腺癌に対する比較対照試験をリン酸ジエチルスチルベストロールを対照薬として行った.有効性では, 前立腺癌の判定基準の適格例で, TAP群54.5%(36/66), 対照群47.1%(32/68)のPR例が得られ, 両群間に有意差はみられなかった.病巣別効果や自他覚症状に対する効果でも両群間に差はみられなかった.PAPなど腫瘍マーカーに対して対照群の方が有意に優れる効果を示した.内分泌効果では両群とも全例で血清testosteroneがcastration levelに低下した.安全性については, 副作用発現率はTAP群64.1%(41/64)に対し, 対照群は95.4%(62/65)と有意に高く, 対照群で4例が副作用のため試験が中止された.主治医判定による全般安全度では"問題あり"と判定された症例はTAP群6.3%(4/64), 対照群36.9%(24/65)であった.主治医判定による有用度では"有用"以上でみると, TAP群65.6%(42/64), 対照群52.3%(34/65)であった

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.