Inhibition of disease flare with diethylstilbestrol diphosphate and chlormadinone acetate administration for two weeks prior to slow-releasing leuprolide acetate in prostatic cancer patients

Abstract

未治療前立腺癌患者を無作為に3群に分けた.ホスフェストロール300mg/day(N=17), クロルマジノン100mg/day(N=16), 無治療(N=16)をLH-RHアゴニスト初回投与の2週間前より開始した.LH, テストステロン, PSA値を定期的に測定した.ホスフェストロール, クロルマジノンの前投与によりPSAは早期に低下した.テストステロンの平均値はホスフェストロール, クロルマジノンの前投与群で, アゴニスト投与後も治療前の値を越えることはなく, PSA平均値も前投与群ではアゴニスト投与後も有意の上昇を認めなかった.一方, 前投与を行わなかった群では初回のアゴニスト投与により一過性にテストステロン及びPSA平均値は治療前値よりも上昇した.以上の結果よりホスフェストロール300mg/day, クロルマジノン100mg/dayの2週間前投与は, 初回LH-RHアゴニスト投与後のフレアー現象に対し極めて有用である

To determine whether administration of estrogen or gestagen prior to luteinizing hormone-releasing hormone (LH-RH) agonist prevents disease flare in prostate cancer patients, we pretreated the patients with either diethylstilbestrol diphosphate (DES-P) 300 mg daily (N = 17) or chlormadinone acetate (CMA) 100 mg daily (N = 16) or none (N = 16) for two weeks before the initial injection of leuprolide acetate (L). Blood samples for prostatic specific antigen (PSA), testosterone (T), and luteinizing hormone were collected before CMA and DES-P administration, before and at 2, 7, 14, 28, 56, and 84 days after the first administration of leuprolide. The treatment with DES-P and CMA prior to LH-RH agonist induced an early decline of PSA. The mean PSA level showed no significant secondary rise in those patients with pretreatment after L administration. In the patients pretreated with DES-P or CMA, the mean serum T level never exceeded the pretreatment baseline after L administration. On the other hand, in the patients without DES-P or CMA, both serum T and PSA levels increased after the first administration of L. These results clearly demonstrate that pretreatment with DES-P 300 mg daily or CMA 100 mg daily for 2 weeks is quite effective to prevent disease flare after the first administration of L in patients with prostatic cancer.