ホルモン不応性前立腺癌の治療は最近大きく発展しています。
ここからはドセタキセル以外の新規治療薬についてのまとめです。
COUGAR 301 trialでドセタキセル後のアビラテロンの有効性が示され
AFFIRM trialでドセタキセル後のエンザルタミドの有効性が示されました。
米国ではすでにFDAの承認を受けて使用されていますが、残念ながら2剤とも日本では承認されていませんので、使用するとなると個人輸入か、タイミングよく治験にエントリーできた人に限られています。
（日本では2013年5月にアステラスがエンザルタミドの承認申請を行っています）
さらに、COUGAR 302 trialでドセタキセル使用前のアビラテロンの有効性が示され、FDAで使用を承認されています。
ドセ前のエンザルタミドの有効性と安全性評価のためにREVAIL trialが現在行われており、近い将来結果が報告されるでしょう。
Both of these drugs were tested in clinical trials of CRPC patients who had already received docetaxel (the COUGAR 301 trial of abiraterone and the AFFIRM trial of enzalutamide). Those data led to the approval of the agents for use in CRPC patients who had received docetaxel. The US Food and Drug Administration (FDA) approved abiraterone for this indication in April 2011 and approved enzalutamide in August 2012.
Both drugs were then investigated in CRPC patients who had not previously been treated with docetaxel (the COUGAR 302 trial of abiraterone and the PREVAIL trial of enzalutamide). Data from COUGAR 302 led to FDA approval in December 2012 of abiraterone for CRCP patients not previously treated with docetaxel. The enzalutamide trial is still ongoing.
ところで、
これらの使用順序はどうすればいいのでしょうか？
sequential治療についてどの順番で使用していくのが最適なのか？
まだまだこれからの検討になりますが、２つ小さな研究結果が報告されています。
フランスからの報告
Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100)
Oxford JournalsMedicine Annals of Oncology Volume 24, Issue 7Pp. 1807-1812.
Background Androgen receptor (AR) signalling remains critically important in metastatic castration-resistant prostate cancer (mCRPC) as confirmed by recent phase III trials, showing a survival advantage for abiraterone acetate and enzalutamide (MDV3100). The antitumour activity of abiraterone and prednisolone in patients pre-treated with enzalutamide is as yet unknown.
Patients and methods We investigated the antitumour activity of abiraterone and prednisolone in patients with mCRPC who had progressed following treatment with docetaxel (Taxotere) and enzalutamide. Clinical data were retrospectively analysed for prostate-specific antigen (PSA) and RECIST responses, clinical benefit and survival.
Results Thirty-eight patients were included in the analysis. The median age was 71 years (range 52–84); metastatic sites included bone disease in 37 patients (97%), lymph nodes in 15 patients (39%) and visceral disease in 10 patients (26%). Abiraterone was well tolerated. Three patients (8%) attained a PSA response, defined as ≥50% decline in PSA confirmed after ≥4 weeks, while seven patients (18%) had a ≥30% PSA decline. The median progression-free survival (PFS) was 2.7 months (95% CI 2.3–4.1). Of the 12 patients assessable radiologically, only 1 (8%) attained a confirmed partial response.
Conclusion Abiraterone and prednisolone have modest antitumour activities in patients with mCRPC pretreated with docetaxel and enzalutamide.
カナダからの報告
Clinical activity of abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after enzalutamide
Oxford JournalsMedicine Annals of Oncology Volume 24, Issue 7Pp. 1802-1807
Background Abiraterone acetate and enzalutamide both improve outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). Optimal sequencing for these agents and whether cross-resistance occurs is unknown.
Methods Multicentre review of patients with mCRPC treated with abiraterone acetate and prednisone after progressing on enzalutamide. Primary objective was to determine abiraterone acetate response.
Results Thirty patients identified from four North American centres. At abiraterone initiation, median age was 70 years (56–84 years); 70% had ECOG performance status of 0–1; all had prior docetaxel. Median prior enzalutamide treatment duration was 41 weeks (6–95 weeks), with 70% (21 of 30) having a ≥30% prostate-specific antigen (PSA) decline. Median abiraterone acetate treatment duration was 13 weeks (1–52). No objective radiographic responses were observed. Median abiraterone time to progression (PSA, objective or symptomatic) was 15.4 weeks [95% confidence interval (CI) 10.7–20.2]. Median overall survival was 50.1 weeks (95% CI 28.3–72.0). Three patients had a ≥30% PSA decline with abiraterone. Two of these patients had PSA progression as best response with prior enzalutamide.
Conclusions In this study of patients progressing after enzalutamide, treatment with abiraterone was associated with a modest response rate and brief duration of effect. Primary progression on enzalutamide may not preclude a response to abiraterone.
どちらの報告も、エンザルタミド後のアビラテロンは効果が落ちるかもしれないとしている。
では逆はどうなのか？
実際米国ではアビラテロン→ドセ→エンザルタミドの順番に治療されている人が多いとのこと。
今後の報告が待たれる。