新たな経口薬は前立腺がん治療として有望なようである

ARMOR1スタディ：早期臨床データからgaleteroneは去勢抵抗性前立腺がんに対し安全で有効であることが示された
ARMOR1 study: Early clinical data show galeterone safe, effective against castration-resistant prostate cancer
去勢抵抗性前立腺がん（CRPC）患者における小分子経口薬galeterone（TOK-001）の副作用は限定的であり、多くの症例において前立腺特異抗原発現量が低下するとのphase Iのデータが2012年AACR学会で発表された。ARMOR1スタディにおいて研究者らはCRPC患者を、1日650mg、975mg、1300mg、1,950mgまたは2,600mgの漸増用量を1日単回でまたは複数回に分けて12週間内服する8つの用量群のいずれかに割り付けた。最大耐量に達した患者は一人もいなかった。ほとんどの副作用は軽症で、倦怠感、嘔気および下痢であった。15人の患者において一過性の重篤でない肝酵素上昇を認め、その多くが無症状であった。これらの患者のうち11人は一時的にgaleterone治療を中断し、6人は治療を再開したが肝酵素の再上昇は認めなかった。唯一発現した重篤な合併症は、スタチンを内服しており腎機能障害を有する患者における横紋筋融解であった。早期有効性試験において患者の49%で30%以上のPSA低下を認めた；これらの患者のうち11人では50%以上低下した。さらに、CTスキャンでは一部の患者において腫瘍サイズの減少が見られた。
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Patients with castration-resistant prostate cancer had limited side effects and in many cases a drop in prostate-specific antigen expression with galeterone (TOK-001), a small-molecule oral drug, according to phase I data presented at the AACR Annual Meeting 2012.

Galeterone works against castration-resistant prostate cancer (CRPC) by blocking the androgen receptor, reducing levels of the ligand that binds to the receptor and degrading the androgen receptor protein.

"This drug has a novel combined mechanism of action," said co-lead researcher R. Bruce Montgomery, M.D., associate professor of medical oncology at the University of Washington School of Medicine in Seattle, Wash. "Cancer cells are sly and mutate to get around drugs. The fact that this drug hits the prostate cancer cell in three different ways may help prevent resistance. It is a well-tolerated drug that could potentially be more effective than drugs we have now."

In the ARMOR1 study, Montgomery and colleagues assigned 49 patients with CRPC to one of eight dose regimens in single or split oral escalation doses of 650 mg, 975 mg, 1,300 mg, 1,950 mg or 2,600 mg every day for 12 weeks. None of the patients had received chemotherapy for their prostate cancer.

Researchers reported that no patients reached a maximum tolerated dose. Most side effects were minor and included fatigue, nausea and diarrhea. Researchers observed transient, non-serious elevated liver function tests in 15 patients, many of whom were asymptomatic. Eleven of these patients temporarily stopped galeterone treatment, and six returned to treatment with no recurring liver function test elevations. One serious complication occurred involving rhabdomyolysis in the setting of simvastatin therapy and underlying renal insufficiency.

In early efficacy tests, 49 percent of patients had prostate-specific antigen (PSA) reductions of 30 percent or more; 11 of these patients had reductions of 50 percent or more. In addition, CT scans revealed reduction in tumor size for some patients.

"Because the androgen receptor controls PSA expression, improved PSA response shows that the drug is getting to the target," said Montgomery. "For the majority of patients, to reduce their PSAs by 30 percent or more is quite good in a phase I dose-finding trial."

Researchers will investigate long-term safety and an assessment of efficacy in a phase II study that Tokai Pharmaceuticals has planned for the second half of 2012.