PARP　partB  + olaparib   ΔE＝ー7.3　RSMD:2.018～3.074

表面上に結合しているようであるがαヘリックスの間に入ってアロステリック効果を出すであろう

Patients and methods: OlympiAD, a Phase III, randomized, controlled, open-label study (NCT02000622), enrolled patients with a germline BRCAm and HER2-negative mBC who had received ≤2 lines of chemotherapy for mBC. Patients were randomized to olaparib tablets (300 mg bid) or predeclared TPC (capecitabine, vinorelbine, or eribulin). OS and safety were secondary end points.

Results: A total of 205 patients were randomized to olaparib and 97 to TPC. At 64% data maturity, median OS was 19.3 months with olaparib versus 17.1 months with TPC (HR 0.90, 95% CI 0.66-1.23; P = 0.513); median follow-up was 25.3 and 26.3 months, respectively. HR for OS with olaparib versus TPC in prespecified subgroups were: prior chemotherapy for mBC [no (first-line setting): 0.51, 95% CI 0.29-0.90; yes (second/third-line): 1.13, 0.79-1.64]; receptor status (triple negative: 0.93, 0.62-1.43; hormone receptor positive: 0.86, 0.55-1.36); prior platinum (yes: 0.83, 0.49-1.45; no: 0.91, 0.64-1.33). Adverse events during olaparib treatment were generally low grade and manageable by supportive treatment or dose modification. There was a low rate of treatment discontinuation (4.9%), and the risk of developing anemia did not increase with extended olaparib exposure.

1. 警告

2. 禁忌

4. 効能または効果

○白金系抗悪性腫瘍剤感受性の再発卵巣癌における維持療法

○BRCA遺伝子変異陽性の卵巣癌における初回化学療法後の維持療法

○相同組換え修復欠損を有する卵巣癌におけるベバシズマブ（遺伝子組換え）を含む初回化学療法後の維持療法

○がん化学療法歴のあるBRCA遺伝子変異陽性かつHER2陰性の手術不能又は再発乳癌

○BRCA遺伝子変異陽性かつHER2陰性で再発高リスクの乳癌における術後薬物療法

○BRCA遺伝子変異陽性の遠隔転移を有する去勢抵抗性前立腺癌

○BRCA遺伝子変異陽性の治癒切除不能な膵癌における白金系抗悪性腫瘍剤を含む化学療法後の維持療法

AUTODOCKではOLAPARIBはｐ５３阻害作用が多少ある

上の図のようにNAD産生のためにPARPは必要でこのことは貧血にもつながる。PARP阻害をするなら、トリプトファンを多く含む食品を摂取することが望ましい