イメンド：アプレピタント（NK1受容体拮抗剤）の進行期肺癌患者への鎮咳効果

イメンド：アプレピタント
「抗悪性腫瘍剤（シスプラチン等）投与に伴う消化器症状（悪心、嘔吐）（遅発期を含む）」
https://www.kegg.jp/medicus-bin/japic_med?japic_code=00058171

ニューロキニン1（NK1）受容体拮抗作用（in vitro）

• NK1受容体に対する親和性

チャイニーズハムスター卵巣由来細胞株に発現させたヒトNK1受容体に対する125I-サブスタンスPの結合を阻害し、そのIC50値は0.1nmol/L、Kd値は86pmol/L（Hill係数＝1.1）であった。23)

• 各種NK受容体作動薬誘発反応に対する作用

サブスタンスP-O-メチルエステル（NK1受容体作動薬）誘発回腸縦走筋収縮に対し拮抗作用を示し、そのKa値は0.09±0.02nmol/L（n＝3）であった。一方、（Nle10）-ニューロキニンA〔4-10〕（NK2受容体作動薬）誘発による気管収縮、及びセンクタイド（NK3受容体作動薬）誘発による上頸神経節脱分極反応に対し、1μmol/Lの濃度において作用を示さなかった。23)

中枢作用性NK-1阻害剤としてアプレピタントを使用し、咳嗽軽減効果を検討


Aprepitant for Cough Suppression in Advanced Lung Cancer: A Randomized Trial

Vanita Noronha (American Board Certified in Hematology and Medical Oncology) et al.

DOI: https://doi.org/10.1016/j.chest.2019.11.048
CHEST
Available online 18 January 2020
https://www.sciencedirect.com/science/article/abs/pii/S0012369220300325


VAS、Manchester Cough in Lung Cancer Scale (MCLCS)の効果がプライマリエンドポイント
QOLスコア：EORTC QLQ-C30 と QLQ-LC13 and toxicity及び毒性はセカンダリ

平均VAS(mm表示)：ベースラインとday 9
アプレピタント 68→39、対照群 62 → 49 ; P＜0.001<0 .001="" p="">
<0 .001="" 23="" 25="" 30="" 33="" a="" adverse="" and="" aprepitant="" arm="" arms="" at="" baseline="" between="" control="" cough-specific="" day="" did="" different="" domain="" events.="" however="" improvement="" in="" increase="" led="" mclcs="" mean="" nine="" not="" overall="" p="" qol="" scores="" severe="" significant="" significantly="" the="" to="" two="" was="" were="">
平均MCLCSスコア：ベースラインとday 9
<0 .001="" p=""><0 .001="" 23="" 25="" 30="" 33="" a="" adverse="" and="" aprepitant="" arm="" arms="" at="" baseline="" between="" control="" cough-specific="" day="" did="" different="" domain="" events.="" however="" improvement="" in="" increase="" led="" mclcs="" mean="" nine="" not="" overall="" p="" qol="" scores="" severe="" significant="" significantly="" the="" to="" two="" was="" were="">アプレピタント33→23、対照群 30→ 25; P＜0.001
<0 .001="" p=""><0 .001="" 23="" 25="" 30="" 33="" a="" adverse="" and="" aprepitant="" arm="" arms="" at="" baseline="" between="" control="" cough-specific="" day="" did="" different="" domain="" events.="" however="" improvement="" in="" increase="" led="" mclcs="" mean="" nine="" not="" overall="" p="" qol="" scores="" severe="" significant="" significantly="" the="" to="" two="" was="" were="">
<0 .001="" p=""><0 .001="" 23="" 25="" 30="" 33="" a="" adverse="" and="" aprepitant="" arm="" arms="" at="" baseline="" between="" control="" cough-specific="" day="" did="" different="" domain="" events.="" however="" improvement="" in="" increase="" led="" mclcs="" mean="" nine="" not="" overall="" p="" qol="" scores="" severe="" significant="" significantly="" the="" to="" two="" was="" were="">QOLの有意差認めないが、咳嗽関連QoLドメイン改善
<0 .001="" p=""><0 .001="" 23="" 25="" 30="" 33="" a="" adverse="" and="" aprepitant="" arm="" arms="" at="" baseline="" between="" control="" cough-specific="" day="" did="" different="" domain="" events.="" however="" improvement="" in="" increase="" led="" mclcs="" mean="" nine="" not="" overall="" p="" qol="" scores="" severe="" significant="" significantly="" the="" to="" two="" was="" were="">
<0 .001="" p=""><0 .001="" 23="" 25="" 30="" 33="" a="" adverse="" and="" aprepitant="" arm="" arms="" at="" baseline="" between="" control="" cough-specific="" day="" did="" different="" domain="" events.="" however="" improvement="" in="" increase="" led="" mclcs="" mean="" nine="" not="" overall="" p="" qol="" scores="" severe="" significant="" significantly="" the="" to="" two="" was="" were="">重度副事象差認めず
<0 .001="" p=""><0 .001="" 23="" 25="" 30="" 33="" a="" adverse="" and="" aprepitant="" arm="" arms="" at="" baseline="" between="" control="" cough-specific="" day="" did="" different="" domain="" events.="" however="" improvement="" in="" increase="" led="" mclcs="" mean="" nine="" not="" overall="" p="" qol="" scores="" severe="" significant="" significantly="" the="" to="" two="" was="" were="">
<0 .001="" p=""><0 .001="" 23="" 25="" 30="" 33="" a="" adverse="" and="" aprepitant="" arm="" arms="" at="" baseline="" between="" control="" cough-specific="" day="" did="" different="" domain="" events.="" however="" improvement="" in="" increase="" led="" mclcs="" mean="" nine="" not="" overall="" p="" qol="" scores="" severe="" significant="" significantly="" the="" to="" two="" was="" were="">

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<0 .001="" p=""><0 .001="" 23="" 25="" 30="" 33="" a="" adverse="" and="" aprepitant="" arm="" arms="" at="" baseline="" between="" control="" cough-specific="" day="" did="" different="" domain="" events.="" however="" improvement="" in="" increase="" led="" mclcs="" mean="" nine="" not="" overall="" p="" qol="" scores="" severe="" significant="" significantly="" the="" to="" two="" was="" were="">
<0 .001="" p=""><0 .001="" 23="" 25="" 30="" 33="" a="" adverse="" and="" aprepitant="" arm="" arms="" at="" baseline="" between="" control="" cough-specific="" day="" did="" different="" domain="" events.="" however="" improvement="" in="" increase="" led="" mclcs="" mean="" nine="" not="" overall="" p="" qol="" scores="" severe="" significant="" significantly="" the="" to="" two="" was="" were="">
<0 .001="" p=""><0 .001="" 23="" 25="" 30="" 33="" a="" adverse="" and="" aprepitant="" arm="" arms="" at="" baseline="" between="" control="" cough-specific="" day="" did="" different="" domain="" events.="" however="" improvement="" in="" increase="" led="" mclcs="" mean="" nine="" not="" overall="" p="" qol="" scores="" severe="" significant="" significantly="" the="" to="" two="" was="" were="">
<0 .001="" p=""><0 .001="" 23="" 25="" 30="" 33="" a="" adverse="" and="" aprepitant="" arm="" arms="" at="" baseline="" between="" control="" cough-specific="" day="" did="" different="" domain="" events.="" however="" improvement="" in="" increase="" led="" mclcs="" mean="" nine="" not="" overall="" p="" qol="" scores="" severe="" significant="" significantly="" the="" to="" two="" was="" were="">統計学的には効果あるようだが、臨床的に実感するほどの効果になるのだろうか？