アムルビシンの臨床評価

摘要

目的．新規抗癌剤のアムルビシン（AMR）の小細胞肺癌（SCLC）ならびに非小細胞肺癌（NSCLC）に対する有効性を検証する．方法，進行NSCLCに対する第Ⅰ/Ⅱ相試験，進展型SCLCに対する第Ⅱ相試験とシスプラチンとの併用第Ⅰ/Ⅱ相試験の結果を検討した．結果．前臨床試験の結果から3日間連日投与が採択，未治療進行NSCLCに対し第Ⅰ/Ⅱ相試験が行われた．用量規定因子は白血球，血小板減少，消化管障害，最大耐用量50mg/m~2，第Ⅱ相試験への推奨量が45mg/m~2となった．NSCLCの第Ⅱ相試験は2つ行われ，奏効率はそれぞれ27.9％，18.3％であった．進展型SCLCの第Ⅱ相試験では，奏効率75.8％（完全寛解率9.1％），生存期間中央値11.7月，シスプラチンとの併用第Ⅰ/Ⅱ相試験では推奨量AMR40mg/m~2，シスプラチン60mg/m~2，奏効率88.6％（完全寛解率9.1％），1年生存率65.3％であった．結論．NSCLCならびにSCLCに対し，有望な結果が報告されている．今後，さらなる臨床試験によってAMRの臨床実地における位置づけがはっきりするものと思われる．Objective. To assess the efficacy of a new agent, Amrubicin (AMR), for non-small-cell lung cancer(NSCLC) and small-cell lung cancer (SCLC). Methods. We reviewed the results of phase Ⅰ/Ⅱstudies using AMR for advanced NSCLC, phase Ⅱstudies using AMR for extensive disease (ED) -SCLC and phase Ⅰ/Ⅱstudies using AMR in combination with cisplatin for ED-SCLC. Results. Phase Ⅰ/Ⅱstudies for previously untreated advanced NSCLC were carried out using the dosing regimen of intravenous (iv) administration on 3 consecutive days as recommended by the pre-clinical studies. The dose-limiting toxicities were leukopenia, thrombocytopenia and gastrointestinal disturbance, the maximum tolerated dose was 50mg/m~2/day and the recommended dose for phase Ⅱstudies was 45mg/m~2/day. Two phase Ⅱstudies for advanced NSCLC were conducted and showed response rates of 27.9% and 18.3%, respectively. The phase Ⅱstudies for ED-SCLC revealed a response rate of 75.8% (complete response rate 9.1%), and a median survival time of 11.7 months. The phase Ⅰ/Ⅱstudy in combination with cisplatin showed the recommended dose was AMR 45mg/m~2/day and cisplatin 60mg/m~2, the response rate was 88.6% (complete response rate 9.1%), and the one-year survival rate was 65.3%. Conclusion. These results are promising for the efficacy of AMR against NSCLC and SCLC. Further clinical trials will make clear whether AMR offers a significant benefit for practical medical treatment of lung cancer.