Possible survival benefit of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin combination therapy (HD-MVAC) over conventional MVAC in metastatic urothelial carcinoma patients

Abstract

Eight patients with metastatic urothelial carcinoma received high-dose (HD)-MVAC therapy, which consisted of methotrexate (30 mg/m2) on day 1, vinblastine (3 mg/m2) on day 2, doxorubicin (30 mg/m2) on day 2 and cisplatin (70 mg/m2) on day 2 (14-day cycle). Patients were treated with granulocyte colony-stimulating factor (G-CSF) (100 microg) subcutaneously from day 4 to 10. For comparison, 7 patients with metastatic urothelial carcinoma who received conventional (C)-MVAC (28-day cycle) were enrolled in this study. Overall survival in the HD-MVAC group was significantly better than that in the C-MVAC group (p = 0.012, log rank test). The overall response rate for measurable metastatic lesions was similar in both groups (HD-MVAC, 62.5% vs. C-MVAC, 57.1%, p =0.622). The patients in the HD-MVAC group were able to receive significantly more courses than the C-MVAC group (HD-MVAC, median 3 courses vs. C-MVAC, 2 courses, p=0.045, Student's t test). The frequency of grade 3/4 toxicities was not statistically different between the 2 groups. HD-MVAC therapy rather than C-MVAC therapy may be advocated as a first-line chemotherapy for metastatic patients, since HD-MVAC is associated with a shorter period required for each course, a lower frequency of dose reduction and a possible benefit in terms of overall survival.

目的:転移性尿路上皮癌に対する初期治療としてのHigh-Dose-Intensity MVAC療法(HD-MVAC)の効果と有害事象を後ろ向きに評価し, 従来のMVAC療法(C-MVAC)と比較する。対象と方法:転移性尿路上皮癌患者8例に対し, 14日サイクルのHD-MVAC療法を行った。内容はmethotrexate(30mg/m2)day 1, vinblastine(3mg/m2)day 2, doxorubicin(30mg/m2)day 2, cisplatin(70mg/m2)day 2とした。顆粒球コロニー刺激因子(G-CSF)100μgをday 4～10まで連日皮下注射した。HD-MVACと比較するため, 従来の28日サイクルのC-MVACを受けた7例をこの研究に割り付けた。結果:HD-MVAC療法群患者の生存期間はC-MVAC療法群患者に比べ, 有意に長かった(p=0.012, log rank test)。評価可能病変に対する全奏効率は2群間で差がなかった(HD-MVAC, 62.5% vs C-MVAC, 57.1%, p=0.622)。HD-MVAC群患者はC-MVAC群患者に比較し, 有意に多くのコース数を受けることが出来た(HD-MVAC, 中央値3コース vs C-MVAC, 2コース, p=0.045, Student's test)。グレード3/4の有害事象の出現率は2群間で差がなかった。結論:HD-MVAC療法はC-MVAC療法よりも転移性尿路上皮癌に対する初期化学療法として推奨されるかもしれない。HD-MVACは各コースの治療期間を短縮できるほか, 抗癌剤投与量の減量の頻度を抑制し, 生存期間を延長する可能性がある。(著者抄録)