Nilotinib versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia
新規診断された慢性骨髄性白血病(CML)におけるニロチニブとイマチニブの比較
Background Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome–positive chronic myeloid leukemia (CML) in the chronic phase.
背景： ニロチニブはイマチニブより効果の高いBCR-ABL阻害剤であると示された．我々は，新規診断されたフィラデルフィア染色体陽性慢性骨髄性白血病(CML)の慢性期患者において，ニロチニブの効能と安全性をイマチニブと比較して評価した．
Methods In this phase 3, randomized, open-label, multicenter study, we assigned 846 patients with chronic-phase Philadelphia chromosome–positive CML in a 1:1:1 ratio to receive nilotinib (at a dose of either 300 mg or 400 mg twice daily) or imatinib (at a dose of 400 mg once daily). The primary end point was the rate of major molecular response at 12 months.
方法：無作為化非盲検他施設第3相臨床試験研究において，慢性期フィラデルフィア染色体陽性CML患者846例を1:1:1の比率でニロチニブ(用量は300mg/日か400mg/日で，1日2回服用)・イマチニブ(用量は400mg/日で，1日1回服用)に割り当てた．主要評価項目は12ヶ月時点における主要分子学的反応率とした．
Results At 12 months, the rates of major molecular response for nilotinib (44% for the 300-mg dose and 43% for the 400-mg dose) were nearly twice that for imatinib (22%) (P<0.001 for both comparisons). The rates of complete cytogenetic response by 12 months were significantly higher for nilotinib (80% for the 300-mg dose and 78% for the 400-mg dose) than for imatinib (65%) (P<0.001 for both comparisons). Patients receiving either the 300-mg dose or the 400-mg dose of nilotinib twice daily had a significant improvement in the time to progression to the accelerated phase or blast crisis, as compared with those receiving imatinib (P=0.01 and P=0.004, respectively). No patient with progression to the accelerated phase or blast crisis had a major molecular response. Gastrointestinal and fluid-retention events were more frequent among patients receiving imatinib, whereas dermatologic events and headache were more frequent in those receiving nilotinib. Discontinuations due to aminotransferase and bilirubin elevations were low in all three study groups.
結果：12ヶ月時点で，ニロチニブの主要分子学的反応率(300mg用量で44%，400mg用量で43%)は，イマチニブのほぼ2倍(22%)であった(両比較P値<0.001)．12ヶ月経過までの細胞遺伝学的完全寛解率は，イマチニブ(65%)に比べてニロチニブ(300mg用量で80%，400mg用量で78%)で有意に高かった．300mgおよび400mgのニロチニブを1日2回投与された患者は，イマチニブを投与された患者に比べて，病期進行および芽球急性転化までの時間が有意に改善した(それぞれP値=0.01，P値=0.004)．病期進行および芽球急性転化に至った患者で主要分子学的反応が認められた人はいなかった．胃消化管副作用と水分貯留副作用はイマチニブ投与群で多かったが，皮膚副作用と頭痛はニロチニブ投与群で多かった．アミノトランスフェラーゼとビリルビン濃度の上昇に伴う不快感は3群全てで低かった．
Conclusions Nilotinib at a dose of either 300 mg or 400 mg twice daily was superior to imatinib in patients with newly diagnosed chronic-phase Philadelphia chromosome–positive CML. (ClinicalTrials.gov number, NCT00471497 [ClinicalTrials.gov] .)
結論：新規診断された慢性期フィラデルフィア染色体陽性CML患者において，ニロチニブ300mgおよび400mg1日2回服用は，イマチニブよりも優れていた．(臨床試験機構ナンバーNCT00471497)
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