結腸直腸癌患者における好中球減少症予防のためのTAS-102の隔週投与

背景/目的：TAS-102は、転移性結腸直腸癌（MCRC）患者の全生存（OS）と無増悪生存（PFS）の大幅な改善をもたらしました。好中球減少症は最も一般的な有害事象であり、化学療法の継続に影響を与える重要な要因です。この遡及的研究では、TAS-102治療患者で頻繁に観察されるグレード≥3好中球減少症に関連する因子が検査されました。 患者と方法：2014年10月から2017年6月に福岡大学病院でTAS-102を投与されたCRCの41人の患者の医療記録が遡及的にレビューされました。階層化因子として、反応率、PFS、OS、および有害事象を分析しました。 結果：TAS-102とベバシズマブ併用療法では、PFSとOSの両方が有意に高かった。隔週の投与（7.1％）は、正常投与（44.4％）と比較して有意に少ない好中球減少症と関連していた。統計的に有意ではありませんが、隔週投与を伴うDCRは正常な投与の場合よりも優れていました。隔週と正常な投与レジメンの間でOS率に有意差は観察されませんでした。ただし、隔週のレジメンは、大幅に長期にわたるPFと関連していました。多変量解析により、OSのONODERAのインデックスとPFSの投与方法とNLRで有意差が認められました。 結論：薬物用量強度の変化のない隔週投与は、MCRC患者の好中球減少の減少と関連していた。TAS-102の効果と有害事象は、付随する薬物投与、投与方法、および栄養状態に関連していた。

BACKGROUND/AIM: TAS-102 has led to a significant improvement in overall survival (OS) and progression-free survival (PFS) of patients with metastatic colorectal cancer (mCRC). Neutropenia is the most common adverse event and an important factor impacting chemotherapy continuation. In this retrospective study, factors associated with grade ≥3 neutropenia, that is frequently observed in TAS-102-treated patients, were examined. PATIENTS AND METHODS: The medical records of 41 patients with CRC who received TAS-102 between October 2014 and June 2017 at the Fukuoka University Hospital were retrospectively reviewed. Response rate, PFS, OS, and adverse events were analyzed using KRAS mutation, administration method, concomitant drug administration, neutrophil-to-lymphocyte ratio (NLR), and Onodera's prognostic nutritional index (Onodera's index) as a stratification factors. RESULTS: Both PFS and OS were significantly higher with TAS-102 plus bevacizumab combination therapy. Biweekly administration (7.1%) was associated with significantly less neutropenia compared to normal administration (44.4%). DCR with biweekly administration was better than that with normal administration, although without statistical significance. No significant difference was observed in OS rates between the biweekly and normal administration regimens; however, the biweekly regimen was associated with significantly prolonged PFS. By multivariate analysis, a significant difference was noted in the Onodera's index for OS and in the administration method and NLR for PFS. CONCLUSION: Biweekly administration without a change in the drug dose intensity was associated with reduced neutropenia in patients with mCRC. The effects and adverse events of TAS-102 were associated with concomitant drug administration, administration method, and nutritional status.