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软组织肉瘤诱导期帕唑帕尼治疗的相对剂量强度:其与帕唑帕尼应答者预后的关系

Relative Dose Intensity of Induction-Phase Pazopanib Treatment of Soft Tissue Sarcoma: Its Relationship with Prognoses of Pazopanib Responders.

作者信息

Nakano Kenji, Funauchi Yuki, Hayakawa Keiko, Tanizawa Taisuke, Ae Keisuke, Matsumoto Seiichi, Takahashi Shunji

机构信息

Department of Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.

Department of Orthopedic Surgical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.

出版信息

J Clin Med. 2019 Jan 8;8(1):60. doi: 10.3390/jcm8010060.

Abstract

The approved standard dose of pazopanib is 800 mg per day, but the appropriate dose of pazopanib to treat soft tissue sarcoma (STS) patients in real-world practice is controversial. Of 124 STS patients treated with pazopanib, we retrospectively analyzed the cases of STS patients who achieved progression-free survival at 12 weeks by pazopanib treatment as pazopanib responders, and we evaluated their relative dose intensity (RDI) in the initial 12 weeks (12W-RDI). We enrolled 78 STS patients in the analyses as pazopanib responders, and 54 patients of the 78 pazopanib responders (69%) were able to maintain 12W-RDI ≥80%. In landmark analyses, patients with 12W-RDI of 80% ≥80% had significantly longer progression-free survival compared to those with 12W-RDI <80% (30.7 weeks vs. 22.0 weeks, hazard ratio [HR]: 0.56 [95%CI: 0.33⁻0.94], = 0.026). The most frequently observed reasons of treatment interruption and/or dose reduction of pazopanib during the initial 12 weeks were anorexia and liver function disorders. Liver toxicity was the adverse event most frequently observed in the 12W-RDI <80% patients throughout the treatment periods. Based on our results, it appears that maintaining as high a dose intensity as possible that is tolerable-at least during the initial 12 weeks-is likely to be the better option in pazopanib treatment for STS patients.

摘要

帕唑帕尼的批准标准剂量为每日800毫克,但在实际临床中,用于治疗软组织肉瘤(STS)患者的帕唑帕尼合适剂量存在争议。在124例接受帕唑帕尼治疗的STS患者中,我们回顾性分析了经帕唑帕尼治疗12周后达到无进展生存期的STS患者病例,将其作为帕唑帕尼反应者,并评估了他们在最初12周的相对剂量强度(12W-RDI)。我们纳入了78例STS患者作为帕唑帕尼反应者进行分析,78例帕唑帕尼反应者中有54例患者(69%)能够维持12W-RDI≥80%。在标志性分析中,12W-RDI≥80%的患者与12W-RDI<80%的患者相比,无进展生存期显著更长(30.7周对22.0周,风险比[HR]:0.56[95%CI:0.33⁻0.94],P = 0.026)。在最初12周内,帕唑帕尼治疗中断和/或剂量减少最常见的原因是厌食和肝功能障碍。在整个治疗期间,肝毒性是12W-RDI<80%患者中最常观察到的不良事件。基于我们的研究结果,对于STS患者的帕唑帕尼治疗,似乎尽可能维持可耐受的高剂量强度——至少在最初12周内——可能是更好的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bf8/6352274/f2b020da11e5/jcm-08-00060-g001.jpg

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