Nakano Kenji, Funauchi Yuki, Hayakawa Keiko, Tanizawa Taisuke, Ae Keisuke, Matsumoto Seiichi, Takahashi Shunji
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.
J Clin Med. 2019 Jan 8;8(1):60. doi: 10.3390/jcm8010060.
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.
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。