A phase II study of sunitinib in patients with recurrent and/or metastatic non-nasopharyngeal head and neck cancer
A phase II study of sunitinib in patients with recurrent and/or metastatic non-nasopharyngeal head and neck cancer
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DOI：
10.1007/s00280-009-1070-1
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发表时间：
2010-03-01
影响因子：
3
通讯作者：
Marselos, Marios
中科院分区：
文献类型：
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作者：
Fountzilas, George;Fragkoulidi, Anna;Marselos, Marios
复发性和/或转移性头颈部鳞状细胞癌（RM-SCCHN）患者预后严重。对这种不治之症的新药开发的需求尚未得到满足。血管生成是SCCHN的一个重要生物学过程。因此，我们评估了舒尼替尼（一种针对多种受体的口服酪氨酸激酶抑制剂）在RM-SCCHN患者中的活性和安全性。17例患者接受舒尼替尼治疗，每天50mg，为期4周，随后休息2周。采用有效的液相色谱-串联质谱法测定舒尼替尼和SU012662的血浆水平，并将药代动力学数据拟合为非区室分析。总共进行了28个6周周期的舒尼替尼治疗（中位数为2个周期）。只有3名患者表现出病情稳定；因此，由于无效，研究不得不提前终止。除疲劳外，3级毒性很少发生。其他经常报道的副作用是皮肤变色、中性粒细胞减少和血小板减少。7例患者报告了10种不同的出血并发症。在治疗的第一天，舒尼替尼的平均最大浓度（C (max)）为38.98 (+/- 22.66)ng/ml， SU012662为11.12 (+/- 24.57)ng/ml。结果表明，SU012662的半衰期比母药舒尼替尼更长，分布体积更大。所有检测的生物标志物均不具有任何预后价值。根据我们的研究结果，舒尼替尼单药治疗在RM-SCCHN中没有被证明是有效的，并且不需要进一步开发该药物用于该适应症。
Patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN) bear a grave prognosis. There are unmet needs for the development of novel agents for this incurable disease. Angiogenesis is an important biological process in SCCHN. We, therefore, evaluated the activity and safety of sunitinib, an oral tyrosine kinase inhibitor that targets multiple receptors, in patients with RM-SCCHN.Seventeen patients were treated with sunitinib 50 mg per day administrated in 4-week cycles followed by a rest period of 2 weeks. Sunitinib and SU012662 plasma levels were determined based on a validated liquid chromatography-tandem mass spectrometry method and pharmacokinetic data were fitted in a non-compartmental analysis.Totally, 28 6-week cycles of treatment with sunitinib were administered (median, 2 cycles). Only three patients demonstrated stabilization of the disease; therefore, the study had to be terminated prematurely due to futility. Grade 3 toxicities, apart from fatigue, were infrequent. Other frequently reported side effects were skin discoloration, neutropenia, and thrombocytopenia. Ten various bleeding complications were reported in seven patients. Mean maximum concentrations (C (max)) were reached during the first day of treatment for sunitinib at 38.98 (+/- 22.66) ng/ml and for SU012662 at 11.12 (+/- 24.57) ng/ml. Our results showed that SU012662 has a longer half-life and a larger volume of distribution than the parent drug sunitinib. None of the biological markers tested was of any prognostic value.According to our findings, sunitinib monotherapy was not proven active in RM-SCCHN, and no further development of the drug in this indication is warranted.