Nutting C M, van Herpen C M L, Miah A B, Bhide S A, Machiels J-P, Buter J, Kelly C, de Raucourt D, Harrington K J
Head and Neck Unit, Royal Marsden Hospital and Institute of Cancer Research, London, UK.
Ann Oncol. 2009 Jul;20(7):1275-9. doi: 10.1093/annonc/mdn775. Epub 2009 Feb 26.
Treatment options for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are limited with response rates to cytotoxic chemotherapy of approximately 30% and median survival of 6 months.
In a multicentre phase II study, 32 patients with recurrent or metastatic HNSCC received 3-AP Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), an inhibitor of ribonucleotide reductase, 96 mg/m2, daily for 4 days every 14 days (one cycle). Eligibility criteria required Eastern Cooperative Oncology Group performance status (ECOG PS) of zero to two with a life expectancy of >3 months; one prior chemotherapy regimen was allowed.
Thirty patients were assessable for response and toxicity. Median age was 57 years (range 36-79) and median ECOG PS was one (range 0-2). Thirteen patients had previously been treated with chemotherapy. A total of 130 cycles were administered with a median number of cycles of 3.5 (range 1-8). Mild anaemia (40%), nausea (22%) and fatigue (22%) were commonly reported with G3 and G4 neutropenia documented in 22% and 22%, respectively. Overall response rate was 5.9% (95% confidence interval 0.2% to 28.7%). One patient achieved a partial response, eight had stable disease and 21 progressive disease. Median time to disease progression was 3.9 months.
3-AP Triapine as a single agent, at this dose and schedule, is well tolerated but has only minor activity in the treatment of advanced HNSCC.
复发性或转移性头颈部鳞状细胞癌（HNSCC）的治疗选择有限，细胞毒性化疗的缓解率约为30%，中位生存期为6个月。
在一项多中心II期研究中，32例复发性或转移性HNSCC患者接受核糖核苷酸还原酶抑制剂3-AP曲阿替平（3-氨基吡啶-2-甲醛缩氨基硫脲），剂量为96mg/m²，每14天每日给药1次，共4天（1个周期）。入选标准要求东部肿瘤协作组体能状态（ECOG PS）为0至2，预期寿命>3个月；允许既往接受过一种化疗方案。
30例患者可评估疗效和毒性。中位年龄为57岁（范围36 - 79岁），中位ECOG PS为1（范围0 - 2）。13例患者既往接受过化疗。共给予130个周期，中位周期数为3.5（范围1 - 8）。常见不良反应包括轻度贫血（40%）、恶心（22%）和疲劳（22%），3/4级中性粒细胞减少分别为22%和22%。总体缓解率为5.9%（95%置信区间0.2%至28.7%）。1例患者达到部分缓解，8例病情稳定，21例病情进展。疾病进展的中位时间为3.9个月。
3-AP曲阿替平作为单一药物，按此剂量和给药方案，耐受性良好，但在晚期HNSCC治疗中仅具有轻微活性。
