Chougnet Cecile N, Borget Isabelle, Leboulleux Sophie, de la Fouchardiere Christelle, Bonichon Françoise, Criniere Lise, Niccoli Patricia, Bardet Stéphane, Schneegans Olivier, Zanetta Sylvie, Schvartz Claire, Drui Delphine, Chauffert Bruno, Rohmer Vincent, Schlumberger Martin
1 Department of Nuclear Medicine, Hôpital Saint Louis , Paris, France .
Thyroid. 2015 Apr;25(4):386-91. doi: 10.1089/thy.2014.0361. Epub 2015 Feb 18.
A randomized phase III trial demonstrated that vandetanib treatment is effective in patients with metastatic medullary thyroid cancer (MTC), leading to regulatory approval, but its use may be associated with toxicities that require specific monitoring and management. The objective of the present study performed in France was to describe the toxicity profile and efficacy of vandetanib treatment when given outside any trial.
Sixty-eight patients were treated with vandetanib in the frame of a temporary use authorization (ATU) in France from August 2010 to February 2012, when the drug was available on request for patients with locally advanced or metastatic MTC. Patients were registered by the French health authorities, and characteristics, treatment parameters, toxicity profile, and efficacy were retrospectively reviewed. Eight patients were excluded from the analysis because vandetanib treatment was not administered (n=3), had been given in a trial before ATU (n=3), or was given for a non-MTC cancer (n=2).
Data from the 60 MTC patients were analyzed. Mean age was 58 years (range 11-83 years), 39 patients were male, and six had hereditary MTC. Fifty-six (93%) had metastatic disease in the mediastinum (82%), bones (65%), liver (53%), or lung (53%), and four had only locally advanced disease. At the time of study evaluation, with a median follow-up of 20 months and a median duration of treatment of 9.7 months (range 0.3-36 months), 15 patients were continuing vandetanib treatment (range 18-36 months). Median progression-free survival was 16.1 months. Twenty-five patients discontinued treatment for disease progression (range 0.3-29 months). Best tumor response was a complete response in one patient, a partial response in 12 (20%), stable disease in 33 (55%), and progression in seven patients (12%). All patients had at least one adverse event (AE) during treatment. The main AEs were skin toxicity, diarrhea, and asthenia. Sixteen patients (27%) discontinued treatment for toxicity, and one patient died from vandetanib-induced cardiac toxicity.
Vandetanib is an effective option for patients with advanced MTC. AEs should be monitored carefully and should be minimized by educating both patients and care providers and by applying symptomatic treatment and dose reduction.
一项随机III期试验表明，凡德他尼治疗对转移性甲状腺髓样癌（MTC）患者有效，并获得了监管部门的批准，但其使用可能会伴有需要特殊监测和管理的毒性反应。在法国开展的本研究的目的是描述凡德他尼在非试验环境下使用时的毒性特征和疗效。
2010年8月至2012年2月期间，法国68例患者在临时使用授权（ATU）框架下接受了凡德他尼治疗，当时该药物可应局部晚期或转移性MTC患者的要求提供。患者由法国卫生当局登记，对其特征、治疗参数、毒性特征和疗效进行回顾性分析。8例患者被排除在分析之外，原因是未接受凡德他尼治疗（n = 3）、在ATU之前的试验中已接受过治疗（n = 3）或用于非MTC癌症（n = 2）。
分析了60例MTC患者的数据。平均年龄为58岁（范围11 - 83岁），39例为男性，6例患有遗传性MTC。56例（93%）有纵隔（82%）、骨骼（65%）、肝脏（53%）或肺部（53%）的转移性疾病，4例仅有局部晚期疾病。在研究评估时，中位随访时间为20个月，中位治疗持续时间为9.7个月（范围0.3 - 36个月），15例患者继续接受凡德他尼治疗（范围18 - 36个月）。中位无进展生存期为16.1个月。25例患者因疾病进展停药（范围0.3 - 29个月）。最佳肿瘤反应为1例完全缓解，12例（20%）部分缓解，33例（55%）病情稳定，7例（12%）进展。所有患者在治疗期间至少发生1次不良事件（AE）。主要AE为皮肤毒性、腹泻和乏力。16例患者（27%）因毒性停药，1例患者死于凡德他尼引起的心脏毒性。
凡德他尼是晚期MTC患者的有效选择。应仔细监测AE，并通过对患者和护理人员进行教育以及采用对症治疗和剂量减少将AE降至最低。
