Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial.
Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial.
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DOI：
10.1016/s1470-2045(14)71181-7
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发表时间：
2015-02
期刊：
影响因子：
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通讯作者：
Giaccone G
中科院分区：
文献类型：
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作者：
Thomas A;Rajan A;Berman A;Tomita Y;Brzezniak C;Lee MJ;Lee S;Ling A;Spittler AJ;Carter CA;Guha U;Wang Y;Szabo E;Meltzer P;Steinberg SM;Trepel JB;Loehrer PJ;Giaccone G
对于铂类化疗失败后的晚期胸腺上皮肿瘤，没有标准的治疗方法。我们研究了口服酪氨酸激酶抑制剂舒尼替尼的活性。在2012年5月15日至2013年10月2日期间，我们在组织学证实的化疗难治性胸腺上皮肿瘤患者中进行了一项开放标签2期试验。如果患者在至少一种含铂化疗方案后出现疾病进展，东部肿瘤协作组体能状态为2或更低，可测量疾病，以及器官功能充足，则符合资格。患者每天口服一次50 mg舒尼替尼，6周为一个周期（即治疗4周，随后2周不治疗），直至肿瘤进展或出现不可接受的毒性作用。主要终点是在任何时间点上经评估的最佳肿瘤缓解，我们在胸腺瘤和胸腺癌队列中分别进行了分析。接受至少一个周期治疗并对其疾病进行重新评估的患者被纳入缓解分析。该试验在ClinicalTrials.gov上注册，编号为NCT 01621568。入组41例患者，其中胸腺癌25例，胸腺瘤16例。1例胸腺癌患者在入组后被视为不合格，未接受方案治疗。在接受治疗的患者中，1例胸腺癌患者因死亡而无法评估。试验中位随访时间为17个月（IQR 14·0-18·4）。在23例可评估的胸腺癌患者中，6例（26%，90% CI 12.1 - 45.3，95% CI 10.2 - 48.4）部分缓解，15例（65%，95% CI 42.7 - 83.6）疾病稳定，2例（9%，1.1 - 28.0）疾病进展。在16例胸腺瘤患者中，1例（6%，95%CI 0.2 - 30.2）部分缓解，12例（75%，47.6 - 92.7）病情稳定，3例（19%，4.1 - 45.7）病情进展。最常见的3级和4级治疗相关不良事件是淋巴细胞减少症（40例患者中有8例[20%]）、疲劳（8例[20%]）和口腔粘膜炎（8例[20%]）。5例（13%）患者左心室射血分数降低，其中3例（8%）为3级事件。3例（8%）患者在治疗期间死亡，其中1例患者死于可能与治疗相关的心脏骤停。舒尼替尼在既往接受过治疗的胸腺癌患者中具有活性。需要进一步的研究来确定潜在的活性生物标志物。国家癌症研究所（癌症治疗评估计划）。
No standard treatments are available for advanced thymic epithelial tumours after failure of platinum-based chemotherapy. We investigated the activity of sunitinib, an orally administered tyrosine kinase inhibitor. Between May 15, 2012, and Oct 2, 2013, we did an open-label phase 2 trial in patients with histologically confirmed chemotherapy-refractory thymic epithelial tumours. Patients were eligible if they had disease progression after at least one previous regimen of platinum-containing chemotherapy, an Eastern Cooperative Oncology Group performance status of two or lower, measurable disease, and adequate organ function. Patients received 50 mg of sunitinib orally once a day, in 6-week cycles (ie, 4 weeks of treatment followed by 2 weeks without treatment), until tumour progression or unacceptable toxic effects arose. The primary endpoint was investigator-assessed best tumour response at any point, which we analysed separately in thymoma and thymic carcinoma cohorts. Patients who had received at least one cycle of treatment and had their disease reassessed were included in the analyses of response. The trial was registered with ClinicalTrials.gov, number NCT01621568. 41 patients were enrolled, 25 with thymic carcinoma and 16 with thymoma. One patient with thymic carcinoma was deemed ineligible after enrolment and did not receive protocol treatment. Of patients who received treatment, one individual with thymic carcinoma was not assessable because she died. Median follow-up on trial was 17 months (IQR 14·0–18·4). Of 23 assessable patients with thymic carcinoma, six (26%, 90% CI 12·1–45·3, 95% CI 10·2–48·4) had partial responses, 15 (65%, 95% CI 42·7–83·6) achieved stable disease, and two (9%, 1·1–28·0) had progressive disease. Of 16 patients with thymoma, one (6%, 95% CI 0·2–30·2) had a partial response, 12 (75%, 47·6–92·7) had stable disease, and three (19%, 4·1–45·7) had progressive disease. The most common grade 3 and 4 treatment-related adverse events were lymphocytopenia (eight [20%] of 40 patients), fatigue (eight [20%]), and oral mucositis (eight [20%]). Five (13%) patients had decreases in left-ventricular ejection fraction, of which three (8%) were grade 3 events. Three (8%) patients died during treatment, including one individual who died of cardiac arrest that was possibly treatment-related. Sunitinib is active in previously treated patients with thymic carcinoma. Further studies are needed to identify potential biomarkers of activity. National Cancer Institute (Cancer Therapy Evaluation Program).