Introduction: Thymoma and thymic carcinoma (TC) are neoplastic diseases with reported chemosensitivity to a broad range of agents. However, because of the rarity of these diseases, few prospective trials have been conducted in patients with advanced thymic malignancies. We conducted a prospective phase II trial to evaluate the clinical activity of pemetrexed, a multitargeted antifolate agent, in previously treated patients with thymoma and TC. Methods: A total of 27 previously treated patients (16 with thymoma and 11 with TC) with advanced, unresectable disease were treated with pemetrexed, 500 mg/m2, intravenously every 3 weeks for a maximum of six cycles or until undue toxicity or progressive disease. All patients received folic acid, vitamin B12, and steroid prophylaxis. Results: The median number of cycles administered was 6 (range 1–6). Nine patients with a total of 14 events had grade 3 toxicities; no grade 4 toxicities were noted. In 26 fully evaluable patients, two complete and three partial responses (according to the Response Evaluation Criteria in Solid Tumors) were documented (all in patients with stage IVA thymoma, except for one partial response with stage IVA TC). A total of 14 patients completed the full six cycles of treatment, 7 patients progressed while undergoing therapy, 5 patients discontinued therapy because of intolerance, and 1 patient discontinued therapy because of progressive Morvan syndrome. The median progression‐free survival time for all patients was 10.6 months (12.1 months for those with thymoma versus 2.9 months for those with TC). With 23 deaths at data cutoff, the median overall survival time was 28.7 months (46.4 months for those with thymoma versus 9.8 months for those with TC). Conclusions: Pemetrexed is an active agent in this heavily pretreated population of patients with recurrent thymic malignancies, especially thymoma.

中文翻译：

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培美曲塞治疗复发性胸腺瘤和胸腺癌患者的 II 期研究

简介：胸腺瘤和胸腺癌 (TC) 是肿瘤性疾病，据报道对多种药物具有化学敏感性。然而，由于这些疾病的罕见性，很少对晚期胸腺恶性肿瘤患者进行前瞻性试验。我们进行了一项前瞻性 II 期试验，以评估培美曲塞（一种多靶点抗叶酸剂）在既往接受过治疗的胸腺瘤和 TC 患者中的临床活性。方法：共有 27 名既往接受过治疗的晚期、不可切除疾病患者（16 名胸腺瘤患者和 11 名 TC 患者）接受培美曲塞 500 mg/m2，每 3 周静脉注射一次，最多 6 个周期，或直至出现过度毒性或疾病进展. 所有患者均接受叶酸、维生素 B12 和类固醇预防。结果：给药周期的中位数为 6（范围 1-6）。共有 14 次事件的 9 名患者出现 3 级毒性；未发现 4 级毒性。在 26 名可完全评估的患者中，记录了 2 个完全缓解和 3 个部分缓解（根据实体瘤中的缓解评估标准）（所有患者均患有 IVA 期胸腺瘤，除了 1 例 IVA TC 期部分缓解）。共有 14 名患者完成了完整的 6 个治疗周期，7 名患者在接受治疗时出现进展，5 名患者因不耐受而停止治疗，1 名患者因进行性 Morvan 综合征而停止治疗。所有患者的中位无进展生存时间为 10.6 个月（胸腺瘤患者为 12.1 个月，TC 患者为 2.9 个月）。数据截止时有 23 人死亡，中位总生存时间为 28.7 个月 (46. 胸腺瘤患者为 4 个月，而 TC 患者为 9.8 个月）。结论：培美曲塞是这种经过大量预处理的复发性胸腺恶性肿瘤，尤其是胸腺瘤患者的活性药物。