回复：

礼来公司不建议采用超出当地标签中提供的指导的特定方法来管理培美曲塞相关皮疹。 早期临床试验经验表明，皮疹通常在地塞米松治疗后得到改善，并在停止培美曲塞治疗后消退。^1-3 当前的协议通常允许根据当地标准实践使用支持性护理疗法。⁴

没有成熟的前瞻性临床试验数据来指导对培美曲塞的皮肤反应的详细管理。 认识非常罕见的中毒性表皮坏死松解症(TEN) 事件很重要，因为这些严重症状可能需要不同的治疗。^5-10 否则，根据症状的严重程度，局部或全身皮质类固醇治疗、抗组胺药和支持性措施已用于治疗培美曲塞相关的皮肤反应。^5,6,11-14

参考文献

1. Rusthoven JJ, Eisenhauer E, Butts C, et al; National Cancer Institute of Canada Clinical Trials Group. Multitargeted antifolate LY231514 as first-line chemotherapy for patients with advanced non–small-cell lung cancer: a phase II study. J Clin Oncol. 1999;17(4):1194-1199. http://dx.doi.org/10.1200/jco.1999.17.4.1194

2. Thödtmann R, Depenbrock H, Dumez H, et al. Clinical and pharmacokinetic phase I study of multitargeted antifolate (LY231514) in combination with cisplatin. J Clin Oncol. 1999;17(10):3009-3016. http://dx.doi.org/10.1200/JCO.1999.17.10.3009

3. Clarke SJ, Abratt R, Goedhals L, et al. Phase II trial of pemetrexed disodium (ALIMTA^®, LY231514) in chemotherapy-naïve patients with advanced non-small-cell lung cancer. Ann Oncol. 2002;13(5):737-741. http://dx.doi.org/10.1093/annonc/mdf115

4. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

5. Tummino C, Barlesi F, Tchouhadjian C, et al. Severe cutaneous toxicity after pemetrexed in second line treatment for a refractory non small cell lung cancer [French]. Rev Mal Respir. 2007;24(5):635-638. https://doi.org/10.1016/S0761-8425(07)91133-X

6. Bosch-Barrera J, Gaztañaga M, Ceballos J, et al. Toxic epidermal necrolysis related to pemetrexed and carboplatin with vitamin B12 and folic acid supplementation for advanced non-small cell lung cancer. Onkologie. 2009;32(10):580-584. https://doi.org/10.1159/000232315

7. Scheinpflug K, Menzel C, Koch A, et al. Toxic epidermal necrolysis related to cisplatin and pemetrexed for metastatic non-small cell lung cancer. Onkologie. 2012;35(10):600-603. https://doi.org/10.1159/000342671

8. Then C, von Einem JC, Müller D, et al. Toxic epidermal necrolysis after pemetrexed and cisplatin for non-small cell lung cancer in a patient with Sharp syndrome. Onkologie. 2012;35(12):783-786. https://doi.org/10.1159/000345109

9. Huang JJ, Ma SX, Hou X, et al. Toxic epidermal necrolysis related to AP (pemetrexed plus cisplatin) and gefitinib combination therapy in a patient with metastatic non-small cell lung cancer. Chin J Cancer. 2015;34(2):94-98. https://doi.org/10.5732/cjc.014.10151

10. Aksoy B, Cavusoglu EU. Toxic epidermal necrolysis like antifolate cytotoxic skin reaction due to pemetrexed [Turkish]. Turk J Dermatol. 2018;12(1):68-70. https://doi.org/10.4274/tdd.3066

11. Declercq I, Lievens Y, Verbeken E, Vansteenkiste J. Rash in a patient treated with pemetrexed for relapsed non-small cell lung cancer. J Thorac Oncol. 2008;3(6):662-663. https://doi.org/10.1097/JTO.0b013e318170fcb9

12. Eichhoff G. Slowly developing toxic epidermal necrolysis-like reaction associated with pemetrexed and carboplatin. Ecancermedicalscience. 2020;14:1010. https://doi.org/10.3332/ecancer.2020.1010

13. David E, Krishna R, Ramachandran L, et al. Pemetrexed-associated hyperpigemented skin rash. Am J Ther. Published online February 06, 2020. https://doi.org/10.1097/mjt.0000000000001146

14. Chow KVC, O'Leary C, Paxton-Hall F, et al. Pembrolizumab-induced toxic epidermal necrolysis: case report. Oxf Med Case Rep. 2022;2022(3):112-114. https://dx.doi.org/10.1093/omcr/omac025