Juarez Tiffany M, Gill Jaya M, Heng Annie, Carrillo Jose A, Wagle Naveed, Nomura Natsuko, Nguyen Minhdan, Truong Judy, Dobrawa Lucia, Sivakumar Walavan, Barkhoudarian Garni, Kelly Daniel F, Kesari Santosh
Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neuro-Oncology, Santa Monica, California, USA.
Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neurosurgery, Santa Monica, California, USA.
Neurooncol Adv. 2024 Mar 30;6(1):vdae049. doi: 10.1093/noajnl/vdae049. eCollection 2024 Jan-Dec.
Afatinib (BIBW2992; Gilotrif®) is a selective and irreversible inhibitor of the epidermal growth factor receptor (ErbB; EGFR) family. It inhibits EGFR, HER2, and HER4 phosphorylation, resulting in tumor growth inhibition and regression. This phase I dose-escalation trial of pulsatile afatinib examined the safety, drug penetration into the central nervous system, preliminary antitumor activity, and recommended phase II dose in patients with progressive or recurrent brain cancers.
Afatinib was taken orally once every 4 days or once every 7 days depending on dose cohort, until disease progression or unacceptable toxicity.
A total of 24 patients received the investigational agent and were evaluable for safety analyses, and 21 patients were evaluable for efficacy. Dosing was administered at 80 mg every 4 days, 120 mg every 4 days, 180 mg every 4 days, or 280 mg every 7 days. A recommended phase II dose of pulsatile afatinib was established at 280 mg every 7 days as there were no dose-limiting toxicities in any of the dosing cohorts and all toxicities were deemed manageable. The most common drug-related toxicities were diarrhea, rash, nausea, vomiting, fatigue, stomatitis, pruritus, and limb edema. Out of the 21 patients evaluable for efficacy, 2 patients (9.5%) exhibited partial response based on Response Assessment in Neuro-Oncology criteria and disease stabilization was seen in 3 patients (14.3%).
Afatinib taken orally was safe and well-tolerated up to 280 mg every 7 days in brain cancer patients.
阿法替尼（BIBW2992；吉泰瑞®）是一种表皮生长因子受体（ErbB；EGFR）家族的选择性不可逆抑制剂。它抑制EGFR、HER2和HER4磷酸化，从而抑制肿瘤生长并使其消退。这项阿法替尼脉冲给药的I期剂量递增试验研究了进行性或复发性脑癌患者的安全性、药物向中枢神经系统的渗透、初步抗肿瘤活性以及推荐的II期剂量。
根据剂量组，阿法替尼每4天口服一次或每7天口服一次，直至疾病进展或出现不可接受的毒性。
共有24例患者接受了研究药物治疗并可进行安全性分析，21例患者可进行疗效评估。给药剂量为每4天80mg、每4天120mg、每4天180mg或每7天280mg。由于任何剂量组均未出现剂量限制性毒性且所有毒性均被认为可控，因此确定阿法替尼脉冲给药的推荐II期剂量为每7天280mg。最常见的药物相关毒性为腹泻、皮疹、恶心、呕吐、疲劳、口腔炎、瘙痒和肢体水肿。在21例可评估疗效的患者中，根据神经肿瘤学疗效评估标准，2例患者（9.5%）出现部分缓解，3例患者（14.3%）病情稳定。
脑癌患者口服阿法替尼，每7天服用280mg时安全且耐受性良好。
