A phase I study of afatinib for patients aged 75 or older with advanced non-small cell lung cancer harboring EGFR mutations

• DOI: 10.1007/s12032-018-1098-3
• Publication Date: 2018-02-08T08:05:41Z
• Authors: Hisashi Tanaka; Kageaki Taima; Yoshihito Tanaka; Masamichi Itoga; Yoshiko Ishioka; Hideyuki Nakagawa; Keisuke Baba; Yukihiro Hasegawa; Shingo Takanashi; Sadatomo Tasaka
• Keywords: Aged, 80 and over; Male; Original Paper; Lung Neoplasms; Dose-Response Relationship, Drug; Maximum Tolerated Dose; Afatinib; Prognosis; 3. Good health; ErbB Receptors; Survival Rate; 03 medical and health sciences; 0302 clinical medicine; Carcinoma, Non-Small-Cell Lung; Mutation; Quinazolines; Humans; Female; Aged; Follow-Up Studies

This phase I trial was conducted to determine the maximum tolerated dose (MTD) and recommended dose of afatinib for phase II trial in elderly patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. The study used a standard 3 + 3 dose escalation design. Patients aged 75 years or older with advanced NSCLC harboring EGFR mutations were enrolled. The doses of afatinib, which were given once daily, were planned as follows: level 1, 20 mg/day; level 2, 30 mg/day; level 3, 40 mg/day. Dose-limiting toxicity (DLT) was defined as grade 4 hematologic, persistent grade > 2 diarrhea for > 2 days despite concomitant medications or grade 3 non-hematologic toxicity. DLT was evaluated during day 1-28. Fifteen patients were enrolled. Patient characteristics were: male/female 3/12; median age 79 (range 75-87); PS 0/1, 2/13. Six patients have been treated at levels 1 and 3, and three patients at level 2. At level 1, one of six patients experienced grade 3 rush, grade 3 anorexia, and grade 3 infection as DLTs. At level 2, none of three patients experienced a DLT. At level 3, two patients developed grade 3 diarrhea, one of whom also experienced grade 3 anorexia. Most frequent adverse events of any grade were diarrhea, paronychia, rush, and nausea. Most patients at level 2 and 3 required dose reduction in 3 months. MTD was defined as 40 mg/day, and recommended dose for phase II study in elderly patients was 30 mg/day.