%0 Journal Article %A SATOSHI WATANABE %A OU YAMAGUCHI %A AI MASUMOTO %A YURI MAENO %A YOSUKE KAWASHIMA %A OSAMU ISHIMOTO %A SHUNICHI SUGAWARA %A HIROHISA YOSHIZAWA %A TOSHIAKI KIKUCHI %A TOSHIHIRO NUKIWA %A KUNIHIKO KOBAYASHI %T Phase I Study Evaluating the Combination of Afatinib with Carboplatin and Pemetrexed After First-line EGFR-TKIs %D 2018 %R 10.21873/anticanres.12776 %J Anticancer Research %P 4699-4704 %V 38 %N 8 %X Background/Aim: Promising reports have described the combination of first-generation epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) with carboplatin plus pemetrexed or bevacizumab. However, no analysis of afatinib with platinum-doublet chemotherapies has been performed. Patients and Methods: We evaluated the safety and antitumor efficacy of afatinib combined with carboplatin and pemetrexed in EGFR-mutated non-small-cell lung cancer (NSCLC) patients who progressed during first-generation EGFR-TKIs. Results: Ten patients received 20 or 30 mg/day afatinib with carboplatin (area under the curve, 5) and pemetrexed (500 mg/m2). Dose-limiting toxicities included delay of afatinib ≥14 days, grade 3 diarrhea, grade 3 hypokalemia, grade 3 serum amylase increase and grade 4 thrombocytopenia. The recommended dose of afatinib was 20 mg/day in this combination therapy. Overall response rate was 30% and median progression-free survival was 13.7 months. Conclusion: This is the first study to investigate the combination of afatinib, carboplatin and pemetrexed. At the recommended dose, this combination was well tolerated and had a good clinical efficacy. %U https://ar.iiarjournals.org/content/anticanres/38/8/4699.full.pdf