In vitro and in vivo efficacy of afatinib as a single agent or in combination with gemcitabine for the treatment of nasopharyngeal carcinoma.
OBJECTIVE
Epidermal growth factor receptor (EGFR) is usually overexpressed in nasopharyngeal carcinoma (NPC). We tested the antitumor effects of irreversible ErbB family inhibitor afatinib on human NPC using in vitro and in vivo models.


METHODS
The effect of afatinib on NPC cells was evaluated using the Cell Counting Kit 8 (CCK8) assay, flow cytometry, and Western blot analyses. The effect of afatinib, as either a single agent or in combination with gemcitabine (GEM), on tumor growth was determined using NPC tumor xenografts in mice.


RESULTS
Afatinib inhibited cell growth in all three NPC cell lines tested in a dose-dependent manner. Afatinib promoted cell cycle arrest at the S and G2/M phases, and it significantly inhibited epidermal growth factor (EGF)-induced activation of EGFR and its downstream signaling factors. Co-treatment with afatinib and GEM more effectively inhibited tumor growth than either drug alone but was associated with increased toxicity.


CONCLUSIONS
Afatinib induced cell cycle arrest and inhibited the proliferation of NPC cell lines. Afatinib in combination with GEM demonstrated significant antitumor effect in an NPC xenograft model. The administration of afatinib with GEM in NPC needs to be modified in order to be effective and tolerable.
Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
Cong
C
Xue
Department of Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
Ying
Y
Tian
Department of Medical Oncology, The First Affiliated Hospital of Guangzhou Traditional Chinese Medicine University, Guangzhou, Guangdong, People's Republic of China.
Jing
J
Zhang
Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
Yuanyuan
Y
Zhao
Department of Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
Jianhua
J
Zhan
Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
Wenfeng
W
Fang
Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
Li
L
Zhang
D000077716:Afatinib; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002277:Carcinoma; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D011799:Quinazolines / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D011799:Quinazolines; D003841:Deoxycytidine; D000077716:Afatinib; D000093542:Gemcitabine
EGFR; afatinib; gemcitabine; nasopharyngeal carcinoma; preclinical