Ayano Goto1, Yuichi Ozawa2, Keigo Koda3, Daisuke Akahori4, Takashi Koyauchi5, Yusuke Amano6, Takuya Kakutani7, Yoshiko Sato8, Hirotsugu Hasegawa9, Takashi Matsui10, Koshi Yokomura11, Takafumi Suda12. 1. Department of Respiratory Medicine, Respiratory Disease Center, Seirei Mikatahara General Hospital, 3453 Mikatahara, Kita Ward, Hamamatsu, Shizuoka 433-8558, Japan. Electronic address: a.goto@sis.seirei.or.jp. 2. Department of Respiratory Medicine, Respiratory Disease Center, Seirei Mikatahara General Hospital, 3453 Mikatahara, Kita Ward, Hamamatsu, Shizuoka 433-8558, Japan. Electronic address: u1.ozawa@sis.seirei.or.jp. 3. Department of Respiratory Medicine, Respiratory Disease Center, Seirei Mikatahara General Hospital, 3453 Mikatahara, Kita Ward, Hamamatsu, Shizuoka 433-8558, Japan. Electronic address: koudakeigokouda@yahoo.co.jp. 4. Department of Respiratory Medicine, Respiratory Disease Center, Seirei Mikatahara General Hospital, 3453 Mikatahara, Kita Ward, Hamamatsu, Shizuoka 433-8558, Japan. Electronic address: daisuke_a_813@yahoo.co.jp. 5. Department of Respiratory Medicine, Respiratory Disease Center, Seirei Mikatahara General Hospital, 3453 Mikatahara, Kita Ward, Hamamatsu, Shizuoka 433-8558, Japan. Electronic address: tak.koyauchhi@gmail.com. 6. Department of Respiratory Medicine, Respiratory Disease Center, Seirei Mikatahara General Hospital, 3453 Mikatahara, Kita Ward, Hamamatsu, Shizuoka 433-8558, Japan. Electronic address: soccerya0706@yahoo.co. 7. Department of Respiratory Medicine, Respiratory Disease Center, Seirei Mikatahara General Hospital, 3453 Mikatahara, Kita Ward, Hamamatsu, Shizuoka 433-8558, Japan. Electronic address: takuya32k@yahoo.co.jp. 8. Department of Respiratory Medicine, Respiratory Disease Center, Seirei Mikatahara General Hospital, 3453 Mikatahara, Kita Ward, Hamamatsu, Shizuoka 433-8558, Japan. Electronic address: yoccherry_o4o5_blossom@i.softbank.jp. 9. Department of Respiratory Medicine, Respiratory Disease Center, Seirei Mikatahara General Hospital, 3453 Mikatahara, Kita Ward, Hamamatsu, Shizuoka 433-8558, Japan. Electronic address: h-hasegawa@sis.seirei.or.jp. 10. Department of Respiratory Medicine, Respiratory Disease Center, Seirei Mikatahara General Hospital, 3453 Mikatahara, Kita Ward, Hamamatsu, Shizuoka 433-8558, Japan. Electronic address: t-matsui@sis.seirei.or.jp. 11. Department of Respiratory Medicine, Respiratory Disease Center, Seirei Mikatahara General Hospital, 3453 Mikatahara, Kita Ward, Hamamatsu, Shizuoka 433-8558, Japan. Electronic address: yo.koshi@sis.seirei.or.jp. 12. Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, Shizuoka 431-3192, Japan. Electronic address: suda@hama-med.ac.jp.
Abstract
BACKGROUND: The management of skin toxicity is crucial for efficient afatinib treatment, but the role of tetracycline class antibiotics (TCs) in managing these rashes is relatively unknown. METHODS: We reviewed the clinical records of patients who were administered afatinib for the treatment of non-small cell lung cancer harboring epidermal growth factor receptor mutations between October 2014 and November 2016. Twenty-five patients, who received TCs for the management of afatinib-related skin disorders, were enrolled. RESULTS: Minocycline was administered orally to participants. Afatinib-related toxic effects, such as rash, diarrhea, and paronychia, were observed in 92%, 92%, and 40% of cases, respectively. Although 24% of diarrhea and 4% of paronychia cases were rated grade 3 or higher, no severe cases of rash were observed during afatinib treatment. Of the 18 afatinib dose reductions, 14 (78%), three (17%), and one (6%) resulted from diarrhea, paronychia, and stomatitis, respectively; no patients required a dose reduction because of rash. When minocycline treatment started, 21 patients (84%) had a rash of grade 1 or less, and three patients had a grade 2 rash. A response to afatinib was observed in 18 patients (72%) and the median duration of afatinib administration was 501 days. An adverse event related to minocycline (grade 1 nausea) was observed in one patient. CONCLUSIONS: A large proportion of the study patients started minocycline before grade 2 rash development and the severity of afatinib-related rash was lower than that previously reported. Oral TCs may be beneficial, especially if started early.
BACKGROUND: The management of skin toxicity is crucial for efficient afatinib treatment, but the role of tetracycline class antibiotics (TCs) in managing these rashes is relatively unknown. METHODS: We reviewed the clinical records of patients who were administered afatinib for the treatment of non-small cell lung cancer harboring epidermal growth factor receptor mutations between October 2014 and November 2016. Twenty-five patients, who received TCs for the management of afatinib-related skin disorders, were enrolled. RESULTS:Minocycline was administered orally to participants. Afatinib-related toxic effects, such as rash, diarrhea, and paronychia, were observed in 92%, 92%, and 40% of cases, respectively. Although 24% of diarrhea and 4% of paronychia cases were rated grade 3 or higher, no severe cases of rash were observed during afatinib treatment. Of the 18 afatinib dose reductions, 14 (78%), three (17%), and one (6%) resulted from diarrhea, paronychia, and stomatitis, respectively; no patients required a dose reduction because of rash. When minocycline treatment started, 21 patients (84%) had a rash of grade 1 or less, and three patients had a grade 2 rash. A response to afatinib was observed in 18 patients (72%) and the median duration of afatinib administration was 501 days. An adverse event related to minocycline (grade 1 nausea) was observed in one patient. CONCLUSIONS: A large proportion of the study patients started minocycline before grade 2 rash development and the severity of afatinib-related rash was lower than that previously reported. Oral TCs may be beneficial, especially if started early.