Preventive effect of kampo medicine (hangeshashin-to, TJ-14) plus minocycline against afatinib-induced diarrhea and skin rash in patients with non-small cell lung cancer

Abstract

Masao Ichiki,1 Hiroshi Wataya,2 Kazuhiko Yamada,3 Nobuko Tsuruta,4 Hiroaki Takeoka,1 Yusuke Okayama,1 Jun Sasaki,1 Tomoaki Hoshino3 1Department of Respiratory Medicine, Clinical Research Institute, National Hospital Organization, Kyushu Medical Center, 2Division of Internal Medicine, Saiseikai Fukuoka General Hospital, Fukuoka City, 3Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University, Kurume City, 4Department of Respiratory Medicine, Hamanomachi Hospital, Fukuoka City, Fukuoka, Japan Purpose: Diarrhea and oral mucositis induced by afatinib can cause devastating quality of life issues for patients undergoing afatinib treatment. Several studies have shown that hangeshashin-to (TJ-14) might be useful for chemotherapy-induced diarrhea and oral mucositis. In this study, we investigated the prophylactic effects of TJ-14 for afatinib-induced diarrhea and oral mucositis and minocycline for afatinib-induced skin rash.Patients and methods: First- and second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors have become the standard first-line treatment in patients with EGFR-mutated non-small cell lung cancer. The incidence of diarrhea was higher with afatinib than with gefitinib, and we conducted a single-arm Phase II study with afatinib. Patients who had previously undergone treatment with afatinib were ineligible. Both TJ-14 (7.5 g/day) and minocycline (100 mg/day) were administered simultaneously from the start of afatinib administration. The primary end point was the incidence of ≥ grade 3 (G3) diarrhea (increase of ≥7 stools/day over baseline) during the first 4 weeks of treatment. The secondary end points were the incidence of ≥ G3 oral mucositis (severe pain interfering with oral intake) and ≥ G3 skin toxicity (severe or medically significant but not immediately life-threatening).Results: A total of 29 patients (nine men and 20 women; median age, 66 years; performance status, 0/1/2: 18/10/1) were enrolled from four centers. Four patients had undergone prior treatment with chemotherapy, including gefitinib or erlotinib. In all, 20 (68.9%) patients and one (3.4%) patient had diarrhea of any grade and ≥ G3, respectively. One (3.4%) patient had ≥ G3 oral mucositis; no patients had ≥ G3 skin rash. A total of 18 (62%) of the 29 patients achieved a partial response.Conclusion: The present study indicated a trend in which TJ-14 reduced the risk of afatinib-induced diarrhea and minocycline reduced the risk of afatinib-induced skin rash. Keywords: epidermal growth factor receptor, hangeshashin-to, afatinib, adverse events

Keywords

• Epidermal growth factor receptor
• Hangeshashin-to
• afatinib
• adverse events