The utility of DHL-HisZnNa, a novel antioxidant, against anticancer agent-induced alopecia in breast cancer patients: a multicenter phase II clinical trial

• Published in: Breast cancer research and treatment 2019-08, Vol.176 (3), p.625-630
• Main Authors: Sagawa, Noriko, Ohno, Shinji, Hiratsuka, Takahiro, Kondo, Naoto, Iwata, Hiroji, Bando, Hiroko, Ohyama, Tetsuji, Ishida, Mayumi, Kono, Yohei, Nakajima, Kentaro, Empuku, Shinichiro, Nishikawa, Setsuko, Irie, Yoshiko, Inomata, Masafumi, Kitano, Seigo
• Format: Article
• Language: English
• Subjects: Adjuvant treatment; Adult; Aged; Aged, 80 and over; Alopecia; Alopecia - diagnosis; Alopecia - drug therapy; Alopecia - etiology; Antimitotic agents; Antineoplastic agents; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic drugs; Antioxidants; Antioxidants - administration & dosage; Antioxidants - chemistry; Antioxidants - therapeutic use; Antitumor agents; Baldness; Breast cancer; Breast Neoplasms - complications; Breast Neoplasms - diagnosis; Breast Neoplasms - drug therapy; Cancer; Cancer patients; Cancer research; Cancer therapies; Chemotherapy; Clinical Trial; Clinical trials; Combined Modality Therapy; Coordination Complexes - administration & dosage; Coordination Complexes - chemistry; Coordination Complexes - therapeutic use; Female; Humans; Lipoic acid; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Middle Aged; Molecular Structure; Oncology; Patients; Product development; Scalp; Sodium; Thioctic Acid - administration & dosage; Thioctic Acid - analogs & derivatives; Thioctic Acid - chemistry; Thioctic Acid - therapeutic use; Treatment Outcome; Young Adult
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-019-05164-5

Purpose Chemotherapy-induced alopecia (CIA) is a distressing adverse effect of anticancer drugs; however, there are currently no mechanisms to completely prevent CIA. In this study, we performed a clinical trial to examine whether sodium N -(dihydrolipoyl)-l-histidinate zinc complex (DHL-HisZnNa), an alpha-lipoic acid derivative, prevents CIA in patients with breast cancer. Methods Between July 2014 and May 2015, we performed a multi-center, single arm, clinical trial involving 103 breast cancer patients who received adjuvant chemotherapy at three medical institutions in Japan. During chemotherapy, a lotion containing 1% DHL-HisZnNa was applied daily to the patients’ scalps. The primary endpoint was the incidence of grade 2 alopecia; the secondary endpoints were the duration of grade 2 alopecia, alopecia-related symptoms, and drug-related adverse events. Alopecia was evaluated by three independent reviewers using head photographs taken from four angles. Results Safety analysis was performed for 101 patients who started the protocol therapy. After excluding one patient who experienced disease progression during treatment, 100 patients who received at least two courses of chemotherapy underwent efficacy analysis. All original 101 patients developed grade 2 alopecia, the median durations of which were 119 days (112–133 days) and 203 days (196–212 days) in the groups treated with four and eight courses of chemotherapy, respectively. Mild or moderate adverse events potentially related to DHL-HisZnNa were observed in 11 patients. Alopecia-related symptoms were observed in 53 patients (52%). Conclusions The application of 1% DHL-HisZnNa to the scalp did not prevent CIA. However, this drug may promote recovery from CIA. Trial registration number: UMIN000014840.