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

  • Noriko SagawaEmail author
  • Shinji Ohno
  • Takahiro Hiratsuka
  • Naoto Kondo
  • Hiroji Iwata
  • Hiroko Bando
  • Tetsuji Ohyama
  • Mayumi Ishida
  • Yohei Kono
  • Kentaro Nakajima
  • Shinichiro Empuku
  • Setsuko Nishikawa
  • Yoshiko Irie
  • Masafumi Inomata
  • Seigo Kitano
Clinical trial
  • 121 Downloads

Abstract

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.

Keywords

Alopecia Antioxidants Chemotherapy DHL-HisZnNa 

Abbreviations

CIA

Chemotherapy-induced alopecia

CTCAE

Common Toxicity Criteria for Adverse Events

DHL-HisZnNa

Sodium N-(dihydrolipoyl)-l-histidinate zinc complex

Notes

Acknowledgements

We would like to express our sincere gratitude to Ms. C. Tomimatsu and Ms. Y. Aso of the Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, who did paperwork for the clinical trial; we also thank Drs. K. Kuroi, S. Shimizu, and T. Takano who are the members of the independent image analysis committee.

Funding

This research was funded by Research and Development Fund from Institute for Innovative Collaboration Promotion, Oita University.

Compliance with ethical standards

Conflict of interest

Oita University received Oita University Aderans Company Limited Collaboration Research Fee.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Noriko Sagawa
    • 1
    Email author
  • Shinji Ohno
    • 2
    • 3
  • Takahiro Hiratsuka
    • 1
  • Naoto Kondo
    • 4
  • Hiroji Iwata
    • 4
  • Hiroko Bando
    • 5
  • Tetsuji Ohyama
    • 6
  • Mayumi Ishida
    • 2
  • Yohei Kono
    • 1
  • Kentaro Nakajima
    • 1
  • Shinichiro Empuku
    • 1
  • Setsuko Nishikawa
    • 4
  • Yoshiko Irie
    • 7
  • Masafumi Inomata
    • 1
  • Seigo Kitano
    • 8
  1. 1.Department of Gastroenterological and Pediatric Surgery, Faculty of MedicineOita UniversityOitaJapan
  2. 2.Department of Breast OncologyNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
  3. 3.Breast Oncology CenterCancer Institute Hospital of the Japanese Foundation for Cancer ResearchTokyoJapan
  4. 4.Department of Breast OncologyAichi Cancer CenterNagoyaJapan
  5. 5.Department of Breast and Endocrine Surgery, Faculty of MedicineUniversity of TsukubaTsukubaJapan
  6. 6.Biostatistics CenterKurume UniversityKurumeJapan
  7. 7.Department of NursingUniversity of Tsukuba HospitalTsukubaJapan
  8. 8.Oita UniversityOitaJapan

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