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01-08-2019 | Alopecia | Clinical trial

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

Authors: Noriko Sagawa, 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

Published in: Breast Cancer Research and Treatment | Issue 3/2019

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.

Lemieux J, Maunsell E, Provencher L (2008) Chemotherapy-induced alopecia and effects on quality of life among women with breast cancer: a literature review. Psycho-Oncology 17:317–328. https://doi.org/10.1002/pon.1245 CrossRefPubMed

Moebus V, Jackisch C, Lueck HJ et al (2010) Intense dose-dense sequential chemotherapy with epirubicin, paclitaxel, and cyclophosphamide compared with conventionally scheduled chemotherapy in high-risk primary breast cancer: mature results of an AGO phase III study. J Clin Oncol 28:2874–2880. https://doi.org/10.1200/JCO.2009.24.7643 CrossRefPubMed

D’Agostini F, Bagnasco M, Giunciuglio D et al (1998) Inhibition by oral N-acetylcysteine of doxorubicin-induced clastogenicity and alopecia, and prevention of primary tumors and lung micrometastases in mice. Int J Oncol 13:217–224PubMed

Schilli MB, Paus R, Menrad A (1998) Reduction of intrafollicular apoptosis in chemotherapy-induced alopecia by topical calcitriol-analogs. J Invest Dermatol 111:598–604. https://doi.org/10.1046/j.1523-1747.1998.00350.x CrossRefPubMed

Botchkarev VA (2003) Molecular mechanisms of chemotherapy-induced hair loss. J Investig Dermatol Symp Proc 8:72–75. https://doi.org/10.1046/j.1523-1747.2003.12175.x CrossRefPubMed

Hiratsuka T, Inomata M, Kono Y et al (2013) DHLTauZnNa, a newly synthesized alpha-lipoic acid derivative, induces autophagy in human colorectal cancer cells. Oncol Rep 29:2140–2146. https://doi.org/10.3892/or.2013.2394 CrossRefPubMed

Kono Y, Inomata M, Hagiwara S et al (2012) Antiproliferative effects of a new alpha-lipoic acid derivative, DHL-HisZnNa, in HT29 human colon cancer cells in vitro. Expert Opin Ther Targets 16(Suppl 1):S103–S109. https://doi.org/10.1517/14728222.2011.640320 CrossRefPubMed

Hagiwara S, Uchida T, Koga H et al (2011) The alpha-lipoic acid derivative sodium zinc dihydrolipoylhistidinate reduces chemotherapy-induced alopecia in a rat model: a pilot study. Surg Today 41:693–697. https://doi.org/10.1007/s00595-010-4481-z CrossRefPubMed

Chon SY, Champion RW, Geddes ER et al (2012) Chemotherapy-induced alopecia. J Am Acad Dermatol 67:e37–e47. https://doi.org/10.1016/j.jaad.2011.02.026 CrossRefPubMed

10.

van den Hurk CJ, van den Akker-van Marle ME, Breed WP et al (2014) Cost-effectiveness analysis of scalp cooling to reduce chemotherapy-induced alopecia. Acta Oncol 53:80–87. https://doi.org/10.3109/0284186X.2013.794955 CrossRefPubMed

11.

Duvic M, Lemak NA, Valero V et al (1996) A randomized trial of minoxidil in chemotherapy-induced alopecia. J Am Acad Dermatol 35:74–78. https://doi.org/10.1016/s0190-9622(96)90500-9 CrossRefPubMed

12.

Cho J, Choi EK, Kim IR et al (2014) Development and validation of Chemotherapy-induced Alopecia Distress Scale (CADS) for breast cancer patients. Ann Oncol 25:346–351. https://doi.org/10.1093/annonc/mdt476 CrossRefPubMed

13.

D’Agostini F, Fiallo P, Ghio M et al (2013) Chemoprevention of doxorubicin-induced alopecia in mice by dietary administration of l-cystine and vitamin B6. Arch Dermatol Res 305:25–34. https://doi.org/10.1007/s00403-012-1253-1 CrossRefPubMed

14.

Martin-Jimenez M, Diaz-Rubio E, Gonzalez Larriba JL et al (1986) Failure of high-dose tocopherol to prevent alopecia induced by doxorubicin. N Engl J Med 315:894–895. https://doi.org/10.1056/NEJM198610023151416 CrossRefPubMed

15.

Gardani G, Cerrone R, Biella C et al (2007) A case–control study of Panicum Miliaceum in the treatment of cancer chemotherapy-induced alopecia. Minerva Med 98:661–664PubMed

16.

Prevezas C, Matard B, Pinquier L et al (2009) Irreversible and severe alopecia following docetaxel or paclitaxel cytotoxic therapy for breast cancer. Br J Dermatol 160:883–885CrossRefPubMed

17.

Kluger N, Jacot W, Frouin E et al (2012) Permanent scalp alopecia related to breast cancer chemotherapy by sequential fluorouracil/epirubicin/cyclophosphamide (FEC) and docetaxel: a prospective study of 20 patients. Ann Oncol 23:2879–2884. https://doi.org/10.1093/annonc/mds095 CrossRefPubMed

18.

Fonia A, Cota C, Setterfield JF et al (2017) Permanent alopecia in patients with breast cancer after taxane chemotherapy and adjuvant hormonal therapy: Clinicopathologic findings in a cohort of 10 patients. J Am Acad Dermatol 76:948–957. https://doi.org/10.1016/j.jaad.2016.12.027 CrossRefPubMed

19.

Shin H, Jo SJ, Kim DH et al (2015) Efficacy of interventions for prevention of chemotherapy-induced alopecia: a systematic review and meta-analysis. Int J Cancer 136:E442–E454. https://doi.org/10.1002/ijc.29115 CrossRef

20.

Nangia J, Wang T, Osborne C et al (2017) Effect of a scalp cooling device on alopecia in women undergoing chemotherapy for breast cancer: the SCALP Randomized Clinical Trial. JAMA 317:596–605. https://doi.org/10.1001/jama.2016.20939 CrossRefPubMed

21.

Friedrichs K, Carstensen MH (2014) Successful reduction of alopecia induced by anthracycline and taxane containing adjuvant chemotherapy in breast cancer—clinical evaluation of sensor-controlled scalp cooling. SpringerPlus 3:500. https://doi.org/10.1186/2193-1801-3-500 CrossRefPubMedPubMedCentral

22.

Bulow J, Friberg L, Gaardsting O et al (1985) Frontal subcutaneous blood flow, and epi- and subcutaneous temperatures during scalp cooling in normal man. Scand J Clin Lab Invest 45:505–508CrossRefPubMed

23.

Al-Tameemi W, Dunnill C, Hussain O et al (2014) Use of in vitro human keratinocyte models to study the effect of cooling on chemotherapy drug-induced cytotoxicity. Toxicol In Vitro 28:1366–1376. https://doi.org/10.1016/j.tiv.2014.07.011 CrossRefPubMed

24.

Mols F, van den Hurk CJ, Vingerhoets AJ et al (2009) Scalp cooling to prevent chemotherapy-induced hair loss: practical and clinical considerations. Support Care Cancer 17:181–189. https://doi.org/10.1007/s00520-008-0475-4 CrossRefPubMed

Title: The utility of DHL-HisZnNa, a novel antioxidant, against anticancer agent-induced alopecia in breast cancer patients: a multicenter phase II clinical trial
Authors: Noriko Sagawa
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
Publication date: 01-08-2019
Publisher: Springer US
Keywords: Alopecia
Breast Cancer
Breast Cancer
Cytostatic Therapy
Published in: Breast Cancer Research and Treatment / Issue 3/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05164-5

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