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A phase II study of HMB/Arg/Gln against oral mucositis induced by chemoradiotherapy for patients with head and neck cancer

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Abstract

Purpose

This phase II trial assessed the clinical benefit of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine (HMB/Arg/Gln) for preventing chemoradiotherapy (CRT)-induced oral mucositis (OM) in patients with head and neck cancer (HNC).

Methods

Patients with HNC receiving definitive or postoperative cisplatin-based CRT were enrolled. HMB/Arg/Gln was administered orally or per percutaneous endoscopic gastrostomy from the first day of CRT up to its completion. All patients received opioid-based pain control and oral care programs that we previously reported. The primary endpoint was the incidence of grade ≥ 3 OM (functional/symptomatic) according to the Common Terminology Criteria of Adverse Events version 3.0. Quality of life (EORTC QLQ-C30/PROMS) at baseline and upon radiotherapy at a dosage of 50 Gy were assessed.

Results

Thirty-five patients with HNC were enrolled. Sixteen of them (45.7%) developed grade ≥ 3 OM (i.e., functional/symptomatic). The incidence of grade ≤ 1 OM (functional/symptomatic) was 51.5% at 2 weeks and 82.9% at 4 weeks after radiotherapy completion. Clinical examination revealed that 10 patients (28.6%) developed grade ≥ 3 OM. The incidence of grade ≤ 1 OM (clinical exam) was 80.0% at 2 weeks and 100% at 4 weeks after radiotherapy completion. Adverse events related to HMB/Arg/Gln were an increase in blood urea nitrogen and diarrhea, but were easily managed.

Conclusions

The addition of HMB/Arg/Gln to opioid-based pain control and oral care programs was feasible but still insufficient at reducing the incidence of CRT-induced severe OM. However, the benefit of HMB/Arg/Gln should not be neglected given the findings of clinical examinations and the rapid recovery from severe OM.

Trial registration

UMIN000016453

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Acknowledgements

The authors thank Ms. Marina Kobayashi for data collection.

Funding

This study was supported by the Public Interest Incorporated Foundation - Shizuoka Industrial Foundation - Pharma Valley Center. The funders had no role regarding study design, data analysis, and the decision to publish or preparation of the manuscript.

Author information

Authors and Affiliations

  1. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan

    Tomoya Yokota, Satoshi Hamauchi & Yukio Yoshida

  2. Division of Dental and Oral Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan

    Takashi Yurikusa & Miho Suzuki

  3. Division of Nutrition, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan

    Aiko Yamashita

  4. Division of Radiation Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan

    Hirofumi Ogawa & Tsuyoshi Onoe

  5. Clinical Trial Coordination Office, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan

    Keita Mori

  6. Division of Head and Neck Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan

    Tetsuro Onitsuka

Authors
  1. Tomoya Yokota
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  2. Satoshi Hamauchi
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  3. Yukio Yoshida
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  4. Takashi Yurikusa
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  5. Miho Suzuki
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  6. Aiko Yamashita
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  7. Hirofumi Ogawa
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  8. Tsuyoshi Onoe
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  9. Keita Mori
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  10. Tetsuro Onitsuka
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Corresponding author

Correspondence to Tomoya Yokota.

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Conflict of interest

Tomoya Yokota serves in an advisory role for AstraZeneca, Merck Serono, Bayer, Ono Pharma CO., Ltd., and Bristol-Myers Squibb, and has received lecture fees from Merck Serono, Ono Pharma CO., Ltd., Eisai, Bayer, and Bristol-Myers Squibb.

Electronic supplementary material

Supplementary Fig. 1

The effect of HMB/Arg/Gln supplementation on blood urea nitrogen (mg/dL). *, p<0.01. Bar: standard deviation. (GIF 98 kb)

high resolution image (TIFF 72 kb)

Supplementary Fig. 2

Quality of life and symptom burden. The mean values of functional and symptom scales in QLQ-C30 are shown at baseline, at the time of radiotherapy administration of a dosage of 50 Gy, and 4 weeks after radiotherapy completion. All scales range from 0 to 100 and were scored such that higher values indicate better functioning or higher symptom burden. (GIF 118 kb)

High resolution image (TIFF 67 kb)

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high Resolution image (TIFF 124 kb)

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High resolution image (TIFF 66 kb)

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High resolution image (TIFF 98 kb)

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High resolution image (TIFF 82 kb)

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Yokota, T., Hamauchi, S., Yoshida, Y. et al. A phase II study of HMB/Arg/Gln against oral mucositis induced by chemoradiotherapy for patients with head and neck cancer. Support Care Cancer 26, 3241–3248 (2018). https://doi.org/10.1007/s00520-018-4175-4

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  • DOI: https://doi.org/10.1007/s00520-018-4175-4

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