Effect of HMB/Arg/Gln on the Prevention of Radiation Dermatitis in Head and Neck Cancer Patients Treated with Concurrent Chemoradiotherapy

Imai, Takayuki; Matsuura, Kazuto; Asada, Yukinori; Sagai, Shun; Katagiri, Ken; Ishida, Eiichi; Saito, Daisuke; Sadayasu, Rei; Wada, Hitoshi; Saijo, Shigeru

doi:10.1093/jjco/hyu027

Cited by 27 publications

(38 citation statements)

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“…A previous study reported that β-hydroxy-β-methylbutyrate/arginine/glutamine supplementation was potentially effective in the prevention of radiation dermatitis in patients with HNC, as this supplementation was a protective nutrient with anti-inflammatory effects favoring the healing of inflammatory skin wounds (34).…”

Section: Discussionmentioning

confidence: 99%

Double-blind randomized study of oral glutamine on the management of radio/chemotherapy-induced mucositis and dermatitis in head and neck cancer

Lopez‐Vaquero

Gutiérrez-Bayard

Rodríguez-Ruiz

et al. 2017

Molecular and Clinical Oncology

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Abstract. This randomized clinical trial was designed to determine whether glutamine administration was effective in reducing the incidence and severity of mucositis and dermatitis induced by radiotherapy (RT) or chemoradiotherapy (CHRT) in patients with head and neck cancer (HNC). Fifty patients were randomized to receive orally either L-Glutamine or placebo (25 patients in each arm). In the glutamine-treated group, 10 g of oral glutamine was administered three times daily. The primary endpoint was to compare the appearance of clinical mucositis between groups at the 6th week, according to the Common Terminology Criteria for Adverse Events. Secondary endpoints were: Functional mucositis, mucositis onset, cervicofacial dermatitis, pain, weight loss and assessment of quality of life (according to the M.D. Anderson Symptom Inventory-Head and Neck). In total, 76 and 87.5% developed clinical mucositis in the glutamine and placebo group, respectively. The incidence and severity grade of mucositis at the 6th week did not exhibit statistically significantly differences between the two groups, although it had a higher value in the placebo group. Significant reduction of dermatitis incidence (P=0.038) and severity (P=0.032) was found in the glutamine group. There were no differences in other outcomes such as pain, weight loss and mucositis onset, in treatment parameters including concomitant chemotherapy, radiation dose and previous surgery, or in quality of life. The present study revealed that glutamine provided slight clinical effects compared with placebo in terms of reducing oral mucositis induced by RT or CHRT in patients with HNC at the 6th week; however, the results were not statistically significant. Although the findings suggested a significant benefit in reducing the incidence and severity of dermatitis, further confirmatory studies are required. IntroductionRadiation therapy (RT) and concomitant chemoradiotherapy (CHRT) in patients with head and neck cancer (HNC) are commonly associated with complications such as mucositis and dermatitis in the oral cavity and on the cervicofacial area. Clinically, these adverse effects are able to cause severe pain and odinophagia, increase the risk of infections, skin wounds and inflammatory ulcers, limit deglutition, cause malnutrition and negatively impact the diet and overall quality of life of patients (1). The incidence rate of mucositis varies between 85 and 100%, depending on the cancer treatment regimen, with altered fractionated RT, CHRT or conventional RT (2,3), whereas the incidence of acute dermatitis varies between 7 and 25% (4,5), reaching up to 49% in patients receiving RT in combination with cetuximab (6).Numerous efforts have been made to identify effective agents for preventing and treating mucositis and dermatitis induced by RT or CHRT. Although some standard guidelines for management are available (7,8), reliable and effective treatments are lacking (9). For mucositis, intensive oral care protocols, antimicrobial agents, anti-inflammatory agents, cytopro...

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Section: Discussionmentioning

confidence: 99%

Double-blind randomized study of oral glutamine on the management of radio/chemotherapy-induced mucositis and dermatitis in head and neck cancer

Lopez‐Vaquero

Gutiérrez-Bayard

Rodríguez-Ruiz

et al. 2017

Molecular and Clinical Oncology

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“…A compounding agent containing HMB, glutamine, and arginine effectively protected against chemoradiotherapyinduced dermatitis in head and neck cancer patients (29). This effect may be related to the anti-inflammatory activity of HMB.…”

Section: Discussionmentioning

confidence: 85%

β-Hydroxy-β-methylbutyrate Suppresses NF-ĸB Activation and IL-6 Production in TE-1 Cancer Cells

Miyake

Ogo

Kubota

et al. 2019

In Vivo

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Background/Aim: Stress reactions, especially those related to surgery, cause poor convalescence of cancer patients. β-Hydroxyβ-methylbutyrate (HMB) is known to regulate excessive inflammation in the body. The objective of this work was to investigate the capacity of HMB to suppress activation of nuclear factor-kappa B (NF-ĸB) and production of interleukin-6 (IL-6) in a human esophageal squamous cell carcinoma cell line . Materials and Methods: Cell proliferation was measured using the water-soluble tetrazolium-1 method, while tumor necrosis factor alpha (TNFα)-induced IL-6 production was measured using an enzyme-linked immunosorbent assay (ELISA) assay. Nuclear translocation of NF-ĸB was detected by immunofluorescence staining. Results: HMB did not affect cell proliferation. However, HMB suppressed the TNFα-induced increase in IL-6 production in TE-1 cells by inhibiting NF-ĸB activation. Conclusion: HMB did not influence TE-1 cell proliferation, but inhibited activation of NF-ĸB and IL-6 production. This result may be useful for improving excessive stress reactions during and after surgery.During and after cancer surgery, operative stress can promote tumor metastasis and result in poor prognoses. Notably, stress related to thoraco-laparotomy for esophageal cancer carries an extremely high risk of postoperative complications. Excessive post-surgical stress or postoperative complications, so-called second attacks, cause a cytokine storm that promotes tumor metastasis (surgical oncotaxis). Reported mechanisms underlying surgical oncotaxis include increased adrenal corticoid levels, blood coagulability, immunosuppression, and reactive oxygen species production (1-3).Usually, increased levels of cytokines, such as interleukin-1 (IL-1) or tumor necrosis factor alpha (TNFα), are observed several hours after surgery, followed by increased IL-6 or IL-8 (4, 5). TNFα, a representative inflammatory cytokine secreted in the tumor microenvironment, elicits secretion of other cytokines by activating nuclear factor-kappa B (NF-ĸB) signaling (6). NF-ĸB plays a central role in inflammatory reactions, and is the primary activator of cytokine storms (7,8). Target genes of NF-ĸB include adhesion factors, iNOS (inducible nitric oxide synthase), and other factors (9). Thus, NF-ĸB plays an important role in tumor survival, metastasis, and chemotherapy resistance. NF-ĸB is essential for promoting inflammation-related cancer. This mechanism can significantly impact chemotherapy and cancer-related surgeries (10). Therefore, NF-ĸB regulation is extremely important for cancer therapies.β-hydroxyβ-methylbutyrate (HMB), a metabolite of the branched-chain amino acid leucine that obstructs NF-ĸB (p65) function, has attracted attention for its ability to control excessive inflammatory reactions. HMB reportedly reduces inflammatory cytokine production, apoptosis, and activity of proteolysis-inducing factor (11). Thus, we hypothesized that HMB regulates activation of the ubiquitin-proteasome pathway to control NF-kB activation and excessive inflamm...

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“…Embora essa associação terapêutica seja bené ca na terapia antineoplásica, ela pode aumentar a incidência e a severidade de reações adversas -como a radiodermatite -, sendo importante seu manejo adequado e considerando os impactos negativos das reações no tratamento e na qualidade de vida do paciente 2 .…”

Section: Introductionunclassified

Gel de Chamomilla Recutita para reação de pele em paciente submetido à quimiorradioterapia: relato de caso

Ferreira

Bontempo

Santos

et al. 2017

Estima

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RESUMOO presente relato tem o objetivo de descrever o efeito do gel de Chamomilla recutita (C. recutita) em radiodermatite de paciente submetido à quimiorradioterapia -paciente do sexo masculino, com neoplasia de orofaringe, que fez uso do gel na concentração de 8,35% na região irradiada. A partir da 16ª sessão, o paciente apresentou radiodermatite Grau I, segundo escore Radiation Therapy Oncology Group (RTOG), caracterizada por leve eritema da região irradiada. A graduação foi mantida até o fi nal da radioterapia, com evolução dos sinais apresentados para hipercromia e descamação seca. Os benefícios clínicos da C. recutita na prevenção e no tratamento da radiodermatite evidenciam a importância de estudos experimentais, que possam corroborar os resultados descritos, considerando que a intervenção se mostrou uma alternativa de fácil implementação, fornecendo proteção e conforto ao paciente. DESCRITORES:Radiodermatite. Quimiorradioterapia. Chamomilla. Estomaterapia. ABSTRACTThis report aims at describing the eff ect of Chamomilla recutita (C. recutita) gel in radiodermatitis of a patient submitted to chemoradiotherapy -male patient, with oropharyngeal cancer, that used the gel in the 8.35% concentration in the irradiated region. From the 16 th session, the subject presented Grade I radiodermatitis, according to the RTOG score, characterized by mild erythema in the irradiated region. Graduation was maintained until the end of radiotherapy, with an increase of the signals presented for hyperpigmentation and dry desquamation. The clinical benefi ts of C. recutita in the prevention and treatment of radiodermatitis show the importance of experimental studies that may corroborate the described results, considering that the intervention proved to be an alternative of easy implementation, thus providing protection and comfort to the patient.

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Effect of HMB/Arg/Gln on the Prevention of Radiation Dermatitis in Head and Neck Cancer Patients Treated with Concurrent Chemoradiotherapy

Abstract: Our study indicated that beta-hydroxy-beta-methylbutyrate/arginine/glutamine supplementation was potentially effective in the prevention of radiation dermatitis in head and neck cancer patients.

Cited by 27 publications

References 28 publications

Double-blind randomized study of oral glutamine on the management of radio/chemotherapy-induced mucositis and dermatitis in head and neck cancer

Double-blind randomized study of oral glutamine on the management of radio/chemotherapy-induced mucositis and dermatitis in head and neck cancer

β-Hydroxy-β-methylbutyrate Suppresses NF-ĸB Activation and IL-6 Production in TE-1 Cancer Cells

Gel de Chamomilla Recutita para reação de pele em paciente submetido à quimiorradioterapia: relato de caso

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