Double‐blind placebo‐controlled randomized clinical trial evaluating doxycycline effects on chemotherapy‐induced oral mucositis

Ramírez‐Amador, Velia; Anaya‐Saavedra, Gabriela; Labardini-Méndez, J; León-Rosales, Sergio Ponce de

doi:10.1111/jcpt.12633

Cited by 4 publications

(5 citation statements)

References 39 publications

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“…AZD3342 did not protect against MTX-induced intestinal barrier dysfunction, weight loss, or histopathological injury. These findings are consistent with previous research showing MMP inhibition with doxycycline was unable to attenuate chemotherapy-induced oral mucositis [21]. They are, however, inconsistent with a growing body of evidence implicating MMPs in intestinal inflammation and demonstrated efficacy of MMP inhibition.…”

Section: Discussionsupporting

confidence: 76%

Selective MMP Inhibition, Using AZD3342, to Reduce Gastrointestinal Toxicity and Enhance Chemoefficacy in a Rat Model

et al. 2018

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Background: The common cytotoxic mechanisms that underpin chemoefficacy and toxicity have hampered efforts to deliver effective supportive care interventions, particularly for gastrointestinal (GI) toxicity. Matrix metalloproteinases (MMPs) have been implicated in both tumor growth and GI toxicity, and as such MMP inhibitors present as a novel therapeutic avenue to simultaneously enhance treatment efficacy and reduce toxicity. Objectives: The aim of this study was to determine the efficacy of an MMP-9/12 inhibitor, AZD3342, on tumor growth and GI toxicity in a rat model. Methods: Female tumor-bearing Dark Agouti rats (n = 90) were divided into 4 groups: vehicle control; methotrexate (MTX); AZD3342, and MTX + AZD3342. Tumors were measured daily (for 5 days) using digital calipers. GI toxicity was assessed using well-established clinical markers (diarrhea/weight loss), histopathological analysis, and functional assessment of intestinal barrier permeability. Results: AZD3342 delayed the onset of severe diarrhea by 1 day (vs. MTX) but was unable to improve the overall severity of diarrhea. No changes were detected in tissue morphology or intestinal barrier function. AZD3342 alone suppressed tumor growth (p = 0.003 vs. vehicle) but did not enhance the efficacy of MTX. Conclusions: This study showed partial efficacy of AZD3342 in reducing tumor growth and delaying the onset of severe diarrhea caused by MTX in rats. We suggest further studies be undertaken targeting appropriate scheduling of AZD3342 as well as investigating different cytotoxic therapies that strongly activate MMP signaling.

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Section: Discussionsupporting

confidence: 76%

Selective MMP Inhibition, Using AZD3342, to Reduce Gastrointestinal Toxicity and Enhance Chemoefficacy in a Rat Model

et al. 2018

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“…Studies show that in addition to the antimicrobial effect, doxycycline has a potent anti‐inflammatory effect. In view of these pharmacological characteristics, some authors have suggested the use of topical and/or systemic doxycycline for the treatment of inflammatory, autoimmune and granulomatous diseases . Based on these properties, the present study aimed to review the literature investigating doxycycline as a therapeutic option in the management of ulcerated oral lesions.…”

Section: Discussionmentioning

confidence: 99%

Doxycycline: An option in the treatment of ulcerated oral lesions?

et al. 2019

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What is known and objectives In addition to its antimicrobial effect, doxycycline has potent anti‐inflammatory activity. In view of these pharmacological characteristics, its use in the management of inflammatory, autoimmune and granulomatous diseases has been proposed. The objective of this study was to investigate, through a systematic literature review, the effect of doxycycline on pain and healing of ulcerated lesions of the mouth. Methods An electronic search was performed in accordance with PRISMA guidelines in PubMed, Cochrane Central Register, Web of Science, Bireme/LILACS and Scopus databases. Controlled, randomized clinical trials were selected. The concentration of doxycycline, frequency of application, pain relief and clinical remission of the lesions were analysed. Results and discussion According to the inclusion criteria, five articles were selected. In four of these studies, doxycycline was used in the treatment of aphthous stomatitis, and in one study, it was used in the treatment of herpes labialis. In all studies, the drug was used topically, both as a hydrogel and as a crushed tablet (along with a prosthetic adhesive). The groups treated with doxycycline showed faster healing of lesions and lower pain scores compared to placebo. What is new and conclusion The present study suggests that topical doxycycline has a positive effect on the treatment of recurrent aphthous ulceration and herpes labialis. Experimental animal studies and double‐blind randomized clinical trials should be performed on other oral lesions, such as traumatic ulcers and mucositis.

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“…36 A randomized clinical trial done to evaluate the effect of sub antimicrobial dose of doxycycline on chemotherapy-induced oral mucositis proved to be ineffective. 37 More research is needed to ascertain the efficacy of sub antimicrobial dose of doxycycline in treating oral mucositis. Developing comprehensive treatment plans to control the infection and inflammation in the oral cavity is essential.…”

Section: Discussionmentioning

confidence: 99%

Oral Mucositis: Role of the Dentist

Madeswaran¹,

Saravanan²,

Rethinam³

et al. 2019

Journal of Oral Health and Community Dentistry

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Oral mucositis is the inflammation of the oral mucosa that occurs as a side effect of cytotoxic cancer therapy. Though the condition cannot be prevented, steps can be taken to decrease the severity and for the desired therapeutic outcome of cancer therapy. The communication between the oncologist and dentist becomes vital for the patient benefit. A search of the resources through Medline and Google Scholar was made to comprehend the pathobiology, clinical characteristics, and various therapeutic methods related to oral mucositis. A total of 63 articles were chosen for reference, which mostly includes recent year review papers. After the final screening, 29 research papers were selected for the current study. Controlling the predisposing risk factors pertaining to the oral cavity and recording the baseline oral health status before the commencement of cancer therapy is crucial. Patients are counseled for proper oral hygiene routine, and lifelong follow-up.

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Double‐blind placebo‐controlled randomized clinical trial evaluating doxycycline effects on chemotherapy‐induced oral mucositis

Abstract: Subantimicrobial doses of doxycycline did not reduce the incidence, onset, duration or severity of OM.

Cited by 4 publications

References 39 publications

Selective MMP Inhibition, Using AZD3342, to Reduce Gastrointestinal Toxicity and Enhance Chemoefficacy in a Rat Model

Selective MMP Inhibition, Using AZD3342, to Reduce Gastrointestinal Toxicity and Enhance Chemoefficacy in a Rat Model

Doxycycline: An option in the treatment of ulcerated oral lesions?

Oral Mucositis: Role of the Dentist

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