Abstract

Head and neck cancer (HNC) is a complex and heterogeneous disease associated with high mortality and morbidity worldwide. Standard therapeutic management of advanced HNC, which is based on radiotherapy often combined with chemotherapy, has been hampered by severe long-term side effects. To overcome these side effects, tumor-selective nanoparticles have been exploited as a potential drug delivery system to improve HNC therapy. A combination of MEDLINE, EMBASE, Cochrane Oral Health Group’s Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov from inception up to June 2020 was used for this systematic review. A total of 1747 published manuscripts were reviewed and nine relevant references were retrieved for analysis, while eight of them were eligible for meta-analysis. Based on these studies, the level of evidence about the efficacy of nanoformulation for HNC therapy on tumor response and adverse side effects (SAE) was low. Even though basic research studies have revealed a greater promise of nanomaterial to improve the outcome of cancer therapy, none of them were translated into clinical benefits for HNC patients. This systematic review summarized and discussed the recent progress in the development of targeted nanoparticle approaches for HNC management, and open-up new avenues for future perspectives.

Highlights

  • Head and neck cancer (HNC) is a complex multifactorial disease that originates in the epithelial layer of mucosa of the upper aerodigestive tract, including the oral cavity, pharynx and larynx showing microscopic evidence of squamous differentiation [1,2]

  • Second outcomes were the Severe Adverse Effects (SAE) classified as grade III and IV according to Common Toxicity Criteria (CTC) v2.0 [14]

  • Of the nine manuscripts exploring nanoparticles in HNC, four of them were classified at Phase I (44.4%) and five at Phase II (55.6%) non-randomized controlled clinical trials

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Summary

Introduction

Head and neck cancer (HNC) is a complex multifactorial disease that originates in the epithelial layer of mucosa of the upper aerodigestive tract, including the oral cavity, pharynx and larynx showing microscopic evidence of squamous differentiation [1,2]. It is estimated that 60% of the patients are diagnosed with advanced disease (stage III and IV) leading to low survival rates In these cases, the treatment consists of surgical ablation followed by adjuvant radiation or chemoradiation (CRT) [3,4]. The United States Food and Drug Administration (FDA) categorized nanomaterials based on the delivery vehicle or carrier as liposomal, polymeric, albumin-bounds, polymer-bounds, and inorganic particles [8]. These materials have been explored to overcome the biological barriers to cancer treatment due to their unique features such as a large surface area allowing conjugation to biologically active molecules, structural properties (optical, electronic, catalytic and magnetic) and a long time circulation in blood compared with small molecules. We summarized and discussed the recent progress in the development of targeted nanoparticles systems for HNC therapy opening new avenues for future opportunities of investigations in the field

Materials and Methods
Literature Search
Study Selection
Data Extraction and Study Quality Assessment
Risk of Bias Assessment
Types of Outcome Measures
Statistical Analysis
Study Overview
Interventions in HNC Using Chemotherapy Nanoformulations
Tumor Response and Host Toxicity
Platinum-Based Chemotherapy
Doxorubicin
Paclitaxel
Ongoing Clinical Trials
Outcomes
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