Non-Cochrane · intervention · PM42445442
Effects of different drugs on radiation-induced oral mucositis in patients with head and neck tumors: a systematic review and a network meta-analysis.
Lou Shuchang, Li Xiaodong, Shi Lingyun · Translational cancer research · 2026 · PubMed · doi:10.21037/tcr-2026-0538
Findings
Population Adults with head and neck cancer receiving radiotherapy or chemoradiotherapy
51 findings
| cytokine | amifostine | Duration of RIOM (days) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | MD 13.62 [-13.58, 40.81] GRADE not reported 9 studies · 825 participants |
| cytokine | amifostine | Number of reported >= grade II xerostomia cases End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 1.27 [0.35, 4.57] GRADE not reported 6 studies · 966 participants |
| cytokine | amifostine | Number of patients with a feeding tube End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 5.46 [0.22, 136.77] GRADE not reported 12 studies · 1020 participants |
| cytokine | amifostine | Number of reported cases of severe (>= grade III) RIOM End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 0.43 [0.15, 1.25] GRADE not reported 24 studies |
| cytokine | amifostine | Number of reported dysphagia cases (>= grade III dysphagia) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 10.28 [1.09, 96.79] GRADE not reported 6 studies · 479 participants |
| cytokine | amifostine | Number of treatment interruption cases End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 13.01 [1.24, 136.69] GRADE not reported 7 studies · 542 participants |
| glutamine | amifostine | Number of patients with a feeding tube End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 1.10 [0.04, 30.11] GRADE not reported 12 studies · 1020 participants |
| glutamine | amifostine | Number of reported cases of severe (>= grade III) RIOM End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 0.13 [0.03, 0.51] GRADE not reported 24 studies |
| glutamine | amifostine | Number of treatment interruption cases End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 0.42 [0.03, 5.86] GRADE not reported 7 studies · 542 participants |
| glutamine | amifostine | Number of reported dysphagia cases (>= grade III dysphagia) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 11.09 [1.10, 112.24] GRADE not reported 6 studies · 479 participants |
| glutamine | amifostine | Duration of RIOM (days) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | MD 17.70 [-8.43, 43.83] GRADE not reported 9 studies · 825 participants |
| calcium phosphate | amifostine | Number of reported cases of severe (>= grade III) RIOM End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 0.73 [0.16, 3.42] GRADE not reported 24 studies |
| calcium phosphate | amifostine | Number of reported dysphagia cases (>= grade III dysphagia) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 1.12 [0.09, 14.08] GRADE not reported 6 studies · 479 participants |
| calcium phosphate | amifostine | Duration of RIOM (days) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | MD 22.14 [-7.74, 52.01] GRADE not reported 9 studies · 825 participants |
| placebo or no-treatment control | amifostine | Number of reported dysphagia cases (>= grade III dysphagia) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 12.54 [1.41, 111.20] GRADE not reported 6 studies · 479 participants |
| placebo or no-treatment control | amifostine | Number of patients with a feeding tube End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 5.83 [0.24, 140.53] GRADE not reported 12 studies · 1020 participants |
| placebo or no-treatment control | amifostine | Number of reported cases of severe (>= grade III) RIOM End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 1.02 [0.41, 2.54] GRADE not reported 24 studies |
| placebo or no-treatment control | amifostine | Number of treatment interruption cases End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 22.75 [2.98, 173.84] GRADE not reported 7 studies · 542 participants |
| placebo or no-treatment control | amifostine | Number of reported >= grade II xerostomia cases End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 1.52 [0.62, 3.75] GRADE not reported 6 studies · 966 participants |
| placebo or no-treatment control | amifostine | Duration of RIOM (days) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | MD 22.84 [-2.06, 47.73] GRADE not reported 9 studies · 825 participants |
| glutamine | cytokine | Duration of RIOM (days) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | MD 4.08 [-9.50, 17.66] GRADE not reported 9 studies · 825 participants |
| glutamine | cytokine | Number of reported cases of severe (>= grade III) RIOM End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 0.31 [0.10, 0.99] GRADE not reported 24 studies |
| glutamine | cytokine | Number of patients with a feeding tube End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 0.20 [0.07, 0.55] GRADE not reported 12 studies · 1020 participants |
| glutamine | cytokine | Number of patients using analgesics End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 0.56 [0.02, 15.48] GRADE not reported 7 studies · 485 participants |
| glutamine | cytokine | Number of treatment interruption cases End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 0.03 [0.00, 0.31] GRADE not reported 7 studies · 542 participants |
| calcium phosphate | cytokine | Duration of RIOM (days) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | MD 8.52 [-11.31, 28.34] GRADE not reported 9 studies · 825 participants |
| calcium phosphate | cytokine | Number of reported cases of severe (>= grade III) RIOM End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 1.73 [0.44, 6.80] GRADE not reported 24 studies |
| placebo or no-treatment control | cytokine | Duration of RIOM (days) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | MD 9.22 [-1.73, 20.17] GRADE not reported 9 studies · 825 participants |
| placebo or no-treatment control | cytokine | Number of patients using analgesics End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 1.99 [0.17, 23.94] GRADE not reported 7 studies · 485 participants |
| placebo or no-treatment control | cytokine | Number of patients with a feeding tube End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 1.07 [0.65, 1.77] GRADE not reported 12 studies · 1020 participants |
| placebo or no-treatment control | cytokine | Number of reported >= grade II xerostomia cases End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 1.20 [0.48, 2.95] GRADE not reported 6 studies · 966 participants |
| placebo or no-treatment control | cytokine | Number of treatment interruption cases End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 1.75 [0.54, 5.68] GRADE not reported 7 studies · 542 participants |
| placebo or no-treatment control | cytokine | Number of reported dysphagia cases (>= grade III dysphagia) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 1.22 [0.73, 2.04] GRADE not reported 6 studies · 479 participants |
| placebo or no-treatment control | cytokine | Number of reported cases of severe (>= grade III) RIOM End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 2.40 [1.33, 4.32] GRADE not reported 24 studies |
| calcium phosphate | glutamine | Duration of RIOM (days) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | MD 4.44 [-13.95, 22.82] GRADE not reported 9 studies · 825 participants |
| calcium phosphate | glutamine | Weight loss (kg) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | MD 0.72 [-3.06, 4.51] GRADE not reported 4 studies · 310 participants |
| calcium phosphate | glutamine | Number of reported cases of severe (>= grade III) RIOM End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 5.52 [1.13, 27.07] GRADE not reported 24 studies |
| calcium phosphate | glutamine | Number of reported dysphagia cases (>= grade III dysphagia) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 0.10 [0.02, 0.45] GRADE not reported 6 studies · 479 participants |
| placebo or no-treatment control | glutamine | Number of patients with a feeding tube End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 5.30 [2.13, 13.16] GRADE not reported 12 studies · 1020 participants |
| placebo or no-treatment control | glutamine | Number of treatment interruption cases End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 54.45 [10.07, 294.42] GRADE not reported 7 studies · 542 participants |
| placebo or no-treatment control | glutamine | Number of reported cases of severe (>= grade III) RIOM End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 7.67 [2.84, 20.72] GRADE not reported 24 studies |
| placebo or no-treatment control | glutamine | Number of reported dysphagia cases (>= grade III dysphagia) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 1.13 [0.52, 2.44] GRADE not reported 6 studies · 479 participants |
| placebo or no-treatment control | glutamine | Weight loss (kg) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | MD 0.62 [-1.60, 2.85] GRADE not reported 4 studies · 310 participants |
| placebo or no-treatment control | glutamine | Number of patients using analgesics End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 3.55 [0.40, 31.53] GRADE not reported 7 studies · 485 participants |
| placebo or no-treatment control | glutamine | Duration of RIOM (days) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | MD 5.14 [-2.92, 13.19] GRADE not reported 9 studies · 825 participants |
| placebo or no-treatment control | calcium phosphate | Number of reported dysphagia cases (>= grade III dysphagia) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 11.23 [3.10, 40.72] GRADE not reported 6 studies · 479 participants |
| placebo or no-treatment control | calcium phosphate | Number of reported cases of severe (>= grade III) RIOM End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 1.39 [0.40, 4.80] GRADE not reported 24 studies |
| placebo or no-treatment control | calcium phosphate | Duration of RIOM (days) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | MD 0.70 [-15.83, 17.23] GRADE not reported 9 studies · 825 participants |
| placebo or no-treatment control | calcium phosphate | Weight loss (kg) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | MD -0.10 [-3.16, 2.96] GRADE not reported 4 studies · 310 participants |
| cytokine | glutamine | Number of reported dysphagia cases (>= grade III dysphagia) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 0.93 [0.37, 2.34] GRADE not reported 6 studies · 479 participants |
| cytokine | calcium phosphate | Number of reported dysphagia cases (>= grade III dysphagia) End of radiotherapy (week 7) or closest reported time point · Head and neck cancer radiotherapy or chemoradiotherapy | OR 9.20 [2.30, 36.86] GRADE not reported 6 studies · 479 participants |
Included primary studies 28
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Yang 2016 matched by author and year (probable) | NR | 1 other review | not stated | not extracted yet |
| Antonadou 2002 Prophylactic use of amifostine to prevent radiochemotherapy-induced mucositis and xerostomia in head-and-neck cancer. PMID:11849797 | 2002 | this review only | not stated | not extracted yet |
| Bourhis 2000 A randomized study of very accelerated radiotherapy with and without amifostine in head and neck squamous cell carcinoma. PMID:10725619 | 2000 | this review only | not stated | not extracted yet |
| Brizel 2000 Phase III randomized trial of amifostine as a radioprotector in head and neck cancer. PMID:11013273 | 2000 | this review only | not stated | not extracted yet |
| Brizel 2008 Phase II study of palifermin and concurrent chemoradiation in head and neck squamous cell carcinoma. PMID:18487568 | 2008 | this review only | not stated | not extracted yet |
| Buentzel 2005 Intravenous amifostine during chemoradiotherapy for head-and-neck cancer: a randomized placebo-controlled phase III study. PMID:16243440 | 2006 | this review only | not stated | not extracted yet |
| Cerchietti 2006 Double-blinded, placebo-controlled trial on intravenous L-alanyl-L-glutamine in the incidence of oral mucositis following… PMID:16765532 | 2006 | this review only | not stated | not extracted yet |
| Chattopadhyay 2014 Role of oral glutamine in alleviation and prevention of radiation-induced oral mucositis: A prospective randomized study. PMID:24665438 | 2014 | this review only | not stated | not extracted yet |
| Haddad 2009 Randomized phase 2 study of concomitant chemoradiotherapy using weekly carboplatin/paclitaxel with or without daily subcutaneous… PMID:19634161 | 2009 | this review only | not stated | not extracted yet |
| Henke 2011 Palifermin decreases severe oral mucositis of patients undergoing postoperative radiochemotherapy for head and neck cancer: a randomized,… PMID:21670447 | 2011 | this review only | not stated | not extracted yet |
| Hoffman 2014 The impact of concurrent granulocyte-macrophage colony-stimulating factor on quality of life in head and neck cancer patients: results of… PMID:24492945 | 2014 | this review only | not stated | not extracted yet |
| Huang 2000 Oral glutamine to alleviate radiation-induced oral mucositis: a pilot randomized trial. PMID:10701731 | 2000 | this review only | not stated | not extracted yet |
| Huang 2019 Randomized double-blind, placebo-controlled trial evaluating oral glutamine on radiation-induced oral mucositis and dermatitis in head and… PMID:30753262 | 2019 | this review only | not stated | not extracted yet |
| Khanum 2019 Penetration of cefonicid into serum, salpinges, cervix and vaginal tissue. PMID:2019859 | 1991 | this review only | not stated | not extracted yet |
| Lambrecht 2013 The effect of a supersaturated calcium phosphate mouth rinse on the development of oral mucositis in head and neck cancer patients treated… PMID:23686379 | 2013 | this review only | not stated | not extracted yet |
| Le 2011 Palifermin reduces severe mucositis in definitive chemoradiotherapy of locally advanced head and neck cancer: a randomized,… PMID:21670453 | 2011 | this review only | not stated | not extracted yet |
| Lopez-Vaquero 2017 Double-blind randomized study of oral glutamine on the management of radio/chemotherapy-induced mucositis and dermatitis in head and neck… PMID:28588793 | 2017 | this review only | not stated | not extracted yet |
| McAleese 2006 Randomized phase II study of GM-CSF to reduce mucositis caused by accelerated radiotherapy of laryngeal cancer. PMID:16823067 | 2006 | this review only | not stated | not extracted yet |
| Pan 2017 [Effect of recombinant human interleukin-11 treatment on prognosis of patients with radiochemoradiotherapy in the treatment of… PMID:29798418 | 2017 | this review only | not stated | not extracted yet |
| Pathak 2019 A Randomized Controlled Trial to Evaluate the Role and Efficacy of Oral Glutamine in the Treatment of Chemo-radiotherapy-induced Oral… PMID:31410338 | 2019 | this review only | not stated | not extracted yet |
| Pattanayak 2016 Management of Chemoradiation-Induced Mucositis in Head and Neck Cancers With Oral Glutamine. PMID:28717702 | 2016 | this review only | not stated | not extracted yet |
| Ryu 2007 The impact of concurrent granulocyte macrophage-colony stimulating factor on radiation-induced mucositis in head and neck cancer patients:… PMID:17293228 | 2007 | this review only | not stated | not extracted yet |
| Saarilahti 2002 Comparison of granulocyte-macrophage colony-stimulating factor and sucralfate mouthwashes in the prevention of radiation-induced… PMID:12243825 | 2002 | this review only | not stated | not extracted yet |
| Sarumathy 2012 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Shang 2014 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Su 2006 Double-blind, placebo-controlled, randomized trial of granulocyte-colony stimulating factor during postoperative radiotherapy for squamous… PMID:16803675 | 2006 | this review only | not stated | not extracted yet |
| Tsujimoto 2015 L-glutamine decreases the severity of mucositis induced by chemoradiotherapy in patients with locally advanced head and neck cancer: a… PMID:25351453 | 2015 | this review only | not stated | not extracted yet |
| Wong 2017 A randomised controlled trial of Caphosol mouthwash in management of radiation-induced mucositis in head and neck cancer. PMID:27393218 | 2017 | this review only | not stated | not extracted yet |
Overlap with other reviews
Reviews that include the same primary studies are not independent evidence. Shared counts match studies by PMID, DOI or NCT, and otherwise by author and year (a probable match). Only the non-Cochrane dental reviews have study lists, so overlap with Cochrane reviews is not counted yet.
| Review | Shared studies | Jaccard |
|---|---|---|
| Assessment of genetic susceptibility in patients with oral squamous cell carcinoma: a systematic review and meta-analysis. (2026) | 1 | 0.00 |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Adults (18 years or older) with pathologically confirmed head and neck tumors who developed radiation-induced oral mucositis (WHO, RTOG or CTCAE criteria) and received definitive radiotherapy, adjuvant radiotherapy or concurrent chemoradiotherapy | Patients with head and neck cancer, mostly stage III to IV, mean age 47 to 67 years, about 75% male (29 RCTs, n=2,276) |
| Intervention | Amifostine, cytokine, glutamine or calcium phosphate | Amifostine (5 RCTs), cytokines (12 RCTs), glutamine (10 RCTs), calcium phosphate (2 RCTs) |
| Comparison | Blank (no treatment) or placebo control | Placebo, no treatment (blank) or standard care; no head-to-head trials between the drugs |
| Outcomes | Primary: severity of RIOM, duration of RIOM, severity of xerostomia, severity of dysphagia. Secondary: use of analgesics, weight loss, use of feeding tube, treatment interruption | RIOM cases (24 RCTs), RIOM duration (9 RCTs, n=825), grade II or higher xerostomia (6 RCTs, n=966), dysphagia (6 RCTs, n=479), analgesic use (7 RCTs, n=485), weight loss (4 RCTs, n=310), feeding tube (12 RCTs, n=1,020), treatment interruption (7 RCTs, n=542) |
| Study designs | RCTs, English language only | 29 RCTs published 2000 to 2025 |
| Timing | Outcomes recorded as close to the end of radiotherapy (week 7) as possible | Follow-up 5 weeks to 34 months; network outcomes at end of radiotherapy |
AMSTAR 2 items
Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | Partial Yes | Partial Yes | yes |
| 3Choice of study designs explained | No | No | yes |
| 4Comprehensive literature searchcritical | No | No | yes |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | No | No | yes |
| 8Included studies described in detail | Partial Yes | Partial Yes | yes |
| 9Risk of bias assessed satisfactorilycritical | RCT: Yes | RCT: Yes | yes |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | RCT: No | RCT: Yes | no |
| 12Impact of risk of bias on the pooled results | No | No | yes |
| 13Risk of bias accounted for in interpretationcritical | No | No | yes |
| 14Heterogeneity explained | No | No | yes |
| 15Publication bias investigatedcritical | Yes | Yes | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Critically Low | Critically Low | yes |