Systemic Anti-Inflammatory Agents in the Prevention of Chemoradiation-Induced Mucositis: A Review of Randomised Controlled Trials
Abstract
:1. Introduction
1.1. Side Effects of Chemotherapy and Radiotherapy
1.2. Mucositis
1.2.1. Role of Inflammation in the Pathogenesis of Mucositis
1.2.2. Mechanism-Based Interventions for Mucositis
2. Overview of Available Preventative Strategies Using Systemic Anti-Inflammatories for Mucositis
3. Silymarin
4. Glutamine
5. Propolis
6. Cyclooxygenase-2 (COX-2) Inhibitors (Celecoxib)
7. Gabapentin
8. Zinc Sulphate
9. Corticosteroids (Prednisone)
10. Curcumin
11. Melatonin
12. Thalidomide
13. Calcitriol
14. Limitations of Current Evidence
15. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Author, Year | Study Type (Time) | Population | Intervention | Comparator | Outcomes | Summary of Main Effect Observed |
---|---|---|---|---|---|---|
Liang et al., 2022 [34] | Multicentre RCT (5 months) | Adults (N = 155) with nasopharyngeal carcinoma undergoing CRT | Thalidomide (75 mg) + basic oral hygiene guidance (N = 76) | Basic oral hygiene guidance (N = 79) | OM severity (WHO); mouth and throat soreness; body weight; adverse events | Intervention group had a significantly longer latency period and lower incidence of OM compared to control |
Elyasi et al., 2016 [35] | Prospective double-blind RCT (6 weeks) | Adults (N = 29) with HNC undergoing CRT | Conventional silymarin tablets (140 mg) (N = 13) | Placebo tablets (N = 14) | OM severity (WHO and CTCAE v.3) | Significantly lower OM severity and intolerable mucositis (stage 3–4) in the intervention group compared to control |
Hosseini et al., 2021 [36] | Double-blind RCT (6 weeks) | Adult SCC patients (N = 31) undergoing CRT | Nano-silymarin solution (70 mg/5 mL) (N = 16) | Placebo solution (5 mL) (N = 15) | OM severity (RTOG) | The intervention group had a non-significant decreasing OM severity trend compared to controls |
Bolouri et al., 2015 [37] | Triple-blind RCT (5 weeks) | HNC patients >15 years old undergoing RT (N = 20) | Propolis mouthwash (3%, 15 mL, swish and swallow) (N = 10) | Placebo mouthwash (15 mL, swish and swallow) (N = 10) | OM severity (NCI-CTC v.2); body weight | OM severity and mean weight loss in intervention group was significantly lower than in controls |
Salehi et al., 2018 [38] | Double- blind RCT (3 weeks) | Adults (N = 50) with colon cancer undergoing CT | Propolis (50 mg) capsule (N = 25) | Placebo capsule (N = 25) | OM severity (WHO) | There was a significant decrease in OM severity with intervention compared to control at day 14 and 21 |
Ertekin et al., 2004 [39] | Prospective double-blind RCT (13 weeks) | Adults (N = 27) with HNC undergoing RT only, or RT with concurrent CT | Zinc sulphate (50 mg zinc) capsule (N = 15) | Placebo capsule (N = 12) | OM severity (RTOG); body weight | OM onset was delayed in the intervention group and occurred at a lower severity and at an increased RT dose compared to controls |
Smith et al., 2020 [40] | Prospective RCT, no blinding (9 months) | Adults (N = 71) with HNC undergoing CRT | Standard therapy * + gabapentin capsule (N = 39) | Standard therapy. * (N = 32) | OM pain score (VHNSSv2); General Symptom Survey | OM pain and other symptoms were significantly reduced in the intervention group compared to controls |
Onseng et al., 2017 [41] | Double-blind RCT (7 weeks) | Adults (N = 39) with HNC undergoing CRT | Melatonin solution (10 mL, 0.2%) + melatonin capsule (20 mg) (N = 19) | Placebo solution (10 mL) + Placebo capsule (N = 20) | OM severity (WHO); xerostomia (CTCAE v4.03); Quality of Life scores (FACT-H&N); OM pain score (VAS) | Grade 3 OM onset was delayed by a median of 16 days and median morphine consumption for pain control was significantly lower in the intervention group compared to control |
Delavarian et al., 2019 [42] | Double-blind RCT (6 weeks) | Adults (N = 29) with HNC undergoing RT | Nano-curcumin (80 mg) soft gel (N = 15) | Placebo capsule (N = 14) | OM severity (NCI-CTC v.2); body weight | Delay in onset and reduced severity of OM, and reduced body weight loss were observed in the intervention group |
Kia et al., 2021 [43] | Double-blind RCT (7 weeks) | Cancer patients (N = 50) undergoing CT only, or CRT | Nano-curcumin (80 mg) soft gel (N = 25) | Placebo capsule (N = 25) | OM severity (WHO); OM pain score (NRS) | OM severity was significantly lower both for patients undergoing CT (all weeks) and for those undergoing CRT (weeks 4 and 7), with mean pain score significantly lower, in the intervention group compared to controls |
Alshawa et al., 2021 [44] | Double-blind RCT (9 months) | Adults (N = 38) with thoracic malignancies undergoing RT or CRT | Glutamine suspension (N = 19) | Placebo (glycine) suspension (N = 19) | Esophagitis severity (CTCAE v4.03); body weight; symptom burden (MDASI-HN); Study Medication Satisfaction Scale | No significant differences observed for outcome except core symptom severity, which was higher in the intervention group |
Lalla et al., 2014 [45] | Prospective multicentre, double-blind RCT (8 weeks) | Adults (N = 40) with HNC undergoing RT | Celecoxib (200 mg) capsule (N = 19) | Placebo capsule (N = 20) | OM severity (OMAS, WHO, CNI-CTCv.2); pain score (Brief Pain Inventory); analgesic use; diet (Performance Status Scale) | No mean OM severity (on all scales used), pain scores, normalcy of diet, nor opioid analgesic use had a significant difference between groups |
Leborgne et al., 1998 [46] | Double-blind RCT (13 weeks) | SCC patients (N = 66) undergoing RT | Prednisone capsules (20–40 mg) (N = 32) | Placebo capsule (N = 34) | Total duration of treatment and interruptions; OM severity (WHO); hospitalisation and nutritional support; body weight | Significant decrease in RT treatment time for the intervention group; body weight loss average was less severe in the intervention group |
Hamidieh et al., 2016 [47] | Double-blind RCT (5 weeks) | Children (N = 28) with Fanconi anaemia receiving high-dose CT conditioning regimen prior to undergoing allogeneic HSCT. | OM prophylaxis regimen ** + Calcitriol (0.025 μg) capsule (N = 14) | OM prophylaxis regimen * + Placebo capsule (N = 14) | OM severity (WHO); baseline serum 25-OH vitamin D level | Baseline sufficient (>20 ng/mL) vitamin D level was significantly associated with complete OM resolution to grades 0–1; recovery of grades 3–4 OM to lower grades was significantly associated with non-deficient vitamin D levels. |
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Mohammed, A.I.; Fedoruk, L.; Fisher, N.; Liu, A.X.; Khanna, S.; Naylor, K.; Gong, Z.; Celentano, A.; Alrashdan, M.S.; Cirillo, N. Systemic Anti-Inflammatory Agents in the Prevention of Chemoradiation-Induced Mucositis: A Review of Randomised Controlled Trials. Biomolecules 2024, 14, 560. https://doi.org/10.3390/biom14050560
Mohammed AI, Fedoruk L, Fisher N, Liu AX, Khanna S, Naylor K, Gong Z, Celentano A, Alrashdan MS, Cirillo N. Systemic Anti-Inflammatory Agents in the Prevention of Chemoradiation-Induced Mucositis: A Review of Randomised Controlled Trials. Biomolecules. 2024; 14(5):560. https://doi.org/10.3390/biom14050560
Chicago/Turabian StyleMohammed, Ali I., Lexi Fedoruk, Nicholas Fisher, Andy Xiaoqian Liu, Samar Khanna, Kaelan Naylor, Ziyi Gong, Antonio Celentano, Mohammad S. Alrashdan, and Nicola Cirillo. 2024. "Systemic Anti-Inflammatory Agents in the Prevention of Chemoradiation-Induced Mucositis: A Review of Randomised Controlled Trials" Biomolecules 14, no. 5: 560. https://doi.org/10.3390/biom14050560