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. 2023 May 24;4:1191347. doi: 10.3389/froh.2023.1191347

Table 2.

Studies that employed topical chemoprevention agents to treat oral leukoplakia.

Reference/design study Chemopreventive protocol/sample (n) Outcomes/biomarkers Main results Side effects Follow-up
Wong et al., (39) CT Bleomycin 0.5% (n = 5)
Bleomycin 1% (n = 7)
1x day for 2 weeks
Clinical and histological CR: 1% - 3 cases complete
0.5% - 2 cases partial
HR: 0.5% - no improvement
1% - 3 cases complete
Burning, irritation, and erosion 23 months
Epstein et al., (40) RCT Bleomycin 1% (n = 10)
Placebo (n = 12)
1x day for 2 weeks
Clinical and histological CR: Bleomycin 50%
Placebo 8.3% (p = 0.001)
HR: Bleomycin 60%
Placebo 16.6% (p = 0.094)
Burning, pain, erythema with erosion 22 months
Piattelli et al., (41) CT Isotretinoin 0,1% gel (n = 6) Placebo (n = 3)
3x day for 4 months
Clinical
Protein biomarker: bcl-2 and Apoptotic analysis
CR: 10%
bcl-2 (p = 0.134)
Apoptotic bodies (p = 0.0193)
None 4 months
Tetê et al., (42) CT Isotretinoin 0,1% gel
Placebo (n = 15)
3x day for 4 months
Clinical
Protein biomarker: bcl-2 and Apoptotic analysis
CR: 3 cases
bcl-2 (p = 0.132)
Apoptotic bodies (p = 0.0193)
Not reported Not reported
Rudin et al., (13) CS Mouthwash ONYX-015 for p53-mutant cells
1 Cohort: 12 cycles (daily for 5 days) intervals 4 weeks (n = 7)
2 Cohort: 1x week for 24 weeks (n = 12)
3 Cohort: 5days + 1x week for 5 weeks (n = 3)
Histological
Protein biomarker: p53, Ki67 and cyclin D1
HR: 37%
p53 (p = 0.027).
Stomatitis, diarrhea, fatigue, pain, fever, flu symptoms, dysphagia, vertigo, and infection 30 months
Mulshine et al., (44) RCT Ketorolac rinse solution 0.1% 10 ml (n = 38)
Placebo (n = 19)
2x day for 33 days
Clinical and histological CR: Ketorolac 10.8%
Placebo 5.2% (p = 0.88)
HR: Ketorolac (p = 0.76)
Placebo (p = 0.80)
Pain (n = 1) 3 months
Scardina et al., (43) CT Isotretinoin 0,18% gel (n = 40)
2x day for 3 months
Clinical CR: 85% Transient erythema and xerostomia 120 months
Mallery et al., (45) RCT Dried black raspberries (DBR) 10% gel (n = 21)
Placebo (n = 19)
for 3 months
Clinical, histological
Molecular biomarkers: LOH
CR: DBR 76% (p = 0.0019)
Placebo 10% (p = 0.0395)
HR: DBR 40.9% (p = 0.0488)
Placebo 38.9% (p = 0.4961)
LOH: DBR 45.5% (p = 0.002)
Placebo 38.9% (p = 0.1602)
None 3 months

CS, case series; CT, clinical trial; RCT, randomized clinical trial; CT, clinical trial; CR, clinical response; HR, histological response; LOH, loss of heterozygosity.