Table 1.

Prevention Randomized Placebo Controlled Clinical Trials in HNSCC

Study Year	Number of participants	Intervention/control	Main Results
Hong ⁶⁵ 1986	44	13-cis-retinoic acid (13-cRA) Placebo	Response rates among patients with dysplasia: 54% (13- cRA) versus 10% (placebo)
^* Hong ⁶⁶ 1990	103	13-cis-retinoic acid (13-cRA) placebo	Decreased 2 ^nd primary tumors (4% vs. 24%)
Sankaranarayanan ⁶⁷ 1997	160	Vitamin A BC Placebo	Complete regression: Vitamin A 52%, BC 33%, placebo 10%
^* van Zandwijk ⁶⁸ 2000	2592	retinyl palmitate RP) N-acetyl cysteine (NAC) RP + NAC placebo	No effect on second primary tumors
^* Mayne ⁶⁹ 2001	264	BC Placebo	BC does not have pro-oxidant effects
^* Bairati ⁷⁰ 2005	540	Alpha-tocopherol + BC (terminated after 156 participants randomized) Placebo	No effect overall; increased second primary tumors in first 3.5 yrs., decreased second primary tumors afterwards
^* Khuri ²⁹ 2006	1190	Isotretinoin Placebo	No effect on second primary tumors
Papadimitrakopoulou ⁷¹ 2008	50	Celecoxib Placebo	No significant effect

endpoint was second primary tumors

OPL, oral premalignant lesions, BC, Beta carotene, RP, retinyl palmitate, NAC, N-acetyl cysteine