A Randomized Double-Blind Placebo-Controlled Phase IIB Trial of Curcumin in Oral Leukoplakia.
Oral leukoplakia is a potentially malignant lesion of the oral cavity, for which no effective treatment is available. We investigated the effectiveness of curcumin, a potent inhibitor of NF-κB/COX-2, molecules perturbed in oral carcinogenesis, to treat leukoplakia. Subjects with oral leukoplakia (n = 223) were randomized (1:1 ratio) to receive orally, either 3.6 g/day of curcumin (n = 111) or placebo (n = 112), for 6 months. The primary endpoint was clinical response obtained by bi-dimensional measurement of leukoplakia size at recruitment and 6 months. Histologic response, combined clinical and histologic response, durability and effect of long-term therapy for an additional six months in partial responders, safety and compliance were the secondary endpoints. Clinical response was observed in 75 (67.5%) subjects [95% confidence interval (CI), 58.4-75.6] in the curcumin and 62 (55.3%; 95% CI, 46.1-64.2) in placebo arm (P = 0.03). This response was durable, with 16 of the 18 (88.9%; 95% CI, 67.2-96.9) subjects with complete response in curcumin and 7 of 8 subjects (87.5%) in placebo arm, demonstrating no relapse after 6 months follow-up. Difference in histologic response between curcumin and placebo was not significant (HR, 0.88, 95% CI, 0.45-1.71; P = 0.71). Combined clinical and histologic response assessment indicated a significantly better response with curcumin (HR, 0.50; 95% CI, 0.27-0.92; P = 0.02). Continued therapy, in subjects with partial response at 6 months, did not yield additional benefit. The treatment did not raise any safety concerns. Treatment of oral leukoplakia with curcumin (3.6 g for six months), thus was well tolerated and demonstrated significant and durable clinical response for 6 months. Cancer Prev Res; 9(8); 683-91. ©2016 AACR.
Amrita Institute of Medical Sciences, Kochi, India. Mazumdar Shaw Cancer Center, Bengaluru, India. Roswell Park Cancer Institute, Buffalo, New York. makuriakose@gmail.com mrpillai@rgcb.res.in.
Moni Abraham
MA
Kuriakose
Regional Cancer Center, Thiruvananthapuram, India.
Kunnambath
K
Ramdas
Department of Biotechnology, Ministry of Science and Technology, New Delhi, India.
Bindu
B
Dey
Amrita Institute of Medical Sciences, Kochi, India.
Subramanya
S
Iyer
Chennai Dental Research Foundation, Chennai, India.
Gunaseelan
G
Rajan
Amrita Institute of Medical Sciences, Kochi, India.
Kalavathy K
KK
Elango
Amrita Institute of Medical Sciences, Kochi, India. Mazumdar Shaw Cancer Center, Bengaluru, India. Roswell Park Cancer Institute, Buffalo, New York.
Amritha
A
Suresh
Regional Cancer Center, Thiruvananthapuram, India.
Divya
D
Ravindran
Regional Cancer Center, Thiruvananthapuram, India.
Rajneesh R
RR
Kumar
Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, India.
Prathiba
P
R
Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, India.
Surya
S
Ramachandran
Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, India.
Nisha Asok
NA
Kumar
Regional Cancer Center, Thiruvananthapuram, India.
Gigi
G
Thomas
Regional Cancer Center, Thiruvananthapuram, India.
Thara
T
Somanathan
Amrita Institute of Medical Sciences, Kochi, India.
Hiran K
HK
Ravindran
Chennai Dental Research Foundation, Chennai, India.
Kannan
K
Ranganathan
Manipal Acunova, Bengaluru, India.
Sudhakar Babu
SB
Katakam
Manipal Acunova, Bengaluru, India.
Shivashankar
S
Parashuram
Roswell Park Cancer Institute, Buffalo, New York.
Vijayvel
V
Jayaprakash
Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, India. makuriakose@gmail.com mrpillai@rgcb.res.in.
M Radhakrishna
MR
Pillai
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001706:Biopsy; D001772:Blood Cell Count; D003474:Curcumin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007972:Leukoplakia, Oral / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010919:Placebos; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D016328:NF-kappa B; D010919:Placebos; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D003474:Curcumin