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...
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| Published in: | Cancer prevention research (Philadelphia, Pa.) Vol. 9; no. 8; pp. 683 - 691 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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United States
01.08.2016
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| ISSN: | 1940-6215 |
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| Abstract | 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. |
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| AbstractList | 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. |
| Author | Kumar, Nisha Asok Ramachandran, Surya Ranganathan, Kannan Kuriakose, Moni Abraham Elango, Kalavathy K Ravindran, Hiran K Somanathan, Thara Jayaprakash, Vijayvel Iyer, Subramanya Parashuram, Shivashankar Ramdas, Kunnambath Pillai, M Radhakrishna R, Prathiba Kumar, Rajneesh R Thomas, Gigi Katakam, Sudhakar Babu Suresh, Amritha Dey, Bindu Ravindran, Divya Rajan, Gunaseelan |
| Author_xml | – sequence: 1 givenname: Moni Abraham surname: Kuriakose fullname: Kuriakose, Moni Abraham email: makuriakose@gmail.com, mrpillai@rgcb.res.in organization: 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 – sequence: 2 givenname: Kunnambath surname: Ramdas fullname: Ramdas, Kunnambath organization: Regional Cancer Center, Thiruvananthapuram, India – sequence: 3 givenname: Bindu surname: Dey fullname: Dey, Bindu organization: Department of Biotechnology, Ministry of Science and Technology, New Delhi, India – sequence: 4 givenname: Subramanya surname: Iyer fullname: Iyer, Subramanya organization: Amrita Institute of Medical Sciences, Kochi, India – sequence: 5 givenname: Gunaseelan surname: Rajan fullname: Rajan, Gunaseelan organization: Chennai Dental Research Foundation, Chennai, India – sequence: 6 givenname: Kalavathy K surname: Elango fullname: Elango, Kalavathy K organization: Amrita Institute of Medical Sciences, Kochi, India – sequence: 7 givenname: Amritha surname: Suresh fullname: Suresh, Amritha organization: Amrita Institute of Medical Sciences, Kochi, India. Mazumdar Shaw Cancer Center, Bengaluru, India. Roswell Park Cancer Institute, Buffalo, New York – sequence: 8 givenname: Divya surname: Ravindran fullname: Ravindran, Divya organization: Regional Cancer Center, Thiruvananthapuram, India – sequence: 9 givenname: Rajneesh R surname: Kumar fullname: Kumar, Rajneesh R organization: Regional Cancer Center, Thiruvananthapuram, India – sequence: 10 givenname: Prathiba surname: R fullname: R, Prathiba organization: Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, India – sequence: 11 givenname: Surya surname: Ramachandran fullname: Ramachandran, Surya organization: Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, India – sequence: 12 givenname: Nisha Asok surname: Kumar fullname: Kumar, Nisha Asok organization: Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, India – sequence: 13 givenname: Gigi surname: Thomas fullname: Thomas, Gigi organization: Regional Cancer Center, Thiruvananthapuram, India – sequence: 14 givenname: Thara surname: Somanathan fullname: Somanathan, Thara organization: Regional Cancer Center, Thiruvananthapuram, India – sequence: 15 givenname: Hiran K surname: Ravindran fullname: Ravindran, Hiran K organization: Amrita Institute of Medical Sciences, Kochi, India – sequence: 16 givenname: Kannan surname: Ranganathan fullname: Ranganathan, Kannan organization: Chennai Dental Research Foundation, Chennai, India – sequence: 17 givenname: Sudhakar Babu surname: Katakam fullname: Katakam, Sudhakar Babu organization: Manipal Acunova, Bengaluru, India – sequence: 18 givenname: Shivashankar surname: Parashuram fullname: Parashuram, Shivashankar organization: Manipal Acunova, Bengaluru, India – sequence: 19 givenname: Vijayvel surname: Jayaprakash fullname: Jayaprakash, Vijayvel organization: Roswell Park Cancer Institute, Buffalo, New York – sequence: 20 givenname: M Radhakrishna surname: Pillai fullname: Pillai, M Radhakrishna email: makuriakose@gmail.com, mrpillai@rgcb.res.in organization: Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, India. makuriakose@gmail.com mrpillai@rgcb.res.in |
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| Copyright | 2016 American Association for Cancer Research. |
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| Snippet | Oral leukoplakia is a potentially malignant lesion of the oral cavity, for which no effective treatment is available. We investigated the effectiveness of... |
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| SubjectTerms | Administration, Oral Adult Aged Antineoplastic Agents - administration & dosage Antineoplastic Agents - adverse effects Antineoplastic Agents - therapeutic use Biopsy Blood Cell Count Curcumin - administration & dosage Curcumin - adverse effects Curcumin - therapeutic use Cyclooxygenase 2 - metabolism Double-Blind Method Female Humans Leukoplakia, Oral - drug therapy Leukoplakia, Oral - pathology Male Middle Aged NF-kappa B - antagonists & inhibitors Placebos Time Factors Treatment Outcome |
| Title | A Randomized Double-Blind Placebo-Controlled Phase IIB Trial of Curcumin in Oral Leukoplakia |
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