Abstract CT124: A phase II randomized double blind study of curcumin with preoperative capecitabine and radiation therapy followed by surgery for rectal cancer

Introduction: In vivo studies show that curcumin, a component of turmeric (Curcuma longa), inhibits signal transduction pathways involved in tumor growth and angiogenesis, induces apoptosis and potentiates the radioresponse of cancer cells by inducing NF-kB activity. However no study has validated its anti-tumor effect in patients undergoing cancer treatment. We performed a randomized double blinded study in patients with locally advanced rectal cancer to assess the efficacy of a combination of capecitabine and radiation therapy with or without curcumin, using pathological complete response (pCR) rate as a surrogate for overall clinical outcomes. Patients and Methods: Between September, 2008 and September, 2010, patients with biopsy-proven, locally advanced adenocarcinoma of the rectum were enrolled and randomized to placebo and curcumin treatment arms in a 1:2 ratio. All patients received pre-operative radiation therapy (50.4 Gy/28 fractions for 5-6 weeks) along with concurrent capecitabine (825 mg/m2 orally twice daily, only on days of radiation) followed by surgery after 6 weeks. Curcumin or placebo capsules (4 g orally, twice daily) were given throughout the chemoradiation therapy period and until surgery, typically 6 weeks later. Patients were evaluated at baseline, weekly during chemoradiation and just before surgery using the MD Anderson symptom inventory (MDASI) and Brief Fatigue Inventory (BFI) questionnaires. In addition, weekly clinical assessment and monitoring of hematological and biochemical parameters was done throughout the treatment course to evaluate treatment-related toxicity. The pharmacokinetics of curcumin was studied using blood samples taken before and one hour after curcumin intake during the second week of chemoradiation. The primary target outcome was pCR evaluated at the time of surgery. This study is registered with Clinicaltrials.gov, number NCT00745134. Results: 22 patients were enrolled in the study and 15 received curcumin. The median age was 61 years and majority were males (13, 59%). The median serum curcumin concentrations before and one hour after curcumin intake did not differ significantly (p = 0.33) and were 3.04 ng/mL (range, 1.24 to 18.88) and 3.32 ng/mL (range, 0.84 to 5.36) respectively. pCR was seen in two patients in the placebo arm and one patient in the curcumin arm (p = 0.23). Acute toxicity was relatively uncommon in both groups: grade 2 diarrhea (1, 7%), grade 2 dermatitis (5, 33%) and grade 3 diarrhea (1, 7%) in the curcumin arm; grade 2 dermatitis (1, 14%) and grade 3 diarrhea (1, 14%) in the placebo arm. Conclusion: Addition of curcumin to capecitabine and radiation therapy did not increase the rate of pCR in patients with rectal cancer. The low bioavailability of curcumin preparation used could explain the lack of efficacy noted in this study. Citation Format: Awalpreet S. Chadha, Sushovan Guha, Sunil Krishnan. A phase II randomized double blind study of curcumin with preoperative capecitabine and radiation therapy followed by surgery for rectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT124. doi:10.1158/1538-7445.AM2015-CT124