A Phase II Randomized Double Blinded Trial Evaluating the Efficacy of Curcumin With Pre-operative Chemoradiation for Rectal Cancer

Authors

Jillian R Gunther
Awalpreet S Chadha
Sushovan Guha
Gottumukkala S Raju
Dipen M Maru
Mark F Munsell
Yan Jiang
Peiying Yang
Edd Felix
Marilyn Clemons
Geena George Mathew
Pankaj K Singh
John M Skibber
Miguel A Rodriguez-Bigas
George J Chang
Cathy Eng
Marc E Delclos
Christopher H Crane
Prajnan Das
Sunil Krishnan

Publication Date

12-1-2022

Journal

Journal of Gastrointestinal Oncology

Abstract

Background

In vivo studies demonstrate that curcumin increases radioresponse of colorectal cancers. To demonstrate efficacy in humans, we performed a randomized double-blind study of locally advanced rectal cancer (LARC) patients receiving pre-operative chemoradiation therapy (CRT) ± curcumin. We used pathologic complete response (pCR) rate as a surrogate for clinical outcome.

Methods

From 2008–2010, LARC patients were randomized to placebo/curcumin in a 1:2 ratio. Patients received CRT [50.4 gray in 28 fractions; capecitabine (825 mg/m² twice daily)] followed by surgery. Curcumin (4 grams orally, twice daily) or placebo was given throughout CRT and 6 weeks afterward. Toxicity was monitored weekly. Blood samples taken pre- and 1-hour post-ingestion and tissue biopsies (both collected at CRT week 2) were analyzed for pharmacokinetics. The primary outcome was surgical pCR rate.

Results

Of 22 enrolled patients, 15 received curcumin. Median age was 61 years and the majority were male (n=13; 59%). The median serum curcumin concentrations before (3.04 ng/mL; range, 1.24–18.88 ng/mL) and 1 hour after (3.32 ng/mL; range, 0.84–5.36 ng/mL) curcumin intake did not differ significantly (P=0.33). Serum curcumin concentrations both increased and decreased 1-hour post-administration (range as percentage of baseline: 8.8–258.1%). Twelve curcumin patient tissue biopsies had median curcumin concentration of 33.7 ng/mg tissue (range, 0.1–4,765.7 ng/mg). Two placebo and 1 curcumin patient achieved pCRs (P=0.18). One grade 3 toxicity (infection) was experienced.

Conclusions

The addition of curcumin to CRT did not increase pCR rates for LARC patients. The unpredictable bioavailability of curcumin contributes to continued uncertainties regarding curcumin efficacy.

Keywords

Locally advanced rectal cancer (LARC), chemoradiation, curcumin

Comments

ClinicalTrials.gov identifier: NCT00745134.