Curcumin combined with FOLFOX chemotherapy is safe and tolerable in patients with metastatic colorectal cancer in a randomized phase IIa trial.

Background: Curcumin is the main active ingredient of the spice turmeric, investigated extensively for putative anti-cancer properties. Objective: This phase IIa open-labelled randomized controlled trial aimed to assess safety, efficacy, quality of life, neurotoxicity, curcuminoids, and C-X-C-motif chemokine ligand 1 (CXCL1) in patients receiving folinic acid/5-fluorouracil/oxaliplatin chemotherapy (FOLFOX) compared to FOLFOX + 2 g daily oral curcumin (CUFOX). Methods: Twenty eight patients aged >18 with a histological diagnosis of metastatic colorectal cancer were randomized (1:2) to receive either FOLFOX or CUFOX. Safety was assessed by Common Toxicity Criteria-Adverse Event (CTC-AE) reporting, and efficacy via progression free survival (PFS) and overall survival (OS). Quality of life and neurotoxicity were assessed using questionnaires (European Organization for Research and Treatment Quality of life (EORTC QLQ-C30) and Functional Assessment of Cancer Treatment-Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-NTX)). Plasma curcuminoids were determined with liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS/MS) and CXCL1 by enzyme-linked immunosorbent assay (ELISA). Results: Addition of daily oral curcumin to FOLFOX chemotherapy was safe and tolerable (primary outcome). Similar adverse event profiles were observed for both arms. In the intention to treat population, the hazard ratio for PFS was 0.57 (0.24, 1.36) (P = 0.2) (median of 171 vs 291 days for FOLFOX and CUFOX respectively), and for OS was 0.34 (0.14, 0.82) (P = 0.02) (median of 200 vs 502 days for FOLFOX and CUFOX respectively). There was no significant difference between arms for quality of life (P = 0.248) or neurotoxicity (P = 0.223). Curcumin glucuronide was detectable at levels >1.00 pmol/mL in 15 of 18 patients receiving CUFOX. Curcumin did not significantly alter CXCL1 over time (P = 0.712). Conclusions: Curcumin is a safe and tolerable adjunct to FOLFOX chemotherapy in patients with metastatic colorectal cancer. Trial registration was with ClinicalTrials.gov (NCT01490996) and the European Drug Regulating Authorities (EudraCT 2011-002289-19).