Dietary methionine restriction with FOLFOX regimen as first line therapy of metastatic colorectal cancer: a feasibility study.

The methionine (MET) dependency of tumor cells opens interesting perspectives for targeting tumor cells and potentiating chemotherapy treatment, like 5-fluorouracil (5-FU) and platinum compound. Since MET deprivation can individually potentiate the different chemotherapeutic agents used in the 48-hour combined regimen of 5-FU, leucovorin and oxaliplatin (FOLFOX) regimen, we initiated a feasibility study associating dietary MET restriction with the FOLFOX regimen in patients with metastatic colorectal cancer. (i) To evaluate the depletion in the plasma MET concentration, and (ii) to assess the feasibility of this combination. Eleven patients were enrolled in this study. They received a median number of 3 two-week cycles of a MET-free diet (3 consecutive days) and FOLFOX6 regimen. The plasma MET concentration was reduced by dietary MET restriction, with a depletion of 58% on the 1st day of MET-free diet. Indeed, we demonstrated the feasibility and good tolerance (nutritional status and toxicity) of the association of a MET-free diet with the FOLFOX regimen. Despite good compliance to the diet, this study revealed the difficulty of administering this combination during further months. Among the 4 patients evaluable for response, 3 experienced a partial response and 1 patient a disease stabilization.