Early magnesium reduction in advanced colorectal cancer patients treated with cetuximab + irinotecan as predictive factor of efficacy and outcome

Abstract

4106 Background: Magnesium plays a role in a large number of cellular metabolic reactions. Cetuximab is able to induce hypomagnesaemia by interfering with magnesium (Mg2+) transport in the kidney. We designed this trial to investigate if Mg2+ serum levels modifications may be related with clinical response and outcome in advanced colorectal cancer (CRC) patients during treatment with cetuximab plus irinotecan (CTX+CPT11). Methods: 91 pretreated metastatic CRC patients were evaluated for Mg2+ serum levels. The following time-points were analyzed: before 1, 7, 14, 21, 50 and 92 days after the start of treatment. Results: basal Mg2+ median levels were significantly decreased just seven days after the first anticancer infusion and progressively decreased along all the time points, reaching the highest significance at the last time point (P<0.0001). 46 patients showed a reduction in median Mg2+ circulating levels of at least 20% within the third week after the first infusion respect to the basal time point. Patients with this reduction showed a response rate of 68.0% vs 29.5% in the non reduced Mg2+ group. The median time to progression (TTP) was 6.7 vs 3.9 months in the reduced Mg2+ group and in that without, respectively (p<0.0001). Overall survival (OS) was longer in patients with Mg2 reduction than in those without (10.5 vs 7.5 months, p=0.02). Conclusions: our results confirm that cetuximab treatment may induce a reduction of Mg2+ circulating levels and offer the first evidence that early Mg2+ reduction may represents a new predictive factor of efficacy in heavily pretreated advanced CCR patients treated with CTX+CPT11. No significant financial relationships to disclose.