Introduction: Magnesium plays a role in a large number of cellular metabolic reactions. Cetuximab is able to induce hypornagnesemia by interfering with magnesium (Mg2+) transport in the kidney. We designed this trial to investigate if Mg2+ serum level modifications may be related with clinical response and outcome in advanced colorectal cancer patients during treatment with cetuximab plus irinotecan. Experimental Design: Sixty-eight heavily pretreated metastatic colorectal cancer patients were evaluated for Mg2+ serum levels at the following time points: before; 6 hours; and 1, 7,14, 21, 50, and 92 days after the start of treatment. Results: Basal Mg2+ median levels were significantly decreased just 7 days after the first anticancer infusion and progressively decreased from the 7th day onward, reaching the highest significance at the last time point (P < 0.0001). Twenty-five patients showed a reduction in median Mg2+ circulating levels of at least 20% within the 3rd week after the first infusion. Patients with this reduction showed a response rate of 64.0% versus 25.6% in the nonreduced Mg2+ group. The median time to progression was 6.0 versus 3.6 months in the reduced Mg2+ group and in that without reduction, respectively (P < 0.0001). Overall survival was longer in patients with Mg2+ reduction than in those without (10.7 versus 8.9 months). Conclusions: Our results confirm that cetuximab treatment may induce a reduction of Mg2+ circulating levels and offer the first evidence that Mg2+ reduction may represent a new predictive factor of efficacy in advanced colorecial cancer patients treated with cetuximab plus irinotecan.

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

Vincenzi B;Santini D;Battistoni F;Rocci L;Beomonte Zobel B;Dicuonzo G;Tonini G
2008-01-01

Abstract

Introduction: Magnesium plays a role in a large number of cellular metabolic reactions. Cetuximab is able to induce hypornagnesemia by interfering with magnesium (Mg2+) transport in the kidney. We designed this trial to investigate if Mg2+ serum level modifications may be related with clinical response and outcome in advanced colorectal cancer patients during treatment with cetuximab plus irinotecan. Experimental Design: Sixty-eight heavily pretreated metastatic colorectal cancer patients were evaluated for Mg2+ serum levels at the following time points: before; 6 hours; and 1, 7,14, 21, 50, and 92 days after the start of treatment. Results: Basal Mg2+ median levels were significantly decreased just 7 days after the first anticancer infusion and progressively decreased from the 7th day onward, reaching the highest significance at the last time point (P < 0.0001). Twenty-five patients showed a reduction in median Mg2+ circulating levels of at least 20% within the 3rd week after the first infusion. Patients with this reduction showed a response rate of 64.0% versus 25.6% in the nonreduced Mg2+ group. The median time to progression was 6.0 versus 3.6 months in the reduced Mg2+ group and in that without reduction, respectively (P < 0.0001). Overall survival was longer in patients with Mg2+ reduction than in those without (10.7 versus 8.9 months). Conclusions: Our results confirm that cetuximab treatment may induce a reduction of Mg2+ circulating levels and offer the first evidence that Mg2+ reduction may represent a new predictive factor of efficacy in advanced colorecial cancer patients treated with cetuximab plus irinotecan.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12610/2921
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