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

Clin Cancer Res. 2008 Jul 1;14(13):4219-24. doi: 10.1158/1078-0432.CCR-08-0077.

Abstract

Introduction: Magnesium plays a role in a large number of cellular metabolic reactions. Cetuximab is able to induce hypomagnesemia by interfering with magnesium (Mg(2+)) transport in the kidney. We designed this trial to investigate if Mg(2+) 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 Mg(2+) 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 Mg(2+) 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 Mg(2+) 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 Mg(2+) group. The median time to progression was 6.0 versus 3.6 months in the reduced Mg(2+) group and in that without reduction, respectively (P < 0.0001). Overall survival was longer in patients with Mg(2+) reduction than in those without (10.7 versus 8.9 months).

Conclusions: Our results confirm that cetuximab treatment may induce a reduction of Mg(2+) circulating levels and offer the first evidence that Mg(2+) reduction may represent a new predictive factor of efficacy in advanced colorectal cancer patients treated with cetuximab plus irinotecan.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives*
  • Cetuximab
  • Colorectal Neoplasms / drug therapy*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Irinotecan
  • Magnesium / chemistry
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Irinotecan
  • Magnesium
  • Cetuximab
  • Camptothecin