Hypomagnesemia is a reliable predictor for efficacy of anti-EGFR monoclonal antibody used in combination with first-line chemotherapy for metastatic colorectal cancer

Cancer Chemother Pharmacol. 2016 Jun;77(6):1209-15. doi: 10.1007/s00280-016-3039-1. Epub 2016 Apr 22.

Abstract

Purpose: Anti-EGFR monoclonal antibody is effective for KRAS wild-type metastatic colorectal cancer (mCRC), but frequently causes several adverse reactions, including hypomagnesemia and skin disorders. The present study was designed to investigate the relationship between the incidence of adverse reactions and therapeutic effects in mCRC patients receiving anti-EGFR monoclonal antibody in combination with first-line chemotherapy.

Methods: Forty-three mCRC patients who received cetuximab or panitumumab between April 2012 and December 2015 were the subjects of the present study. All patients were pretreated with oral minocycline in combination with skin treatment using moisturizer for prevention of skin rash. Hypomagnesemia and acneiform rash were graded according to the Common Terminology Criteria for Adverse Events, version 3.0. Overall response rate (ORR) and time to treatment failure (TTF) were compared between patients with and without these adverse events.

Results: The incidence rates of hypomagnesemia and acneiform rash were 32.6 % (grade 1: 20.9 %, grade 2: 11.6 %) and 93.0 % (grade 1: 41.9 %, grade 2: 41.9 %, grade 3: 9.3 %), respectively. ORR was significantly higher in patients with hypomagnesemia than in those without it (71.4 vs 34.5 %, P = 0.048). Median TTF tended to be longer, though not significantly, in patients with hypomagnesemia than in those without it. However, no significant difference in both ORR and median TTF was observed between patients with and without acneiform rash.

Conclusion: Hypomagnesemia may become a predicting factor for therapeutic effects of anti-EGFR monoclonal antibody in mCRC patients.

Keywords: Acneiform rash; Anti-EGFR monoclonal antibody; Hypomagnesemia; Metastatic colorectal cancer; Overall response rate; Time to treatment failure.

MeSH terms

  • Acneiform Eruptions / chemically induced*
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cetuximab / administration & dosage
  • Cetuximab / adverse effects
  • Cetuximab / therapeutic use
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • ErbB Receptors / antagonists & inhibitors*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Magnesium / administration & dosage
  • Magnesium / blood*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Panitumumab
  • Predictive Value of Tests
  • Response Evaluation Criteria in Solid Tumors
  • Treatment Failure

Substances

  • Antibodies, Monoclonal
  • Panitumumab
  • EGFR protein, human
  • ErbB Receptors
  • Magnesium
  • Cetuximab