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Evaluation of the relationship between cetuximab therapy and corrected QT interval changes in patients with advanced malignancies from solid tumors

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Abstract

Purpose

Greater scrutiny is being placed on developing a full understanding of potential cardiotoxicity of therapeutic agents, especially on the potential to prolong the QTc interval which can lead to arrhythmias such as torsade de pointes and sudden death. This trial was designed to specifically evaluate the effect, if any, of cetuximab on the QTc interval in patients with advanced solid tumors.

Methods

Cetuximab was administered as an initial dose of 400 mg/m2 on day 1 (week 1) followed by a maintenance dose of 250 mg/m2 weekly thereafter. ECG monitoring was performed at screening, baseline (week 1 preceding dosing), and during week 1 to 5 of treatment. Cetuximab concentration-to-QTc relationship was evaluated based on cetuximab serum samples obtained at the time of each ECG measurement to allow for accurate correlation between any observed QT/QTc changes and cetuximab serum concentration.

Results

At the recommended dose (400 mg/m2 on day 1 followed by 250 mg/m2 weekly), cetuximab had no clinically meaningful effect on QTc interval, PR or QRS intervals, or heart rate and there was no apparent concentration-dependent effect of cetuximab on any of these electrocardiogram parameters. Safety observations in patients treated with cetuximab in this study were consistent with the agent’s known safety profile.

Conclusion

These results suggest that cetuximab can be safely administered as a single agent without risk of effect on QTc interval.

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Acknowledgments

This study (NCT00698841) was sponsored by Bristol-Myers Squibb. The authors would like to acknowledge all the investigators, and their sites, participating in this study: Richy Agajanian, Vincent A. Armenio, John Deeken, Lourdes J. Feliciano, Troy H. Guthrie Jr, Jayne Gurtler, Donald W. Hill, Charles W. Hollen, Haresh S. Jhangjiani, Lawrence P. Leichman, Andre K.D. Liem, Hima Bindu Lingham, An D. Nguyen, Craig H. Reynolds, and. Brian J. Shimkus. The authors would also like to thank the patients as well as their families and caregivers. Medical writing and editorial support were provided by Jamie H. Zhang, PhD, an employee of Bristol-Myers Squibb.

Conflict of interest

Authors JFD, BS, AL, DH, and JG declared no conflict of interest. Authors EB, LT, and HL are employed by Bristol-Myers Squibb (BMS) and may own stock. Authors OT and SZ were both employed by BMS at time of study conduct and during early stages of manuscript preparation, but have since left that employment.

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Authors and Affiliations

  1. Lombardi Comprehensive Cancer Center, Georgetown University, 3800 Reservoir Road, NW, Washington, DC, 20007, USA

    J. F. Deeken

  2. Austin Cancer Centers, Austin, TX, USA

    B. Shimkus

  3. Pacific Shores Medical Group, Long Beach, CA, USA

    A. Liem

  4. Tri-Valley Cancer Research and Treatment Center, Casa Grande, AZ, USA

    D. Hill

  5. Metairie Oncologists, LLC, Metairie, LA, USA

    J. Gurtler

  6. Bristol-Myers Squibb Company, Wallingford, CT, USA

    E. Berghorn, H. Lu & O. Trifan

  7. Bristol-Myers Squibb Company, Lawrenceville, NJ, USA

    L. Townes & S. Zhang

Authors
  1. J. F. Deeken
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  2. B. Shimkus
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  3. A. Liem
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  8. H. Lu
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Corresponding author

Correspondence to J. F. Deeken.

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Deeken, J.F., Shimkus, B., Liem, A. et al. Evaluation of the relationship between cetuximab therapy and corrected QT interval changes in patients with advanced malignancies from solid tumors. Cancer Chemother Pharmacol 71, 1473–1483 (2013). https://doi.org/10.1007/s00280-013-2146-5

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  • DOI: https://doi.org/10.1007/s00280-013-2146-5

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