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Optimizing Melphalan Pharmacokinetics in Regional Melanoma Therapy: Does Correcting for Ideal Body Weight Alter Regional Response or Toxicity?

  • Melanomas
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

This study aims to determine what effect correcting melphalan dosing for ideal body weight (IBW) has on toxicity and response in isolated limb infusion (ILI) in patients with advanced extremity melanoma.

Methods

This was an open observational study examining whether correcting the melphalan dose for IBW will influence response and toxicity in patients undergoing ILI for advanced extremity melanoma in 41 patients undergoing 42 procedures (13 without correction for IBW; and 29 with correction for IBW). Melphalan pharmacokinetics, limb toxicity, serologic toxicity, and response at 3 months were compared.

Results

The corrected group had a lower estimated limb volume (V esti) to melphalan volume at steady state (V ss) (P < .0001) ratio as well as lower incidence of grade ≥3 regional toxicity, serologic toxicity, and compartment syndrome (P = .0249, P = .027, P = .02). There was a positive correlation of V esti/V ss to toxicity (P = .0127, r = .382). No significant difference in response (P = .3609) between the groups was found, although there was a trend of association between V esti/V ss and response (P = .051, r = .3383).

Conclusions

Correcting for IBW in ILI lowers toxicity without significantly altering response rates.

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Acknowledgments

This work was supported in part by the Duke Melanoma Research Fund and a Grant from the Institute of Genomic Sciences and Policy at Duke University Medical Center (DT) and the NIH/NCI Duke Comprehensive Cancer Center Core Grant (5-P30-CA14236-29).

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Authors and Affiliations

  1. Department of Surgery, Duke University Medical Center, Durham, NC, USA

    N. McMahon BS, G. M. Beasley MD, C. K. Augustine PhD, P. Zipfel PhD, J. C. Padussis MD, G. Sanders BSN & Douglas S. Tyler MD

  2. Division of General Surgery, Koo-Foundation Sun Yat-Sen Cancer Center, National Yang Ming University, Taipei, Taiwan

    T. Y. Cheng MD

  3. Department of Medicine, Duke University Medical Center, Durham, NC, USA

    I. Spasojevic PhD

  4. Dept. of Basic Pharm. Sciences, School of Pharmacy and Cancer Center, West Virginia University, Morgantown, WV, USA

    W. Petros PhD

  5. VA Medical Center, Durham, NC, USA

    C. K. Augustine PhD, P. Zipfel PhD, J. C. Padussis MD & Douglas S. Tyler MD

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  1. N. McMahon BS
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  2. T. Y. Cheng MD
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  3. G. M. Beasley MD
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  4. I. Spasojevic PhD
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  5. W. Petros PhD
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  6. C. K. Augustine PhD
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  7. P. Zipfel PhD
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  8. J. C. Padussis MD
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  9. G. Sanders BSN
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  10. Douglas S. Tyler MD
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Corresponding author

Correspondence to Douglas S. Tyler MD.

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McMahon, N., Cheng, T.Y., Beasley, G.M. et al. Optimizing Melphalan Pharmacokinetics in Regional Melanoma Therapy: Does Correcting for Ideal Body Weight Alter Regional Response or Toxicity?. Ann Surg Oncol 16, 953–961 (2009). https://doi.org/10.1245/s10434-008-0288-1

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