Marked variability of melphalan plasma drug levels during regional hyperthermic isolated limb perfusion

Tsung Yen Cheng, Elizabeth Grubbs, Omar Abdul-Wahab, Szu Yun Leu, Chen Fang Hung, William Petros, Thomas Aloia, Randy Fedrau, Scott Pruitt, Michael Colvin, Henry Friedman, Douglas Tyler

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: Hyperthermic isolated limb perfusion (HILP) with melphalan as treatment for locally recurrent or in-transit malignant melanoma is frequently performed but the principle for calculating drug dosage remains poorly understood. Methods: This study examined the pharmacokinetic profile of 14 consecutive patients to determine what variables were associated with toxicity and tumor responses. Results: Marked fourfold variability was noted in patient plasma melphalan concentrations. We defined a factor - the ratio of estimated limb volume (Vesti) to melphalan volume of distribution (Vss), Vesti/Vss - that was much more strongly correlated with acute regional toxicity than either area under concentration-time curve or peak plasma concentration. In addition, we found that AUX2 was the best correlate of tumor response. Conclusions: Pharmacokinetic evaluation of prospective HILP trials is critical to not only understand response and toxicity outcomes but also to potentially improve the therapeutic index of regional perfusion.

Original languageEnglish (US)
Pages (from-to)460-467
Number of pages8
JournalAmerican Journal of Surgery
Volume186
Issue number5
DOIs
StatePublished - Nov 2003
Externally publishedYes

Fingerprint

Melphalan
Extremities
Perfusion
Pharmacokinetics
Pharmaceutical Preparations
Melanoma
Neoplasms
Therapeutics

Keywords

  • Limb perfusion
  • Melanoma
  • Melphalan
  • Pharmacokinetics
  • Volume of distribution

ASJC Scopus subject areas

  • Surgery

Cite this

Marked variability of melphalan plasma drug levels during regional hyperthermic isolated limb perfusion. / Cheng, Tsung Yen; Grubbs, Elizabeth; Abdul-Wahab, Omar; Leu, Szu Yun; Hung, Chen Fang; Petros, William; Aloia, Thomas; Fedrau, Randy; Pruitt, Scott; Colvin, Michael; Friedman, Henry; Tyler, Douglas.

In: American Journal of Surgery, Vol. 186, No. 5, 11.2003, p. 460-467.

Research output: Contribution to journalArticle

Cheng, TY, Grubbs, E, Abdul-Wahab, O, Leu, SY, Hung, CF, Petros, W, Aloia, T, Fedrau, R, Pruitt, S, Colvin, M, Friedman, H & Tyler, D 2003, 'Marked variability of melphalan plasma drug levels during regional hyperthermic isolated limb perfusion', American Journal of Surgery, vol. 186, no. 5, pp. 460-467. https://doi.org/10.1016/j.amjsurg.2003.07.019
Cheng, Tsung Yen ; Grubbs, Elizabeth ; Abdul-Wahab, Omar ; Leu, Szu Yun ; Hung, Chen Fang ; Petros, William ; Aloia, Thomas ; Fedrau, Randy ; Pruitt, Scott ; Colvin, Michael ; Friedman, Henry ; Tyler, Douglas. / Marked variability of melphalan plasma drug levels during regional hyperthermic isolated limb perfusion. In: American Journal of Surgery. 2003 ; Vol. 186, No. 5. pp. 460-467.
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AU - Abdul-Wahab, Omar

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AU - Hung, Chen Fang

AU - Petros, William

AU - Aloia, Thomas

AU - Fedrau, Randy

AU - Pruitt, Scott

AU - Colvin, Michael

AU - Friedman, Henry

AU - Tyler, Douglas

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AB - Background: Hyperthermic isolated limb perfusion (HILP) with melphalan as treatment for locally recurrent or in-transit malignant melanoma is frequently performed but the principle for calculating drug dosage remains poorly understood. Methods: This study examined the pharmacokinetic profile of 14 consecutive patients to determine what variables were associated with toxicity and tumor responses. Results: Marked fourfold variability was noted in patient plasma melphalan concentrations. We defined a factor - the ratio of estimated limb volume (Vesti) to melphalan volume of distribution (Vss), Vesti/Vss - that was much more strongly correlated with acute regional toxicity than either area under concentration-time curve or peak plasma concentration. In addition, we found that AUX2 was the best correlate of tumor response. Conclusions: Pharmacokinetic evaluation of prospective HILP trials is critical to not only understand response and toxicity outcomes but also to potentially improve the therapeutic index of regional perfusion.

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