Related Experiment Video
Updated: Aug 30, 2026
Minimally Invasive Isolated Limb Perfusion (MI-ILP) for Locally Advanced Melanomas and Sarcomas of the Extremity
Published on: January 31, 2025
Marked variability of melphalan plasma drug levels during regional hyperthermic isolated limb perfusion
Tsung-Yen Cheng1, Elizabeth Grubbs, Omar Abdul-Wahab
1Department of Surgery, Box 3118, Duke University Medical Center, Durham, NC 27710, USA.
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.
