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

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. This study examined the pharmacokinetic profile of 14 consecutive patients t...

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Bibliographic Details
Published in:The American journal of surgery 2003-11, Vol.186 (5), p.460-467
Main Authors: 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
Format: Article
Language:English
Subjects:
Antineoplastic Agents, Alkylating - administration & dosage
Antineoplastic Agents, Alkylating - blood
Antineoplastic Agents, Alkylating - therapeutic use
Biological and medical sciences
Chemotherapy
Chemotherapy, Cancer, Regional Perfusion - methods
Dermatology
Drug dosages
Extremities
Female
Heat exchangers
Humans
Hyperthermia, Induced
Limb perfusion
Male
Medical sciences
Medical treatment
Melanoma
Melanoma - drug therapy
Melphalan
Melphalan - administration & dosage
Melphalan - blood
Melphalan - therapeutic use
Middle Aged
Pharmacokinetics
Plasma
Skin cancer
Skin Neoplasms - drug therapy
Temperature
Tumors of the skin and soft tissue. Premalignant lesions
Volume of distribution
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Summary: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. This study examined the pharmacokinetic profile of 14 consecutive patients to determine what variables were associated with toxicity and tumor responses. 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. 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.
ISSN:0002-9610
1879-1883
DOI:10.1016/j.amjsurg.2003.07.019