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.
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.
Authors: Amanda K Raymond; Georgia M Beasley; Gloria Broadwater; Christina K Augustine; James C Padussis; Ryan Turley; Bercedis Peterson; Hilliard Seigler; Scott K Pruitt; Douglas S Tyler Journal: J Am Coll Surg Date: 2011-04-13 Impact factor: 6.113
Authors: Georgia M Beasley; Ketan Sharma; Joyce Wong; Mike Miller; Ryan S Turley; Michael Lidsky; Melanie Masoud; Mark W Dewhirst; Paul J Mosca; Jonathan S Zager; Douglas S Tyler Journal: Cancer Date: 2012-06-06 Impact factor: 6.860
Authors: N McMahon; T Y Cheng; G M Beasley; I Spasojevic; W Petros; C K Augustine; P Zipfel; J C Padussis; G Sanders; Douglas S Tyler Journal: Ann Surg Oncol Date: 2009-01-30 Impact factor: 5.344