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

• Published in: Annals of surgical oncology Vol. 16; no. 4; pp. 953 - 961
• Main Authors: McMahon, N., Cheng, T. Y., Beasley, G. M., Spasojevic, I., Petros, W., Augustine, C. K., Zipfel, P., Padussis, J. C., Sanders, G., Tyler, Douglas S.
• Format: Journal Article
• Language: English
• Published: New York Springer-Verlag 01.04.2009; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating - administration & dosage; Antineoplastic Agents, Alkylating - pharmacokinetics; Body Weight; Chemotherapy, Cancer, Regional Perfusion; Dose-Response Relationship, Drug; Extremities; Female; Humans; Male; Medicine; Medicine & Public Health; Melanoma - drug therapy; Melanomas; Melphalan - administration & dosage; Melphalan - pharmacokinetics; Middle Aged; Oncology; Skin Neoplasms - drug therapy; Surgery; Surgical Oncology; Isolate Limb Infusion; Actual Body Weight; Limb Volume; Ideal Body Weight; Melphalan
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-008-0288-1

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.