Melphalan tissue concentrations in patients treated with regional isolated perfusion for melanoma of the lower limb.
In 14 consecutive patients with recurrent melanoma of the lower limb a total of 35 biopsies were taken at the end of perfusion treatment to assess melphalan tissue concentrations in tumour, skin/subcutis and muscle tissue. In tumour tissue (n = 12) the mean melphalan concentration was 6.8 micrograms g-1, which was significantly higher than that of healthy skin/subcutis (3.2 micrograms g-1; n = 10), but equal to that of muscle tissue (6.5 micrograms g-1; n = 13). The correlation between melphalan concentration in the tissues and the concentration in the perfusate was studied. The latter was assessed in the form of melphalan peak concentration and the area under the curve (AUC0-->60) of the melphalan concentration-time curve. Tumour concentration proved to be correlated linearly with AUC0-->60 (R = 0.6, P = 0.002) and muscle concentration with melphalan peak concentration (R = 0.8, P = 0.04). There was no relation between skin/subcutis concentrations and the perfusate parameters. Further research is warranted to study the relationship between melphalan tissue concentration, tumour response and regional toxicity.
Department of Surgery, The Netherlands Cancer Institute (Antoni van Leeuwenhoek Huis), Amsterdam.
J M
JM
Klaase
B B
BB
Kroon
J H
JH
Beijnen
G W
GW
van Slooten
J A
JA
van Dongen
D010478:Chemotherapy, Cancer, Regional Perfusion; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007866:Leg; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism*; D008558:Melphalan / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism*
D008558:Melphalan