Melphalan monitoring during hyperthermic perfusion of isolated limb for melanoma: pharmacokinetic study and 99mTc-albumin microcolloid technique.
BACKGROUND
The kinetics of melphalan leakage from extracorporeal fluid to the peripheral blood was studied in ten patients undergoing hyperthermic isolation perfusion of the lower limbs as an adjuvant treatment in high-risk melanoma.


METHODS
Systemic leakage was monitored by a new technique using 99mTc-albumin microcolloid. Serial samples were drawn from a peripheral vein and from the perfusion circuit during surgical treatment and analysed by HPLC.


RESULTS
The leakage measured with 99mTc-albumin microcolloid ranged from 1.5 to 18%/h (mean 8%/h). The average concentrations in the perfusate were 200-300-fold those found in the systemic circulation. A good correlation (R=0.945) was obtained between systemic AUC (0 to 1 hour) and leakage measured through the 99mTc procedure. Negligible toxicity was found and the survival rate yielded 92% of objective response.


CONCLUSIONS
By studying the pharmacokinetic data of melphalan in the circuit and in the systemic circulation, we were able to validate the 99mTc procedure used during clinical perfusion. Moreover, considering the efficiency of the system as well as the minimum toxicity and the high survival rate, a reduction of perfusion time may be considered.
Cattel
L
L
Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Italy. cattel@pharm.unito.it
Buffa
E
E
De Simone
M
M
Cesana
P
P
Novello
S
S
Dosio
F
F
Ceruti
M
M
D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D003102:Colloids / Q000493:pharmacokinetics; D003131:Combined Modality Therapy; D016903:Drug Monitoring / Q000379:methods; D004355:Drug Stability; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000378:metabolism; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D008099:Liver / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism* / Q000628:therapy; D008558:Melphalan / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013668:Technetium Tc 99m Aggregated Albumin / Q000493:pharmacokinetics
D018906:Antineoplastic Agents, Alkylating; D003102:Colloids; D019275:Radiopharmaceuticals; D013668:Technetium Tc 99m Aggregated Albumin; D008558:Melphalan