A clinical and pharmacokinetic study of isolated limb perfusion with heat and melphalan for melanoma

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Abstract
The pharmacokinetics of isolated limb perfusion were studied to see what melphalan concentrations were achieved and how effective the isolation was. Twenty-eight patients received 32 limb perfusions with heat and melphalan for locally recurrent or level V melanoma. Melphalan was given 0.75 mg/kg for axillary/popliteal or 1.2 mg/kg for femoral perfusions with heat (perfusate 42°C, limb 40°C) for 1 hour. Melphalan concentratives were measured by high-performance liquid chromatography in seven patients. Peak perfusate melphalan concentrations were 6.1 to 115 mg/ml, which was one to two logs higher than peak systemic concentratives of melphalan. Isolation of the perfusate circuit from the systemic circulation was better for axillary and popliteal perfusions than for femoral perfusions (P < 0.05). Complete responses were seen in 81% of evaluable patients; long-term local control was achieved in most patients, although many developed hematogenous metastases. Toxicity included erythema and edema in all, mild leukopenia in two, neuropathy in two, and amputation was required in one patient. Improvements in surgical technique include regional anesthesia to reduce vasospasms and transcutaneous measurement of fluorescein to measure leak. Perfusion with heat and melphalan remains the treatment of choice for in-transit metastases from melanoma.