Isolated limb infusion with hyperthermia and chemotherapy for advanced limb malignancy: factors influencing toxicity

The isolated limb infusion (ILI) technique is a simpler and less invasive alternative to isolated limb perfusion, which allows regional administration of high-dose chemotherapy to patients with advanced melanoma and other malignancies restricted to a limb.

Patients from two institutions, treated by ILI between 1998 and 2009 for extensive disease restricted to a limb, were included. The cohort included 31 patients with melanoma who presented with in-transit metastases or an extensive primary lesion, one patient with squamous cell carcinoma and another with epithelioid sarcoma not suitable for local surgical treatment.

A complete response was achieved in 26.3% of patients and a partial response in 52.6%. Toxicity was assessed according to the Wieberdink limb toxicity scale. Grade II toxicity was noted in 39.5% of patients, grade III in 50% and grade IV in 10.5%. Toxicity was correlated with the results of a number of clinical and laboratory tests. The toxicity of melphalan and actinomycin D was dose-dependent. For melphalan, the relationship between toxicity and mean dose was as follows: grade II--34.7 mg; grades III and IV--47.5 mg (P = 0.012). The relationship between toxicity and maximum serum creatine phosphokinase (CPK) was as follows: grade II--431.5 U/L; grades III and IV--3228 U/L (P = 0.010).

Toxicity after ILI is dose-dependent and serum CPK correlates with toxicity.