BACKGROUND:Isolated limb infusion (ILI) is an effective and minimally invasive treatment option for delivering regional chemotherapy in patients with metastatic melanoma confined to a limb. Recurrent or progressive disease after an ILI, however, presents a challenge for further treatment. The value of repeat ILI in this situation has not been well documented.METHODS:Forty‐eight patients were identified who had been treated with a repeat ILI. In all patients, a cytotoxic combination of melphalan and actinomycin D was used.RESULTS:The median time between the 2 procedures was 11 months. The complete response (CR) rate after repeat ILI was 23%, compared with 31% after the initial ILI (P = .36). The overall response was 83%, compared with 75% after the first procedure (P = .32). The median duration of response was 11 months (10 months for patients with CR; P = .80), and median survival was 38 months. In those patients achieving a CR, the median survival was 68 months (P = .003). Toxicity after repeat ILI was increased, with 20 patients experiencing Wieberdink grade III limb toxicity (considerable erythema and edema with blistering) and 5 patients experiencing grade IV toxicity (threatened or actual compartment syndrome), whereas after the initial ILI these toxicity grades occurred in 14 patients and 1 patient, respectively (P = .03). No patient experienced grade V toxicity (requiring amputation).CONCLUSIONS:Repeat ILI is an attractive treatment option to achieve limb salvage in patients with inoperable recurrent or progressive melanoma after a previous ILI. It can be associated with significant short‐term regional toxicity, but is well tolerated by most patients, with satisfactory response rates. Cancer 2009. © 2009 American Cancer Society.

Elderly patients with advanced metastatic melanoma of the limb experience the same or lower toxicity after ILI compared with younger patients while response rates, limb recurrence free interval, survival, and morbidity are similar. ILI is an attractive alternative to the more laborious ILP, especially for older patients.

Minimally invasive ILI can effectively be used as palliative treatment to provide local tumor control and limb salvage in stage IV melanoma patients with advanced, symptomatic limb disease.

Amputation following upper extremity ILI is more common compared to lower extremity ILI. Amputation may provide effective long-term palliation in selected patients when there is extensive inoperable progressive or recurrent disease after ILI.