Isolated limb infusion for melanoma: A simple but effective alternative to isolated limb perfusion

Multiple limb recurrences sometimes occur in a patient who has had previous surgical treatment for a melanoma on that limb, but who is completely well otherwise, with no evidence of systemic metastasis. In such patients a satisfactory method of local disease control is required, because many of them will remain disease free at systemic sites for prolonged periods, some indefinitely. For example, in a study that reported long-term outcome following successful treatment of large or multiple limb recurrences by isolated limb perfusion (ILP) with cytotoxic drugs, approximately half the patients in whom a complete response (CR) in the limb had been achieved were alive and free of disease at any site after a median follow-up period of 33 months [1]. If limb recurrences are numerous and widespread but are small and superficial (i.e., cutaneous only), simple and non-invasive treatment modalities such as cryotherapy, electrodessication, or laser ablation are often effective [2]. If the limb recurrences are subcutaneous or even in muscle but are localized and easily managed by surgical excision with or without skin grafting, this is the treatment of choice. There remains a group of patients, however, who have multiple melanoma recurrences confined to a limb but in whom the disease is not able to be treated by such simple measures. It is in these patients that regional chemotherapy techniques such as ILP should be considered. In clinical use for nearly four decades [3], ILP with melphalan (L-phenylalanine mustard, L-PAM) has been demonstrated in many series to be an effective form of treatment for metastatic melanoma confined to a limb [4,5], and technical aspects of the technique are well documented [6]. Conventional ILP induces a CR in 7– 90% (median 46%) of limbs, and a partial response (PR) in 0–44% (median 34%), with a median response duration of 9–19 months in patients who have achieved a CR [1,4]. However, ILP is a complex and invasive procedure that is available only in specialized centers, and is generally considered inappropriate in patients who are elderly or who have serious co-morbidities [7]. A minimally invasive and simplified procedure called ‘‘isolated limb infusion’’ (ILI) was developed at the Sydney Melanoma Unit (SMU) with the objective of obtaining the benefits of ILP without incurring its major disadvantages [8,9]. ILI is essentially a low flow ILP performed without oxygenation via percutaneously inserted catheters. Its aim is to deliver a high dose of a cytotoxic drug or drugs locoregionally whilst the limb is isolated from the systemic circulation by a pneumatic tourniquet. Although the limb tissues are exposed to the cytotoxic agents for a relatively short period (normally 30 min) during ILI, there is adequate cellular uptake for tumor cell killing to be achieved in most patients [10]. Technical aspects of the ILI procedure are described and discussed elsewhere [9,11,12]. Briefly, arterial and venous catheters are inserted into the affected limb via the contralateral groin, using standard radiological techniques. This preliminary procedure is performed in the radiology department, using local anesthesia. The patient is then transferred to the operating room, and given a general anesthetic. The arterial and venous catheters are