The role of regional chemotherapy for advanced limb melanoma in the era of potentially effective systemic therapies.

To review the current role of regional chemotherapy in the management of advanced limb melanoma. Articles reporting the results of isolated limb infusion (ILI) were identified by performing a comprehensive literature search using the PubMed database. Keywords included isolated limb infusion, in-transit melanoma and melphalan. No publication date restrictions were applied. ILI data were compared with those from current systemic therapy clinical trials and the previously reviewed isolated limb perfusion (ILP) literature. Regional chemotherapy is today required in fewer patients because effective systemic therapies now provide an alternative treatment for those who develop extensive local melanoma recurrence or in-transit metastases (ITMs). However, regional chemotherapy may be a valuable treatment option when the side-effects of systemic therapies are of concern, or after systemic treatment failure. ILP achieves overall response rates (ORRs) of 64-100% and complete response rates (CRRs) of 25-89%. ILI achieves ORRs of 41-91% and CRRs of 6-39%. ILP and ILI can have a low risk of serious morbidity. Early results from treatment with ILP or ILI in conjunction with systemic immune therapies suggest that these modalities can be safely combined, which may be useful in patients with refractory limb disease. Regional chemotherapy remains important in the armamentarium of clinicians managing patients with unresectable limb melanoma and may be preferable in those who are frail, elderly or who are at high risk from complications of systemic therapies. The efficacy of combining regional chemotherapy with systemic immune therapy is currently being assessed.