Isolated limb perfusion for malignant melanoma: systematic review on effectiveness and safety

Abstract

Background: Isolated limb perfusion (ILP) involves the administration of chemotherapy drugs directly into a limb involved by locoregional metastases. Unresectable locally advanced melanoma of the limbs represents one of the clinical settings in which ILP has demonstrated benefits.

Methods: A systematic review of the literature on ILP for patients with unresectable locally advanced melanoma of the limbs was conducted. MEDLINE, EMBASE, and Cochrane database searches were conducted to identify studies fulfilling the following inclusion criteria: hyper- or normothermic ILP with melphalan with or without tumor necrosis factor (TNF) or other drugs providing valid data on clinical response, survival, or toxicity. To allocate levels of evidence and grades of recommendation the Scottish Intercollegiate Guidelines Network system was used.

Results: Twenty-two studies including 2,018 ILPs were selected with a clear predominance of observational studies (90.90%) against experimental studies (9.10%). The median complete response rate to ILP was of 58.20%, with a median overall response rate of 90.35%. ILP with melphalan yielded a median complete response rate of 46.50%, against a 68.90% median complete response rate for melphalan plus TNF ILP. The median 5-year overall-survival rate was 36.50%, with a median overall survival interval of 36.70 months. The Wieberdink IV and V regional toxicity rates were 2.00% and 0.65%, respectively.

Conclusions: ILP is effective in achieving clinical responses in patients with unresectable locally advanced melanoma of the limbs. The disease-free and overall survival rates provided by ILP are acceptable. ILP is safe, with a low incidence of severe regional and systemic toxicity.

Figure 1.

Procedure for the selection of studies included in the systematic review.

Figure 2.

Clinical effectiveness of isolated limb perfusion with melphalan and melphalan plus TNF. Median values of response are indicated by black squares, and ranges are indicated by grey bars. Abbreviations: CR, complete response; ILP, isolated limb perfusion; NR, no response; OR, overall response; PR, partial response; TNF, tumor necrosis factor.