Isolated limb perfusion for in‐transit melanoma metastases: Melphalan or TNF‐melphalan perfusion?

Abstract

Indications for treatment of melanoma in-transit metastases (ITMs) confined to the limb with isolated limb perfusion (ILP) are not well defined. This study reports the Groningen regional therapeutic perfusion experience with melphalan (M-ILP) and TNF-melphalan (TM-ILP) for ITMs, and reviews of the melanoma TNF-melphalan ILP literature. Between 1991 and 2012, 60 patients were treated with ILP. Patients with "small" ITMs received M-ILP (10-13 mg melphalan/L limb volume) and patients with "bulky" disease TM-ILP (1-4 mg TNF); 19 M-ILPs and 41 TM-ILPs were performed, 26 Stage IIIB, 31 Stage IIIB and 1 stage IV disease. Overall response after 57 ILPs was 90%; CR 27 (45%), PR 27 (45%), no response 3 (5%); after 9 M-ILPs CR 6 (32%) and 41 TM-ILPs CR 21 (51%, P = 0.124). For younger patients (<65 years) CR was 69% and for elderly patients 29% (P = 0.003). For low volume disease (<5 ITMs) CR was 75% and for high volume disease (≥5 ITMs) 41% (P = 0.038). After median follow-up of 15 months (range, 1-144) there was local recurrence or disease progression in 36 patients (60%). Positive lymph node status was associated with local progression, absence of CR and Stage IIIC disease; these were independent prognostic factors for progression to systemic disease. M-ILP is an effective regional treatment for melanoma ITMs, whereas for bulky disease TM-ILP should be the first choice. In-field progression-free survival after ILP is determined by the biological behavior of the ITMs and the patient's immune system.

A systematic review and meta‐analysis of locoregional treatments for in‐transit melanoma

“…Table summarizes the key data for each modality and presents the pooled results including the weighted ORR and meta‐analysis data. Assessed studies included: randomized controlled trials, nonrandomized phase I and II comparative and noncomparative studies, and prospective or retrospective case series (NHMRC levels II–IV evidence; Tables S2‐S9) . Only two therapies: amputation and topical imiquimod, were suitable for formal meta‐analysis ( I 2 value ≤ 40%).…”

Patients with in‐transit melanoma metastases have comparable survival outcomes following isolated limb infusion or intralesional PV‐10—A propensity score matched, single center study

“…HILP is another regional chemotherapy considered the benchmark treatment in many other Western centers. [20][21][22] While HILP is associated with higher objective response rates than those generally reported for ILI, this modality is also technically challenging and associated with more serious AEs. 23 The improved side-effect profile and reproducibility of results has led to the acceptance of ILI as a safe and effective treatment of unresectable melanoma metastases in Australia, where it remains the standard of care.…”

The Role of Regional Therapies for in-Transit Melanoma in the Era of Improved Systemic Options

“…TNF-α has been studied in combination with melphalan in regional therapy. Several retrospective studies have reported 90% or better overall response rates [ 80 , 93 , 94 ]. However, in a direct comparison, combining TNF-α with melphalan has not been proven to have an additive response.…”