Toxicity of hyperthermic isolated limb perfusion with cisplatin for recurrent melanoma of the lower extremity after previous perfusion treatment

Abstract

Background. Hyperthermic isolated limb perfusion (HILP) has been shown to be effective for locoregional metastases or local recurrent disease. Locoregional recurrences after previous HILP is an unsolved problem. Methods. HILP with cisplatin, 20–30 mg/l perfused limb volume, was performed in seven patients with recurrent melanoma (five with Stage IIIA and two with Stage IIIAB) after previous HILP with melphalan with or without dactinomycin. A cisplatin perfusion without local excision was performed in four patients; this treatment resulted in two complete responses and one partial response. In three patients, a cisplatin perfusion was performed with local excision of the in‐transit metastases. Results. During a median follow‐up of 20 months (range, 10–25 months), in five (83%) patients the tumor recurred locally after a median period of 5 months (range, 3–11 months). No systemic toxicity was observed. Local toxicity consisted of postperfusion edema and neurotoxicity in all patients. The edema resolved within 2 weeks, which was in contrast to persistent neurotoxicity. A severe motor‐sensory neuropathy was observed in three (43%) patients and mild sensory neuropathy in four (57%) patients. Conclusions. The severe neurotoxicity and the high local recurrence rate do not justify the use of HILP with cisplatin for recurrent melanoma after previous HILP with melphalan with or without dactinomycin.

Efficacy of repeat isolated limb infusion with melphalan and actinomycin D for recurrent melanoma

“…In the past, some studies have investigated the use of other cytotoxic drugs, such as cisplatin and fotemustine, to treat recurrent or persistent melanoma after a previous ILI or ILP. [26][27][28] Results of these studies showed no improvement compared with melphalan-based procedures, and the toxicity and morbidity of these alternative cytotoxic regimens were unacceptably high. Toxicity after ILI and ILP has been shown to be similar.…”

Isolated limb perfusion with melphalan for melanoma

“…The addition of tumor necrosis factor alpha has been reported to be beneficial in patients with bulky tumor nodules; perfusion with this drug combination is discussed in a separate article in this seminar edition. The use of other agents has been investigated, including cisplatin, vindesine, DTIC, fotemustine, interleukin-2, and lymphokine-activated killer cells, but only actinomycin (in combination with melphalan) has been widely used [4][5][6][7][8][9][10][11][12].…”

Isolated limb perfusion for extremity soft-tissue sarcomas, in-transit metastases, and other unresectable tumors: Credits, debits, and future perspectives

“…When comparable results were obtained, this was often at the cost of increased regional toxicity [26][27][28]. Thus, melphalan remains the standard cytostatic drug for melanoma to be used in ILP.…”