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Isolated limb perfusion for melanoma: Effectiveness and toxicity of cisplatin compared with that of melphalan and other drugs

  • World Progress In Surgery
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Abstract

In patients with advanced or recurrent melanoma confined to a limb, hyperthermic isolated limb perfusion (ILP) with melphalan produces complete remission in 35–40% of cases and partial remission in a further 35–40%. Mild or moderate limb toxicity is usual, but severe toxic reactions in the limb sometimes occur. After preliminary reports suggested that cisplatin administered by ILP was even more effective than melphalan yet less toxic, a study was undertaken to further assess the value of hyperthermic ILP with cisplatin in the management of limb melanoma. Ten patients were treated. The procedure failed to eliminate melanoma in the limb in 5 of the 6 who received therapeutic ILPs for recurrent disease, and recurrence developed in 2 of the 4 patients who received prophylactic ILPs. Toxicity in the perfused limbs was unacceptably high, with 2 of the 10 patients having severe reactions, one necessitating amputation. We conclude from the results of this study and from a review of literature that neither cisplatin nor any other drug or drug combination so far used for ILP in melanoma patients achieves results which are clearly superior to those achieved with melphalan. Studies are currently in progress investigating double perfusion protocols, new strategies with regional hyperthermia, and the administration by ILP of biological response modifiers such as tumor necrosis factor and interferon. However, for the present, hyperthermic ILP with melphalan remains the treatment most likely to be successful in eliminating or controlling advanced or recurrent melanoma in a limb.

Résumé

Chez les patients atteints de mélanome évolué ou récidivant localisé aux membres, la perfusion sur membre isolé hyperthermique de Melphalan entraîne une rémission complète dans 35 à 40% des cas et une rémission partielle dans 35 à 40% des autres cas. Des études préliminaires ont suggéré que le cisplatin administré sur membre hyperthermique isolé était non seulement plus efficace mais aussi moins toxique que le melphalan. Une étude a donc été entreprise pour évaluer d'avantage l'efficacité des perfusions, sur membre isolé hyperthermique, de cisplatin dans le traitement des mélanomes des membres. Dix patients ont été traités. Le procédé n'a pas réussi à éradiquer le mélanome des membres chez 5 des 6 patients qui étaient traités pour une récidive de la maladie et une rechute est survenue ches 2 des 4 patients traités de façon préventive. La toxicité au niveau des membres perfusés était élevée de façon inacceptable. Deux des 10 patients ont eu des réactions sévères, un a nécessité une amputation. Il faut déduire des résultats de cette étude et à partir des données de la littérature que jusque là par perfusion sur membres isolés hyperthermiques, ni le cisplatin, ni aucune autre drogue utilisée seule ou en combinaison, n'ont démontré une efficacité clairement supérieure à celle du melphalan. Des études sont en cours, testant des protocoles de double perfusion, des stratégies nouvelles utilisant l'hyperthermie locorégionale et la perfusion sur membre isolé de modificateur de la résponse biologique comme le facteur de nécrose tumorale et l'interféron. Toutefois, à l'heure actuelle, la perfusion sur membre hyperthermique isolé de melphalan reste le traitement qui semble le plus efficace pour l'éradication ou le contrôle d'un mélanome évolué ou récidivant des membres.

Resumen

En pacientes con melanoma avanzado o recurrente confinado a una extremidad, la perfusióon hipertérmica aislada del miembro (PHAM) con melfalán resulta en remisión completa en 35–40% de los casos y remisión parcial en 35–40%. Usualmente se registra toxicidad leve o moderada por parte del miembro perfundido, aunque en ocasiones se ven reacciones severas. Con base en reportes preliminares que sugerían que el cisplatino administrado por perfusión aislada era aún más efectivo que el melfalán y menos tóxico, se emprendió un estudio para valorar el uso de la PHAM con cisplatino en el manejo de melanomas de la extremidad. Diez pacientes fueron tratados. El procedimiento falló en cuanto a eliminar el melanoma de la extremidad en 5 de 6 pacientes que recibieron PHAM terapéutica para enfermedad recurrente, y se observó recurrencia en 2 de 4 pacientes que recibieron PHAM profiláctica. La toxicidad en el miembro perfundido fue inaceptablemente alta, con 2 de 10 pacientes con reacciones severas, uno de los cuales requirió amputacion. La conclusión, después de este estudio y con base en una revisión de la literatura, es que ni el cisplatino ni ninguna otra droga o combinación de drogas hasta ahora utilizadas para perfusión aislada logra resultados claramente superiores a los obtenidos con melfalán. Actualmente hay estudios en progreso destinados a investigar protocolos de doble perfusión, nuevas estrategias con hipertermia regional y la administración por vía de perfusión aislada de agentes capaces de modificar la respuesta biológica, tales como el factor necrotizante tumoral y el interferón. Sin embargo, hasta la fecha, la PHAM con melfalán sigue siendo el tratamiento que con mayor probabilidad resulta exitoso en cuanto a eliminar o controlar un melanoma o recurrente de una extremidad.

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Thompson, J.F., Gianoutsos, M.P. Isolated limb perfusion for melanoma: Effectiveness and toxicity of cisplatin compared with that of melphalan and other drugs. World J. Surg. 16, 227–233 (1992). https://doi.org/10.1007/BF02071525

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