Systemic Effects of Hyperthermic Isolated Lower Limb Perfusion with Carboplatin and Interferon‐β

Abstract

The changes in systemic circulation during hyperthermic isolated lower limb perfusion with carboplatin and interferon-beta were investigated in 19 patients with malignant melanoma. The cardiac output (CO) increased significantly (p < 0.01) from 3.81 +/- 0.22 L/min before the procedure to 5.30 +/- 0.49 L/min 1 h after hyperthermic perfusion. The double product (mean arterial pressure x heart rate) also increased significantly (p < 0.01) from 5,145 +/- 372 mm Hg/min to 6,760 +/- 486 mm Hg/min. In some patients, it increased to more than twice the control value. These changes were accompanied by an increase in body temperature, presumably caused by the systemic leakage of both warmed blood and interferon-beta. Blood chemistry data demonstrated no significant changes in the liver or renal function. However, the serum CPK level increased markedly on the first postoperative day, and persisted for 1 week, thus suggesting that some muscle damage occurred during the procedure. There was no operative death or severe complications. From these data, we concluded that hyperthermic isolated limb perfusion with interferon-beta is a relatively safe therapeutic method for malignant melanoma of the extremities. However, care should be taken in patients with ischemic heart disease who may suffer a heart attack due to the rapid increase in cardiac work during the procedure.

Efficacy of superficial and deep regional hyperthermia combined with systemic chemotherapy and radiotherapy in metastatic melanoma

“…Carboplatin concentrations in melanoma metastases have been measured by microdialysis and have shown to achieve 50 – 60 % of serum levels [22]. In hyperthermic isolated lower limb perfusion, carboplatin and interferon‐β have been used with local recurrence in only 2 out of 19 patients [16]. In systemic treatment, carboplatin has been used as single agent with remission rates between 16 and 19 %, as well as in combination with cisplatin with remission rate of 26 % [23, 24, 25].…”

“…Whole body hyperthermia, induced either by reinfusion of extracorporally heated blood or by an Aquatherm radiant heat device, has been used in the treatment of refractory soft tissue sarcomas in several protocols [6]. A common type of regional hyperthermia, used often in melanoma patients is hyperthermic isolated limb perfusion with a variety of cytotoxic agents [15, 16]. Local hyperthermia, like deep regional and superficial hyperthermia, is produced by using arrays of multiple applicators or single microwave or ultrasound applicators [6].…”