Factors predicting toxicity and response following isolated limb infusion for melanoma: An international multi-centre study

Kenyon-Smith, Timothy J.; Kroon, Hidde M.; Miura, John T.; Teras, J; Beasley, Georgia M.; Mullen, Dean; Farrow, Norma E.; Mosca, Paul J.; Lowe, Michael C.; Farley, Clara R.; Potdar, Aishwarya; Daou, Hala; Sun, James; Farma, Jeffrey M.; Henderson, Michael A.; Speakman, David; Serpell, Jonathan W.; Delman, Keith A.; Smithers, B. Mark; Barbour, Andrew P.; Coventry, Brendon J.; Tyler, Douglas S.; Zager, Jonathan S.; Thompson, John F.

doi:10.1016/j.ejso.2020.06.040

Cited by 9 publications

(8 citation statements)

References 29 publications

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“…This added effect of acidosis is caused by intensified cellular melphalan uptake, reducing the spontaneous hydrolysis rate and increased levels of nitric oxide in the tumour's micro-environment. This has been confirmed in clinical studies showing improved response rates in patients with longer tourniquet times and whose blood taken from the isolated limb had increased CO2 levels [20,29,55].…”

Section: Hypoxia and Acidosis During Isolated Limb Infusionmentioning

confidence: 53%

“…To report limb toxicity, the Wieberdink toxicity scale, historically used for HILP, has shown to be also applicable after ILI [27]. Although after ILI reported limb toxicity is at the higher end of the spectrum of that reported for HILP, long-term morbidity is less frequently observed and less severe after ILI [28,29]. Considerable erythema and/or edema with blistering (grade III toxicity) is seen in around 19% of the patients.…”

Section: Toxicity Following Isolated Limb Infusionmentioning

confidence: 99%

“…No relationship has been identified between increased limb toxicity and complete response (CR) to ILI, duration of response or survival, but a relationship was observed between limb toxicity and overall response, which likely shows the challenging balance between maximum efficacy while keeping toxicity low [29,30].…”

Section: Toxicity Following Isolated Limb Infusionmentioning

confidence: 99%

“…Various pharmacokinetic variables can predict limb toxicity after ILI. A high melphalan dosage, for instance, has been identified as a predictor of increased limb toxicity, and patients with longer ischemia times experience more severe limb toxicity [29,30]. Since uptake of melphalan is higher in muscle as opposed to fat, the skin and subcutaneous tissues of overweight patients are exposed to a relatively higher dose of melphalan [31].…”

Section: Toxicity Following Isolated Limb Infusionmentioning

confidence: 99%

“…After ILI, serious systemic side-effects, such as bone marrow depression or end-organ failure, are rarely seen and only mild postoperative nausea and vomiting is seen, which normally resolves quickly with conservative management [29,30]. The reason for the low number of patients with systemic toxicity after ILI can mainly be attributed to effective isolation placing a tourniquet around the base of the limb, while there is already low influx of chemotherapy from the isolated limb circuit to the systemic circulation due to the low flow and pressure in the isolated circuit of the to be treated limb.…”

Section: Toxicity Following Isolated Limb Infusionmentioning

confidence: 99%

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Molecular Aspects of the Isolated Limb Infusion Procedure

et al. 2021

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For decades, isolated limb infusion (ILI) and hyperthermic isolated limb perfusion (HILP) have been used to treat melanoma in-transit metastases and unresectable sarcoma confined to the limb utilizing the effect of loco-regional high-dose chemotherapy to the isolated limb. Both procedures are able to provide high response rates in patients with numerous or bulky lesions in whom other loco-regional treatments are becoming ineffective. In comparison to systemic therapies, on the other hand, ILI and HILP have the advantage of not being associated with systemic side-effects. Although in principle ILI and HILP are similar procedures, ILI is technically simpler to perform and differs from HILP in that it takes advantage of the hypoxic and acidotic environment that develops in the isolated limb, potentiating anti-tumour activity of the cytotoxic agents melphalan +/− actinomycin-D. Due to its simplicity, ILI can be used in both preclinical and clinical studies to test new cytotoxic regimens and combinations with the aim to overcome tumour resistance. In the future, administration of cytotoxic agents by ILI, in combination with systemic treatments such as BRAF/MEK/KIT inhibitors, immunotherapy (CTLA-4 blockade), and/or programmed death (PD-1) pathway inhibitors, has the potential to improve responses further by inducing increased tumour cell death while limiting the ability of the tumour to suppress the immune response.

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Section: Hypoxia and Acidosis During Isolated Limb Infusionmentioning

confidence: 53%

Section: Toxicity Following Isolated Limb Infusionmentioning

confidence: 99%

Section: Toxicity Following Isolated Limb Infusionmentioning

confidence: 99%

Section: Toxicity Following Isolated Limb Infusionmentioning

confidence: 99%

Section: Toxicity Following Isolated Limb Infusionmentioning

confidence: 99%

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Molecular Aspects of the Isolated Limb Infusion Procedure

et al. 2021

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Complications of Surgery for Cutaneous Melanoma

de Bree,

Lasithiotakis,

Michelakis

et al. 2024

Side Effects of Cancer Therapy

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Isolated hyperthermic perfusions for cutaneous melanoma in-transit metastasis of the limb and uveal melanoma metastasis to the liver

Huibers,

DePalo,

Perez

et al. 2023

Clin Exp Metastasis

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Patients with cutaneous melanoma can develop in-transit metastases (ITM), most often localized to limbs. For patients with uveal melanoma that develop metastatic disease, the overall majority develop isolated liver metastases. For these types of metastases, regional cancer therapies have evolved as effective treatments. Isolated limb perfusion (ILP), isolated limb infusion (ILI), isolated hepatic perfusion (IHP) and percutaneous hepatic perfusion (PHP) achieve a high local concentration of chemotherapy with minimal systemic exposure. This review discusses the mechanism and available literature on locoregional treatment modalities in the era of modern immunotherapy.

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Factors predicting toxicity and response following isolated limb infusion for melanoma: An international multi-centre study

Cited by 9 publications

References 29 publications

Molecular Aspects of the Isolated Limb Infusion Procedure

Molecular Aspects of the Isolated Limb Infusion Procedure

Complications of Surgery for Cutaneous Melanoma

Isolated hyperthermic perfusions for cutaneous melanoma in-transit metastasis of the limb and uveal melanoma metastasis to the liver

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