Isolated limb perfusion and infusion
Isolating the blood supply of an arm or leg so that chemotherapy doses 15-20 times higher than the body could tolerate can be circulated through it, to save limbs with melanoma or sarcoma that would otherwise be amputated.
Creech and Krementz (1958) introduced isolated limb perfusion (ILP): the limb's artery and vein are cannulated and connected to an oxygenated extracorporeal circuit with a tourniquet, and hyperthermic (39-40 °C) melphalan ± TNF-α (Europe) is circulated for 60-90 minutes. Complete response rates are ~50-70% for melanoma in-transit metastases and limb salvage ~80% for locally advanced extremity sarcoma with TNF-melphalan. Isolated limb infusion (ILI, Thompson 1994) is a percutaneous, hypoxic, lower-dose variant with lower morbidity and ~30-40% complete response. Systemic immunotherapy (checkpoint inhibitors, T-VEC) has reduced ILP use in melanoma, but it remains the standard for unresectable extremity sarcoma with TNF in Europe and a salvage option after immunotherapy failure.
How it works
Vascular isolation permits regional drug concentrations far above systemic limits, with hyperthermia and TNF-α (which selectively destroys tumour vasculature) enhancing cytotoxicity and drug penetration.
- Limb salvage in otherwise unresectable sarcoma
- High complete response in melanoma in-transit disease
- Minimal systemic toxicity when leak is controlled
- Major operation; regional toxicity (Wieberdink grade)
- TNF-α not approved in the US
- Displaced in melanoma by systemic immunotherapy
The first antibiotic used as an anticancer drug (1954) and still the core of chemotherapy for Wilms tumour, rhabdomyosarcoma and gestational trophoblastic disease.
The myeloma chemotherapy that is also the standard high-dose conditioning before autologous transplant, and, delivered directly into the liver's blood supply or the eye, treats uveal melanoma metastases and retinoblastoma.
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