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Maximizing efficacy and minimizing toxicity in isolated limb perfusion for melanoma
J F Thompson1, D T Lai, C Ingvar
1Sydney Melanoma Unit, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
Melanoma Research
|March 1, 1994
Summary
Isolated limb perfusion (ILP) with melphalan offers effective melanoma treatment but causes toxicity. Optimizing drug concentration and using techniques like isolated limb infusion (ILI) can improve outcomes and reduce side effects.
Area of Science:
- Surgical Oncology
- Pharmacology
- Clinical Trial Methodology
Background:
- Isolated limb perfusion (ILP) with melphalan is a key treatment for recurrent melanoma.
- Complete remission rates are around 40%, with significant regional toxicity limiting its use.
- There is a need to optimize ILP efficacy and minimize associated toxicities.
Purpose of the Study:
- To investigate methods for maximizing efficacy and minimizing toxicity in isolated limb perfusion (ILP) for melanoma.
- To evaluate the relationship between melphalan concentration, temperature, and toxicity.
- To explore alternative drug choices and procedural modifications.
Main Methods:
- Analysis of 210 ILPs performed at the Sydney Melanoma Unit.
- Development of a dye dilution technique to measure perfusion circuit volume and optimize drug dosing.
- Monitoring of serum creatine phosphokinase (CPK) for early toxicity detection.
- Comparison of ILP with melphalan versus cisplatin.
- Evaluation of isolated limb infusion (ILI) as a simpler alternative.
Main Results:
- Toxicity is linked to peak melphalan concentration, area under the curve, and maximum temperature.
- A dye dilution technique allows for precise drug concentration control.
- ILP with cisplatin showed lower efficacy and higher toxicity than melphalan.
- Prophylactic ondansetron effectively managed nausea and vomiting.
- Elevated CPK (>1000 IU/l) after the first post-perfusion day indicated high risk of severe toxicity.
- Isolated limb infusion (ILI) proved effective, simpler, and repeatable.
- Excluding the foot or hand with a bandage reduced morbidity for both ILP and ILI.
Conclusions:
- Optimizing melphalan concentration and temperature during ILP can enhance efficacy and reduce toxicity.
- Serum CPK monitoring is crucial for early identification of severe toxicity risk.
- Isolated limb infusion (ILI) presents a promising, less invasive alternative for melanoma treatment.
- Procedural modifications, such as excluding extremities, can further minimize treatment-related morbidity.