Related Experiment Videos
Systemic toxicity after isolated limb perfusion with melphalan for melanoma
E J Sonneveld1, B C Vrouenraets, B N van Geel
1Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Abstract:
Systemic exposure to melphalan is minimized during isolated limb perfusion (ILP) by isolating a limb from the rest of the body. Consequently, there should be no toxicity to vital organs. At present systemic toxicity after ILP has not been studied in detail. Therefore, the incidence, nature and risk factors of systemic toxicity was retrospectively studied in 368 patients who underwent a single ILP with melphalan between 1978-1990. Some form of systemic toxicity occurred in 98 patients (27%). Nausea and vomiting after the 1st post-ILP day was seen in 73 patients (20%), and in seven (2%) treatment was required. Bone marrow depression was encountered in seven patients (2%): WHO grade II in five, and grade III in two. Miscellaneous systemic side-effects, including fever and minimal scalp hair loss, occurred in 19 patients (5%). Leakage from the isolated circuit to the systemic circulation was measured with radioactive tracers. Mean cumulative leakage during ILP was 0.9%. Systemic toxicity was not increased in patients with leakage greater than 1% or 5%. Female sex was associated with an increased incidence of systemic toxicity (P<0.05). Age over 60 years (P<0.05) and more severe acute regional toxicity (P<0.05) were correlated with nausea and vomiting. The miscellaneous systemic side-effects were more frequently encountered in women than in men (P<0.05). In conclusion, systemic toxicity was rarely severe, with nausea and vomiting being the most frequently encountered side-effects. Age over 60 years, female sex and more severe acute regional toxic reactions were correlated with an increased incidence of systemic side-effects. Systemic leakage during ILP was not associated with toxicity, probably due to the low incidence of significant leakage.
Insights
Systemic toxicity after isolated limb perfusion (ILP) with melphalan is uncommon and rarely severe. Risk factors for side effects include female sex, age over 60, and regional toxicity, but not systemic leakage.
Area of Science:
- Oncology
- Pharmacology
- Clinical Medicine
Background:
- Isolated limb perfusion (ILP) with melphalan aims to minimize systemic exposure.
- Systemic toxicity following ILP has not been extensively studied.
- Understanding toxicity is crucial for patient safety and treatment protocols.
Purpose of the Study:
- To retrospectively investigate the incidence, nature, and risk factors of systemic toxicity after melphalan ILP.
- To identify patient characteristics and procedural factors associated with systemic side effects.
Main Methods:
- Retrospective analysis of 368 patients undergoing single melphalan ILP (1978-1990).
- Assessment of systemic toxicity, including nausea, vomiting, bone marrow depression, and miscellaneous effects.
- Measurement of systemic leakage using radioactive tracers and correlation with toxicity.
- Statistical analysis to identify risk factors (age, sex, regional toxicity, leakage).
Main Results:
- 27% of patients experienced some systemic toxicity.
- Nausea and vomiting occurred in 20% (requiring treatment in 2%).
- Bone marrow depression (WHO grade II/III) occurred in 2%.
- Miscellaneous side effects (fever, hair loss) occurred in 5%.
- Systemic leakage averaged 0.9% and did not correlate with increased toxicity.
- Female sex, age >60, and severe regional toxicity were associated with increased systemic side effects.
Conclusions:
- Systemic toxicity from melphalan ILP is generally mild and infrequent.
- Nausea and vomiting are the most common side effects.
- Patient factors like age and sex, along with regional toxicity severity, are key risk factors.
- Low systemic leakage during ILP does not appear to increase toxicity risk.