Factors predicting response to isolated limb perfusion in melanoma

The authors determined the factors that predict response to melphalan (Alkeran) delivered through isolated limb infusion (a technique to apply drugs at the tumor sites in melanoma).

Melanoma is sensitive to chemotherapy drugs, resulting in higher occurrences of adverse events. But the disease requires higher dose of chemotherapy than other types of cancer. Isolated limb infusion (ILI) is a highly sophisticated surgical technique, where high doses of chemotherapy can be given directly into the melanoma-affected limb (leg or arm). The affected limb is isolated from the blood circulation using a tight band. This way, the vital organs of the body are not exposed to the high dose of chemotherapy. This technique is particularly useful for melanoma that has spread to the adjacent lymph nodes (tiny, bean-shaped organs which help fight infections) in the skin. This is called in-transit melanoma. ILI with melphalan has been a well-established and effective treatment for  in-transit melanoma of arms and legs.

The factors that affect response to ILI are not clearly established. Burden of disease (BOD, the number and size of the tumors) could be a useful predictor of ILI response.

The authors aimed to determine if BOD could predict response to ILI with melphalan and actinomycin D (Dactinomycin) in melanoma.

Data from 160 patients with stage 3 in-transit melanoma of arms and legs were included in this study. Response to ILI was measured 3 months after the treatment. A low BOD was defined as having 10 or less tumors, the size of each tumor being less than 2 cm. A high BOD was defined as having more than 10 tumors or having single tumor greater than 2 cm. 38% of patients had low BOD (group 1) and 62% of patients had high BOD (group 2).

In group 1, patients had an overall response rate (ORR) of 73%. ORR is the extent of decrease in amount of tumors. 50% of patients had a complete disappearance of tumors (complete response-CR). In group 2, the ORR was 47% and CR was 24%.

Overall, patients with a CR at 3 months showed improved progression-free survival (time following treatment before the disease progressed) compared to others. Patients in group 1 had an average progression–free survival of 6.9 months. This was compared to 3.8 months in group 2. The average overall survival (those who were still alive following the treatment) in group 1 patients was 38.4 months. This was compared to 30.9 months in group 2.

The authors concluded that lower BOD was associated with better outcome in melanoma patients undergoing ILI. They also suggested that BOD could provide useful and predictive information in patient counseling. 

The definition of BOD for in-transit melanoma is not well established. Development of a standardized BOD score is required for future ILI therapy.