CHICAGO Isolated limb infusion, a minimally invasive technique to deliver regional chemotherapy, was useful but not optimal in two melanoma studies presented at a symposium sponsored by the Society of Surgical Oncology.
In the largest isolated limb infusion (ILI) series conducted to date, involving 185 patients with advanced metastatic melanoma confined to the limb, the overall survival rate was 84% at a median follow-up of 20 months, said lead investigator Dr. Hidde Kroon, a fellow at the Sydney Melanoma Unit in Australia, where the study was performed and the technique was developed.
He reported the highest rates to date for complete response (38%) and for partial response (46%) to chemotherapy. Stable disease was seen in 10% of patients and progressive disease in 6%.
In the largest study outside Australia, however, U.S. and Taiwanese investigators concluded that isolated limb infusion was an effective way to regionally administer the cytotoxic agent melphalan, but that its efficacy fell short of isolated limb perfusion (ILP).
Sydney Melanoma Unit Experience
Dr. Kroon said that the duration of response was significantly longer in patients achieving a complete response (median 22 months) than was observed overall (median 13 months) in the Australian study.
"Response rates and duration of response after isolated limb infusion are at the lower end of those reported after conventional isolated limb perfusion," Dr. Kroon acknowledged.
"However, ILI was performed in patients with [higher stages] of disease and more comorbidities, which might explain the lower response rates, since stage of disease is a significant risk factor for responses," he said.
Most patients in the study (134, or 72%) had M.D. Anderson stage IIIA or IIIAB disease, with 3% having stage I, 8% stage II, and 16% stage IV disease.
Isolated limb infusion is essentially a low-flow ILP performed without oxygenation via percutaneous catheters. It is a minimally invasive alternative to the more labor-intensive ILP, requires no routine blood transfusion, and can be easily repeated if necessary, Dr. Kroon explained. Results have been promising, but it has not been established whether it is equally effective as isolated limb perfusion.
Patients in the Australian series were treated from 1992 to 2006 with a single isolated limb infusion of melphalan and actinomycin D for 2030 minutes under mild hyperthermic conditions. Their mean age was 74 years (range, 2993 years), and the majority (62%) were female. Disease was present in the lower limb in 172 patients, and in the upper limb in 13.
The response rate significantly decreased with increasing stage of disease, Dr. Kroon said.
Response rates were 83% in stage I patients, 53% in stage II, 43% in stage IIIA, 33% in stage IIIAB, and 23% in stage IV.
Median overall survival was 38 months, but increased significantly to 53 months in patients achieving a complete response, he reported.
In a multivariate analysis, independent prognostic factors for complete response were lower disease stage (hazard ratio, 1.69) and greater increase in CO2 level during the procedure (HR, 1.65).
The procedure was well tolerated, with only five patients developing grade 4 toxicity, and there were no amputations, said Dr. Kroon, who reported no conflicts of interest.
"We conclude that isolated limb infusion is a safe and effective alternative to conventional isolated limb perfusion to treat advanced metastatic melanoma in a limb," he said.
U.S./Taiwanese Experience
Lead investigator Dr. Georgia Beasley of the Duke University Medical Center in Durham, N.C., and associates compared outcomes after 59 ILP treatments in 54 patients against outcomes after 61 ILI treatments in 58 patients, all with in-transit malignant melanoma of the extremity.
Among 50 evaluable ILI patients, complete response was reported in 15 (30%), partial response in 7 (14%), stable disease in 5 (10%), and progressive disease in 23 (46%). The median duration of complete response was 12 months.
Isolated limb perfusion was associated with significantly better response at 3 months (complete response, 57%; partial response, 31%; and no response, 12%); however, significantly more ILP patients had grade 3 or greater toxicity, Dr. Beasley said.
There were nine compartment syndromes and two amputations among ILP patients, versus four compartment syndromes and no amputations among ILI patients.
"In our experience, limb infusion using melphalan did not appear to be as effective as limb perfusion, although the toxicity appears less," Dr. Beasley said.
The investigators noted that correcting the melphalan dose for ideal body weight appeared to minimize toxicity without altering response rates; 66% of ILI patients had their dose corrected, versus only 22% of ILP patients.