Isolated infusion offers gentler alternative for recurrent melanomas

November 1, 2007

Isolated limb infusion (ILI) offers a less-invasive alternative to limb perfusion for the treatment of recurrent melanomas, and both treatments are equally effective, according to a new study. Both treatments have side effects including swelling, redness and pain, but ILI does not require invasive surgery.

Key Points

New York - Patients with melanomas on their limbs can be spared the discomfort of traditional limb perfusion with the less-invasive alternative of isolated limb infusion (ILI), which appears to be just as effective, according to a recent study.

As many as half of recurrent melanomas occur on the limbs, and therapy that is isolated to that area spares patients the many side effects of general chemotherapy, says Mary S. Brady, M.D., an associate attending surgeon at the Memorial Sloan-Kettering Cancer Center.

But the traditional isolated limb treatment, called isolated limb perfusion (ILP), has drawbacks of its own, involving the invasive procedure of insertion of arterial and venous catheters through a surgical incision.

ILI, on the other hand, does not require surgical incision. An interventional radiologist threads the catheters in the limb and - using a tourniquet to isolate the limb - a normothermic infusion of the chemotherapy drug is circulated.

Digging deeper

In response to research out of Australia suggesting ILI's efficacy to be similar to that of ILP, Dr. Brady and her team conducted a phase 2 clinical trial on the efficacy and safety of the treatment.

The study involved 45 infusions performed on 37 patients, 32 of whom were available for response, with stage IIIB or IIIC melanoma or unresectable soft tissue sarcoma of the limb. To conduct the procedure, angiographic catheters were placed just above the knee or elbow of the extremity and general anesthesia was performed, according to the study.

The researchers then inflated a proximal tourniquet and circulated a normothermic, low-flow, hypoxic infusion of melphalan and dactinomycin through the involved limbs for 20 minutes.

In assessing tumor response at three months and morbidity at two, six and 12 weeks, the researchers found that of 32 patients, 53 percent had a significant response at three months. Among them, 25 percent had a complete response and 28 percent had a partial response. The median duration of complete response was one year.

Limb edema and erythema were common, and peak morbidity, which occurred at two weeks, was considered to be moderate in most patients, and the researchers concluded that ILI is well-tolerated.

"The response rate compares fairly favorably with response rates after isolated limb perfusion with melphalan," Dr. Brady says.

And with the various drawbacks of invasive surgery involved in isolated limb perfusion, ILI can be much easier on patients, Dr. Brady adds.

Side effects

"The side effects we see are similar but to less a degree than with isolated limb perfusion," she explains. "First, we have no surgical wound to deal with, and it's very common when you do an ILP to get wound complications, usually in the groin, and you can get flap necrosis, but we don't have those with ILI."

The common side effects seen with both ILI and ILP include swelling of the leg, redness of the leg, edema and pain, but Dr. Brady says with ILI, the symptoms typically subside after three months.

"In our trial, there was no limb loss or compartment syndrome, and patients were generally back to baseline at three months after treatment in terms of the function and appearance of their limb."

ILI is much easier than ILP from both a patient and a clinical standpoint. The latter, which is only performed at a few centers in the United States, requires having access to a cardiopulmonary bypass team, and the perfusion takes four to six hours in the operating room.

ILI, meanwhile, is much less resource-intensive, Dr. Brady explains.