Role of regional therapies compared with advances in systemic treatment for melanoma

NEW YORK — The role of intralesional injections, electrochemotherapy and regional perfusion therapies for the treatment of advanced disease, in light of advances in the systemic treatment of unresectable melanoma, was the topic of discussion at a presentation at the HemOnc Today Melanoma and Cutaneous Malignancies Meeting.

“In this review, we chose to focus on patients with regional or distant disease who are, as far as disease status at presentation, the patients that make up the minimal or smallest amount of all melanoma patients,” said Jonathan S. Zager, MD, FACS, director of regional therapies and associate professor of surgery in the Cutaneous Oncology Program at Moffitt Cancer Center in Tampa, Fla. “However, when you observe their 5-year survival rates, they represent the worst statistics for survival.”

According to Zager, the therapy a patient receives depends largely on the intended goal of the therapy: disease control — a palliative treatment in conjunction with other therapies — or a disease cure — as with limited in-transit disease that is easily treated. Professionals also must consider anticipated adverse effects of a particular therapy, the burden of disease and previous therapies that patients have already undergone.

Patient characteristics and systemic disease are also integral to the selection process, whether the patients are too ill to undergo systemic therapy or general anesthesia.

“Assuming the tumor is unresectable, and there is a high systemic burden and high regional burden, we should start with systemic treatment,” Zager said. “However, if there is a lower systemic burden or even a low-to-moderate regional burden, these are the patients you might want to start with a regional or local type treatment.”

“In the elderly patient and those with multiple medical comorbidities — who we are seeing more and more frequently presenting with metastatic melanoma — our threshold for systemic therapy might be pushed up, and even our threshold for hepatic perfusion and limb perfusions might be higher as well,” Zager said. “These are the patients we might want to consider some form of regional therapy before even entertaining systemic therapy.”

Based on recent clinical studies presented during the review, regional therapies such as electrochemotherapy, intralesional injections and isolated limb infusion were observed to be most effective for smaller volume disease. In addition, perfusions such as isolated limb infusion/isolated limb perfusion, percutaneous hepatic perfusion were found to be more effective in treating bulky disease that was regionally localized with no evidence of systemic metastases.

“Combining regional and systemic therapies for bulky disease may be best; however, which comes first really remains to be seen,” he said. “Do we start with regional therapy and then systemic therapy to control the bulk of the disease, and then put the patient on ‘maintenance’ or vice versa?

“I believe that combination therapies — an enormous gray zone in our current treatment regimen — will prove to be the best for these patients. We are going to combine local, regional and systemic therapies in one shape or form; we simply have to find the right combination for the right patient,” Zager said.

Disclosure: Dr. Zager reports no relevant financial disclosures.