Novel Infusion Approach Significantly Delays Progression in Uveal Melanoma Patients With Liver Metastases

Stockholm, Sweden—Patients with liver metastases from uveal melanoma had improved survival after treatment with percutaneous hepatic perfusion (PHP), in which chemotherapy is directly infused into the liver, University of Pittsburgh investigators reported at the 2011 European Multidisciplinary Cancer Congress (EMCC).

“This is the first treatment to show a clinical benefit in patients with liver metastases from ocular melanoma,” said James Pingpank, MD, who presented the results at a press briefing.

The phase III trial randomized 93 patients to receive PHP or best alternative care (BAC), which could involve interleukin 2, ipilimumab, transcatheter arterial chemoembolization, systemic chemotherapy, or inclusion in a clinical trial.

Percutaneous hepatic perfusion saturates the liver with high doses of melphalan 3.0 mg/kg delivered via a 30-minute hepatic artery infusion, using specially designed catheters, with jugular venous return of filtered blood. Treatment was administered every 4 to 5 weeks, for up to 4 cycles.

The rationale for using melphalan is based on its history in limb perfusion, and its ability to produce high response rates with little toxicity in the liver, Pingpank explained.

“Melphalan is an effective agent for melanoma and other histologies because it gives good control, and you can dose-escalate to the level you need,” he said. “In the absence of severe liver disease it is very well tolerated.”

The adverse effects included more grade 3 and 4 neutropenia (61%), thrombocytopenia (74%), and anemia (47%), but these were transient. One patient died of hepatic failure, he said. Risk of progression reduced by 64%

The receipt of PHP significantly extended median progression-free survival (PFS), which was only 1.6 months with BAC, but reached 6.1 months with PHP, a 64%, highly significant, reduction in risk (P < .001). For patients with disease confined to the liver, median hepatic-only PFS was 1.6, versus 8.0 months (P < .0001), respectively.

“These were highly significant results in the experimental arm,” Pingpank noted.

But despite the fact that 58% of patients crossed over to the PHP arm, no survival differences were observed. Overall survival at one year was 26% with BAC and 29% with PHP, and median survival was 9.9 versus 11.4 months, respectively.

Interestingly, patients who crossed over and received “late” PHP still experienced an improvement in PFS. Median PFS in this crossover group was 6.5 months overall and 9.2 months for patients with disease confined to the liver, he reported.

Alexander Eggermont, MD, director general of the Institut de Cancerologie Gustave Roussy in Paris, commented, “One of the interesting points is that those patients who crossed over from the BAC arm of the study had PFS after ‘late’ treatment with PHP that is about the same as when PHP was given upfront. Also, in the absence of identified targets for targeted drugs in uveal melanoma, one might consider testing the role of ipilimumab following PHP.”

PHP can potentially be used for liver metastases from other cancers as well, and the investigators are obtaining encouraging results in neuroendocrine tumors, Pingpank added. The device that delivers and filters the melphalan is approved in Europe and is pending approval in the United States.