High-Dose Melphalan Granted Orphan Drug Status for Neuroendocrine Liver Metastases

Yael Waknine

June 10, 2009

June 10, 2009 — The FDA this month approved orphan drug designation for melphalan infusion (Delcath Systems, Inc) in the treatment of patients with neuroendocrine tumors metastatic to the liver.

The product uses a proprietary delivery system (percutaneous hepatic perfusion [PHP]) to deliver ultrahigh doses of melphalan to the liver while preventing access to the bloodstream, thereby potentially circumventing most adverse events.

According to information on the company Web site, benefits of the procedure include that:

  • PHP is minimally invasive — it uses a series of catheters and extracorporeal filters to infuse liver tumors with minimal systemic exposure.

  • PHP provides higher dosing — it allows infusion doses exceeding those of systemic or intraarterial administration.

  • PHP is a repeatable procedure — in contrast with isolated hepatic perfusion, which can only be performed once, PHP can be repeated several times. Clinical trial patients usually receive treatment at 4-week intervals to a maximum of 10 treatments.

  • PHP offers decreased toxicity — filtration of hepatic venous effluent can reduce systemic exposure to chemotherapy by 80% to 90% compared with hepatic artery infusion alone.

According to a company news release, investigators are currently recruiting patients with pancreatic islet-cell and carcinoid tumors in a melphalan/PHP phase 2 trial at the National Cancer Institute in Bethesda, Maryland.

Melphalan previously was granted orphan drug status in the treatment of metastatic cutaneous melanoma and metastatic ocular melanoma. It is currently under investigation for primary and metastatic cancers of the liver.

Melphalan tablets (Alkeran, GlaxoSmithKline) are approved by the FDA for the palliative treatment of multiple myeloma and for the palliation of nonresectable epithelial carcinoma of the ovary. Melphalan injection may be used in patients with multiple myeloma for whom oral therapy is not appropriate.


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