Delcath liver isolation device shows promise in cancer trial

The chemotherapy agent melphalan was administered to 24 patients using the PHP delivery system in a Phase II clinical trial.

Only 19 of those receiving the drug could be fully evaluated, with a significant tumour reduction reported for two patients and a partial tumour reaction in a further 13 people.

This gave an objective tumour response of 79 per cent and Delcath has said it now plans to submit a new trial protocol to the US Food and Drug Administration (FDA) for the use of PHP as a first-line treatment for liver cancer.

Dr James Pingpank Jr, MD of the Surgery Branch of the National Cancer Institute in Bethesda, said: " The Delcath PHP System is unique in its ability to isolate then repeatedly treat unresectable liver tumours with high doses of anti-cancer agents such as melphalan. "

This study shows that PHP with melphalan has efficacy in patients with diffuse metastatic neuroendocrine tumors of the liver that are too extensive for resection, ablation, or embolization.

Responses to therapy tend to be durable, and repeat therapy is effective on progression or recurrence of disease. "

Speaking to in-PharmaTechnologist.com, CEO and president of Delcath Systems Richard Taney discussed the benefits of the PHP system.

He said: " As long as the patient is able to safely receive anesthesia or is healthy enough to receive systemic chemotherapy the procedure would not be too stressful for them. "

Most patients in our trials have been heavily pre-treated with a variety of regionalized and systemic therapies and had continued to show progression of disease prior to coming on trial ."

The PHP delivery system isolates the liver from the rest of the body, allowing high drug doses to be administered, without the body suffering from the toxic effects of the chemotherapeutic agent.

This is achieved through the use of a double balloon catheter to block the inferior vena cava which normally drains the liver.

By doing this hepatic venous outflow is isolated and the blood diverted through a filtration system outside the body which removes the chemotherapeutic agent before returning the blood.

This reduces the body's exposure to the toxic effects of the chemotherapy by 80 to 90 per cent compared to hepatic artery infusion alone.

In doing so the PHP system seeks to protect the liver and the rest of the body from the harmful effects of the chemotherapeutic agents.

Taney said: " We have not seen toxicities to the healthy liver tissue with this procedure as blood flow to the liver is never stopped during this procedure and this is the case despite the high doses of melphalan. "

In the prior surgical isolation procedures in the 1990s they were using doses of melphalan that were three times higher than the normal systemic dose, they were seeing high levels of liver cell toxicities and the surgical procedure could be performed only once.

" The Delcath System administers doses seven times higher than the approved systemic dose, with no liver toxicities and is repeatable (has been done 10 times to a single patient).

"

Melphalan has been delivered at a maximum dose of 3.5mg/kg and even then no liver toxicities were detected.

The dose is currently limited as the filtration system can remove only 80 to 85 per cent of the chemotherapeutic agent but will probably increase in the future as Delcath is currently investing heavily in filtration technology, according to Taney.

This improved filtration technology should prove beneficial for melphalan delivery, as well as the other agents Delcath envisage using PHP for.

So far two mainstay cancer drugs 5-FU and doxorubicin have also been tested on humans, with other agents in the pipeline.