Fase I/II trial with melphalan for percutaneous chemosaturation (CS-PHP-Mephalan) in treating irresectable liver metastases

Malignancies of the liver are the third most important cause of cancer-related deaths in the world. This kind of cancer can be primary (origin in the liver) of secondary (metastases from another part of the body). The most common form of primary liver cancer is the hepatocellular carcinoma (HCC) en the most common form of secondary liver cancer are metastases of colorectal carcinoma (CRCLM). About 30-50% of all patients with colorectal cancer, develop liver metastases synchronous: 14.5-25%, metachronous: 14.5-25%).
Patients with liver metastases of colorectal carcinoma often have a bad prognosis, and for these patients surgical resection is the only curative option, despite the constant innovations in chemotherapy. The surgical treatment offers an acceptable morbidity, mortality and the 5-year survival is around 40-50%. Unfortunately only 20-25% of the patients with CRCLM qualify for surgery. The other patients can only be treated with chemotherapy. A part of the patients treated with chemotherapy and with initially irresectable metastases, become operable because of the response to chemotherapy. The disadvantage of systemic administration of chemotherapy in the treatment of liver metastases is that, because of systemic toxicity, the maximum tolerated dose is reached earlier than the minimum effective dose. To accomplish better results with patients with irresectable metastases confined to the liver, isolated hepatic perfusion ( IHP) has been developed. The principle of IHP is to shut the liver off of the systemic circulation by performing an operation. Subsequently the liver is flushed for an hour with a very high dose of chemotherapy, which would be toxic and lead to fatal complications when administered systemic. Then the liver is connected to the systemic circulation again. Because this procedure is associated with considerable morbidity (20%) and mortality (7%), a new procedure was developed by Delcath in which the hepatic perfusion can be performed percutaneous. Expected is that both morbidity and mortality will decrease significantly. In addition, this procedure can be performed several times.

Percutaneous chemosaturation of only the liver in patients with irresectabe colorectal metastases will be safe and effective and lead to downstaging of the tumor andprevent systemic toicity

• After 6 weeks;

• Every 3 months in the first year;

• Then once a half year;

Percutaneous isolated hepatic perfusion/chemosaturation of the liver; The principle of IHP is to shut the liver off of the systemic circulation by performing an operation. Subsequently the liver is flushed for an hour with a very high dose of chemotherapy, which would be toxic and lead to fatal complications when administered systemic. Then the liver is connected to the systemic circulation again.