Chemoembolization of primary and metastatic liver tumors

Over the last 5 years, we have conducted 4 Phase 1-11 trials of chemoembolization for patients with unresectable primary and metastatic liver tumors. The entry criteria for these studies were KPS > 60 %, liver predominant tumor, no gross ascites, patent portal vein and a bilirubin < 7 mg/dl. All patients were treated until the cessation of blood flow was achieved and those patients who responded were retreated at the time of hepatic progression. In one study, 84 patients with hepatoma were chemoembolized with a mixture of gelfoam powder, contrast media, and three chemotherapeutic agents (doxorubicin, mitomycin-C, cisplatin). The median % liver replacement was 50 % (range 10-95 %) and 42/84 patients (50 %) were HBSAG +. There were 19 PR's (23 %) and 23 MR's (27 %). In addition, 48/84 (57 %) patients had liquefaction necrosis of their tumor on CT or MRI scan and 76 % had a > 50 % reduction in AFP. The median survival from chemoembolization was 8.7 months. In another study, 72 patients with liver-predominant metastases from a variety of primaries were chemoembolized with the same regimen. Partial responses were observed in 3/9 patients with metastatic breast cancer, 3/14 patients with metastatic leiomyosarcoma, 2/6 patients with metastatic ocular melanoma and 8/17 having metastatic carcinoid or islet cell tumors. Two chemoembolization studies were conducted for patients with metastatic colorectal cancer to the liver. In the first, 26 patients were chemoembolized with Angiostat collagen and mitomycin-C. Three PR's (12 %) and four MR's were observed. In the second study, 12 patients with colorectal cancer metastatic to the liver were chemoembolized with Gelfoam and escalating doses of FUDR. No objective responses were seen at doses up to 400mg; dose escalation continues. The common toxicities observed in all of these studies were pain, nausea and vomiting, hepatic transaminasemia and fever. Chemoembolization produced encouraging responses in patients with heptoma and liver metastases from ocular melanoma, carcinoid, islet cell tumors, breast cancer, and leiomyosarcoma, but appears to have limited activity in the treatment of colorectal cancer metastatic to the liver. The exact role of chemoembolization relative to other therapies, the optimal particle plus drug combinations, the role of lipiodol, and when to repeat treatment remain to be determined.