Phase II study of lipiodol chemoembolization with cisplatin and thiotepa with oral thalidomide for primary liver cancer and liver metastases

Abstract

4137 Background: Lipiodol chemoembolization of the liver (LCE) can result in tumor shrinkage in part by causing abrupt devascularization and hypoxia in tumor-bearing regions. Regrowth of tumors is accompanied by neovascularity. Adding an antiangiogenesis agent like thalidomide after LCE may potentially improve the antitumor response. We have previously reported on LCE using cisplatin (DDP) and thiotepa(TT) in patients (pts). with unresectable liver tumors (LT) In this pilot trial we studied the feasibility of combining LCE with DDP and TT followed by oral thalidomide in pts with LT. Methods: Pts with LT with measurable disease by CT/MRI scan had LCE. DDP 100 mg/m2 and TT 24 mg/m2 were infused via hepatic artery over 15–20 min. On days 4–59 thalidomide was given at an initial dose of 100 mg po daily with weekly increments of 100 mg to a maximum of 400 mg daily. Followup CT/MRI scans were repeated every 2–3 months. LCE was repeated every 2–3 months in stable/responding pts. Results: 18 pts were entered into the study. Diagnoses included hepatoma ( HB 14 pts), ocular melanoma (3), and adenocarcinoma (1). 6 pts could not have embolization due to portal vein occlusion and received chemotherapy only. 12 pts had LCE. 9 pts had 1 course, 2 pts had 2 courses, and 1 pt had 4 courses of therapy. 5 pts had prior chemotherapy. All 12 pts with LCE were evaluable for response and toxicity. 2 HB pts had response 18 and 12 months. 1 melanoma pt had stable disease 5 months. Toxicity was reversible, usually mild and included abdominal pain, leukopenia and thrombocytopenia, nausea, fatigue, transient transaminase elevation, skin rash, and fever. Other toxicities include ototoxicity, and peripheral neuropathy. Conclusions: LCE with cisplatin and thiotepa followed by thalidomide is feasible and toxicity manageable. Durable responses observed in HB is encouraging and accrual is continuing. No significant financial relationships to disclose.