A phase I/II study of continuous intra-arterial chemotherapy using an implantable reservoir for the treatment of liver metastases from breast cancer:A Japan Clinical Oncology Group (JCOG) Study 9113

Background: Liver metastasis from breast cancer has a poor prognosis. While there are some reports of good response rates of hepatic metastasis from b reast cancer by hepatic intra-arterial infusion chemotherapy, no phase I st udy including pharmacokinetic analysis has been reported. We performed a ph ase I/II study of intra-arterial infusion chemotherapy using adriamycin and 5-fluorouracil to find the maximum tolerated dose and response rate in pat ients with advanced or recurrent breast cancer. Methods: A hepatic arterial catheter with an access port was inserted into the proper hepatic artery. Patients received 30 mg/m(2) adriamycin on days 1 and 8 and 100 mg/m(2) 5-fluorouracil at level 1, 200 mg/m(2) at level 2, 300 mg/m(2) at level 3 and 400 mg/m(2) at level 4 continuously from day 1 t hrough day 14 every 28 days. At least two cycles were required before evalu ation. Twenty-eight patients were entered into this study and 26 patients w ere evaluable. Seventeen patients had hepatic metastasis only, although nin e patients had additional metastasis to other sites. Results: Dose-limiting toxicity of thrombocytopenia and neurotoxicity occur red at level 4. Leukocytopenia (ECOG grade 3-4) was observed in five (19%), thrombocytopenia in three (12%) and anemia in two (8%) patients. There wer e 11 catheter-related complications which were not dose dependent. Seven ou t of 13 evaluable patients (54%) responded at level 3. The median duration of response was 5.8 months (range, 1-23+) and median survival was 25.3 mont hs (range, 6.2-54.7+). Conclusion: Hepatic arterial infusion therapy appears to be safe and effect ive but catheter-related complications must be overcome before starting a p hase III trial.