Phase I clinical trial of hepatic arterial infusion of paclitaxel in patients with advanced cancer and dominant liver involvement

The survival of patients with liver metastases from solid tumors is poor. We conducted a phase I study of hepatic arterial infusion (HAI) paclitaxel in patients with advanced cancer and predominant liver involvement. Patients were treated with HAI paclitaxel 150-275 mg/m(2) (and 15,000 IU heparin intraarterially) every 28 days. A 3 + 3 study design was used. Twenty-six patients were treated (median age, 59 years). Diagnoses were colorectal cancer (n = 10), breast cancer (n = 7), and other (n = 9). The median number of prior therapies was four (range, 0-10). The maximum tolerated dose (MTD) was HAI paclitaxel 225 mg/m(2). Dose-limiting toxicities (DLTs) included Grade 3 neuropathy (1 of 5 patients) at HAI paclitaxel 275 mg/m(2) and Grade 4 thrombocytopenia and neutropenia, and Grade 3 mucositis (1 of 4 patients) at 250 mg/m(2). None of the eight patients treated with HAI paclitaxel 225 mg/m(2) experienced a DLT. The most common toxicities were nausea and peripheral neuropathy. Of 22 patients evaluable for response, 3 (13.6%) patients had SD for a parts per thousand yen4 months (colorectal cancer, n = 1; thyroid cancer, n = 1; and hepatocellular carcinoma, n = 1; duration of response was 4 months, 7.1 months, and 22.2+ months, respectively). The MTD of HAI paclitaxel was 225 mg/m(2). This regimen was well tolerated and had antitumor activity in selected patients.