A phase I study dose escalation clinical study of hepatic intraarterial cisplatin, combination systemic intravenous liposomal doxorubicin in patients advanced cancer dominant liver involvement

Abstract

e13512 Background: Patients with liver metastases treated on phase I clinical trials have a median survival of 7.5 months (range, 6.0–9.5). We conducted a phase I study of hepatic arterial infusion (HAI) and intravenous (IV) chemotherapy in patients with advanced cancer and dominant liver involvement. Patients: Patients were treated with HAI cisplatin 100–200 mg/m2 intraarterially D1+ 3000 IU heparin intraarterially on D1; followed by liposomal doxorubicin 20–35 mg/m2 IV D1 every 4 wks using a conventional “3 + 3” design. Results: Thirty patients were treated (median age, 56 y; range, 15–76; 5 men, 25 women). Diagnoses were breast cancer (n=11), colorectal cancer (n= 8), ocular melanoma (n=4), and other (n=7). The median number of prior therapies was 5 (range, 1–13). Enrollment was: HAI cisplatin (mg/m2)/IV doxil (mg/m2): 100/20 (n=3); 100/25 (n=4); 100/30 (n=3); 100/35 (n=16) and 125/35 (n=4) and the maximum tolerated dose (MTD) was 100/35. Dose-limiting toxicities were Grade 4 neutropenia (2 of 4 patients), and Grade 4 thrombocytopenia (1 of 4 patients). Among 30 patients who completed cycle 1, 7 (23%) patients had no toxicity >Grade 1. Overall, 77 cycles were administered (median per patient, 4; range, 1–6). The most common toxicities were nausea/vomiting (n=23), fatigue (n=15), and constipation (n=13). Twenty-one patients were evaluable for response. Treatment resulted in a partial response (PR)(n=4) or stable disease (SD)(n=6) by RECIST in 10 (48%) patients and lasted for ≥4 months (tumor reduction by 5% to 44%). Four (19%) patients achieved a PR (tumor reduction by 38%, 42%, 44% and 51%, for 4, 4, 6, and 4 months, respectively). Of the 11 patients with breast cancer, 3 had a PR and 4 had SD. Of 4 patients with ocular melanoma, 1 had a PR and 1 SD. One patient with hepatocellular carcinoma had SD. Of 11 evaluable patients treated at the MTD, 3 (27%) had a PR and 4 (36%) had SD. Conclusions: The MTD of HAI cisplatin 100 mg/m2 and systemic liposomal doxorubicin 35 mg/m2 demonstrated antitumor activity in this patient subset. No significant financial relationships to disclose.