Purpose: We conducted a phase I clinical trial for patients with advanced cancer and predominant liver disease.
Methods: Patients were treated with HAI nab-paclitaxel (120-210 mg/m(2); day 1); intravenous bevacizumab (10 mg/kg; day 1); and intravenous gemcitabine (600-800 mg/m(2); days 1 and 8). A conventional "3 + 3" study design was used.
Results: Fifty patients with advanced cancer and predominant liver metastases were treated (median age, 58 years; 27 women, 23 men; median number of prior therapies, 3 [range 0-12]). The most common cancers were breast (n = 9) and pancreatic (n = 9). Overall, 264 cycles were administered (median/patient, 4; range 1-17). No dose-limiting toxicities were noted during the escalation phase. On dose level 4, 3 patients were unable to receive gemcitabine on day 8 because of severe thrombocytopenia. Dose level 3 was selected as the maximum-tolerated dose (HAI nab-paclitaxel 180 mg/m(2) and intravenous gemcitabine 800 mg/m(2) and bevacizumab 10 mg/kg); 32 patients were treated in the expansion phase. The most common treatment-related toxicities were thrombocytopenia (n = 17), neutropenia (n = 10), and fatigue (n = 12). Of 46 patients evaluable for response, 9 (20 %) had a partial response (PR) and 9 (20 %) had stable disease for ≥6 months. The median overall survival duration was 7.0 months (95 % CI: 4, 22 months), and the median progression-free survival duration was 4.2 months (95 % CI: 2.7, 8.6 months).
Conclusions: HAI nab-paclitaxel in combination with gemcitabine and bevacizumab was well tolerated and had antitumor activity in selected patients with advanced cancer and liver metastases.