A phase I study of hepatic arterial infusion of nab-paclitaxel in combination with intravenous gemcitabine and bevacizumab for patients with advanced cancers and predominant liver metastases

作者：Tsimberidou Apostolia M^*; Ye Yang; Wheler Jennifer; Naing Aung; Hong David; Nwosu Uchechi; Hess Kenneth R; Wolff Robert A

来源：Cancer Chemotherapy and Pharmacology, 2013, 71(4): 955-963.

DOI：10.1007/s00280-013-2088-y

• Liver
• Cancer
• Metastases
• Nab-paclitaxel
• Gemcitabine
• Bevacizumab

We conducted a phase I clinical trial for patients with advanced cancer and predominant liver disease. %26lt;br%26gt;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 %26quot;3 + 3%26quot; study design was used. %26lt;br%26gt;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 a parts per thousand yen6 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). %26lt;br%26gt;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.

• 出版日期2013-4