title: 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.
abstract: OBJECTIVE
  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.
authors: Phase I Program, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX 77030, USA. atsimber@mdanderson.org
authors: Apostolia M
authors: AM
authors: Tsimberidou
authors: Yang
authors: Y
authors: Ye
authors: Jennifer
authors: J
authors: Wheler
authors: Aung
authors: A
authors: Naing
authors: David
authors: D
authors: Hong
authors: Uchechi
authors: U
authors: Nwosu
authors: Kenneth R
authors: KR
authors: Hess
authors: Robert A
authors: RA
authors: Wolff
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D000093542:Gemcitabine
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000068258:Bevacizumab; D017239:Paclitaxel; D000093542:Gemcitabine
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