title: Phase IB study of the combination of docetaxel, gemcitabine, and bevacizumab in patients with advanced or recurrent soft tissue sarcoma: the Axtell regimen.
abstract: BACKGROUND
  To assess the response of patients with soft tissue sarcoma (STS) to the combination of docetaxel, bevacizumab, and gemcitabine. Vascular endothelial growth factor (VEGF)-A levels and expression of VEGF-A and VEGF receptors 1 and 2 were evaluated.
  
  
  METHODS
  Thirty-eight chemotherapy-naive patients with STS were enrolled. A dose-finding study for gemcitabine from 1000, 1250, then 1500 mg/m(2) was done in nine patients (three cohorts), followed by an expansion cohort of 27 patients. Dose of docetaxel was 50 mg/m(2), bevacizumab was 5 mg/kg, and gemcitabine was 1500 mg/m(2), every 2 weeks. Serum VEGF-A was measured by enzyme-linked immunosorbent assay and tissue VEGF-A and its receptors by immunohistochemistry.
  
  
  RESULTS
  The median follow-up was 36 months. The overall response rate observed was 31.4%, with 5 complete and 6 partial responses, and 18 stable diseases lasting for a median of 6 months. There was no significant hematologic toxicity. The adverse events with the highest grade were attributed to bevacizumab. There was no correlation of VEGF pathway biomarkers with outcome.
  
  
  CONCLUSIONS
  The combination of gemcitabine, docetaxel, and bevacizumab is safe and effective in patients with STS. The most concerning adverse events were consequences of bevacizumab administration. The benefit of bevacizumab in this patient population remains unclear.
authors: Departments of Hematology/Oncology. Electronic address: claire.verschraegen@vtmednet.org.
authors: C F
authors: CF
authors: Verschraegen
authors: Departments of Hematology/Oncology.
authors: H
authors: H
authors: Arias-Pulido
authors: Departments of Hematology/Oncology.
authors: S-J
authors: SJ
authors: Lee
authors: Departments of Hematology/Oncology.
authors: S
authors: S
authors: Movva
authors: Departments of Pathology.
authors: L A
authors: LA
authors: Cerilli
authors: Departments of Radiology.
authors: S
authors: S
authors: Eberhardt
authors: Departments of Radiology.
authors: B
authors: B
authors: Schmit
authors: Departments of Surgery, The University of New Mexico Cancer Center, Albuquerque.
authors: R
authors: R
authors: Quinn
authors: Departments of Surgery, The University of New Mexico Cancer Center, Albuquerque.
authors: C Y
authors: CY
authors: Muller
authors: Departments of Hematology/Oncology.
authors: I
authors: I
authors: Rabinowitz
authors: Department of Oncology, New Mexico Cancer Care Alliance, Albuquerque, USA.
authors: M
authors: M
authors: Purdy
authors: Department of Oncology, New Mexico Cancer Care Alliance, Albuquerque, USA.
authors: D
authors: D
authors: Snyder
authors: Departments of Pathology.
authors: T
authors: T
authors: Bocklage
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016016:Proportional Hazards Models; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis; D012509:Sarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D043823:Taxoids; D042461:Vascular Endothelial Growth Factor A; D003841:Deoxycytidine; D000077143:Docetaxel; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor; D000093542:Gemcitabine