title: Phase II study of doxorubicin and bevacizumab for patients with metastatic soft-tissue sarcomas.
abstract: OBJECTIVE
  To evaluate the antitumor activity and tolerability of bevacizumab and doxorubicin in patients with metastatic soft-tissue sarcoma (STS).
  
  
  METHODS
  Patients may have had up to one nonanthracycline line of therapy. Seventeen patients with metastatic STS were treated with doxorubicin at 75 mg/m2 intravenous (IV) push followed by bevacizumab 15 mg/kg IV every 3 weeks. Dexrazoxane was started for total doxorubicin dose exceeding 300 mg/m2.
  
  
  RESULTS
  A total of 85 cycles of doxorubicin/bevacizumab were administered, median four cycles (range, one to 11), with three patients receiving one to four cycles of bevacizumab maintenance after reaching 600 mg/m2 doxorubicin. All 17 patients were assessable for response. Two partial responses (12%, 95% CI = 1% to 36%) were observed, lasting seven and 12 cycles of therapy. Eleven patients (65%) had stable disease for four cycles or more. Six patients developed cardiac toxicity grade 2 or greater, with four patients grade 2 (cumulative doxorubicin 75, 150, 300, 300 mg/m2, respectively), one grade 3 (total doxorubicin 591 mg/m2), and one grade 4 (total doxorubicin 420 mg/m2). One patient with extensive lung disease died of recurrent bilateral pneumothoraces, possibly treatment-related.
  
  
  CONCLUSIONS
  The 12% response rate for these patients was no greater than that observed for single-agent doxorubicin. However, the 65% of patients with stable disease lasting four cycles or longer suggests further study is warranted in STSs. The observed cardiac toxicity, despite close monitoring and standard use of dexrazoxane, obliges a change in the dose and/or schedule in future studies of this combination.
authors.affiliation: Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. dadamod@mskcc.org
authors.forename: David R
authors.initials: DR
authors.lastname: D'Adamo
authors.forename: Sibyl E
authors.initials: SE
authors.lastname: Anderson
authors.forename: Karen
authors.initials: K
authors.lastname: Albritton
authors.forename: Jennifer
authors.initials: J
authors.lastname: Yamada
authors.forename: Elyn
authors.initials: E
authors.lastname: Riedel
authors.forename: Kelly
authors.initials: K
authors.lastname: Scheu
authors.forename: Gary K
authors.initials: GK
authors.lastname: Schwartz
authors.forename: Helen
authors.initials: H
authors.lastname: Chen
authors.forename: Robert G
authors.initials: RG
authors.lastname: Maki
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D004317:Doxorubicin