title: Results of a phase II trial of gemcitabine plus doxorubicin in patients with recurrent head and neck cancers: serum C₁₈-ceramide as a novel biomarker for monitoring response.
abstract: OBJECTIVE
  Here we report a phase II clinical trial, which was designed to test a novel hypothesis that treatment with gemcitabine (GEM)/doxorubicin (DOX) would be efficacious via reconstitution of C(18)-ceramide signaling in head and neck squamous cell carcinoma (HNSCC) patients for whom first-line platinum-based therapy failed.
  
  
  METHODS
  Patients received GEM (1,000 mg/m²) and DOX (25 mg/m²) on days 1 and 8, every 21 days, until disease progression. After completion of 2 treatment cycles, patients were assessed radiographically, and serum samples were taken for sphingolipid measurements.
  
  
  RESULTS
  We enrolled 18 patients in the trial, who were evaluable for toxicity, and 17 for response. The most common toxicity was neutropenia, observed in 9 of 18 patients, and there were no major nonhematologic toxicities. Of the 17 patients, 5 patients had progressive disease (PD), 1 had complete response (CR), 3 exhibited partial response (PR), and 8 had stable disease (SD). The median progression-free survival was 1.6 months (95% CI: 1.4-4.2) with a median survival of 5.6 months (95% CI: 3.8-18.2). Remarkably, serum sphingolipid analysis revealed significant differences in patterns of C₁₈-ceramide elevation in patients with CR/PR/SD in comparison with patients with PD, indicating the reconstitution of tumor suppressor ceramide generation by GEM/DOX treatment.
  
  
  CONCLUSIONS
  Our data suggest that the GEM/DOX combination could represent an effective treatment for some patients with recurrent or metastatic HNSCC, and that serum C₁₈-ceramide elevation might be a novel serum biomarker of chemotherapy response.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Sahar A
authors.initials: SA
authors.lastname: Saddoughi
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garrett-Mayer
authors.forename: Uzair
authors.initials: U
authors.lastname: Chaudhary
authors.forename: Paul E
authors.initials: PE
authors.lastname: O'Brien
authors.forename: Larry B
authors.initials: LB
authors.lastname: Afrin
authors.forename: Terry A
authors.initials: TA
authors.lastname: Day
authors.forename: M Boyd
authors.initials: MB
authors.lastname: Gillespie
authors.forename: Anand K
authors.initials: AK
authors.lastname: Sharma
authors.forename: Christina S
authors.initials: CS
authors.lastname: Wilhoit
authors.forename: Robin
authors.initials: R
authors.lastname: Bostick
authors.forename: Can E
authors.initials: CE
authors.lastname: Senkal
authors.forename: Yusuf A
authors.initials: YA
authors.lastname: Hannun
authors.forename: Jacek
authors.initials: J
authors.lastname: Bielawski
authors.forename: George R
authors.initials: GR
authors.lastname: Simon
authors.forename: Keisuke
authors.initials: K
authors.lastname: Shirai
authors.forename: Besim
authors.initials: B
authors.lastname: Ogretmen
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D002518:Ceramides / Q000097:blood*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D012008:Recurrence; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D015415:Biomarkers; D002518:Ceramides; D003841:Deoxycytidine; D004317:Doxorubicin; D000093542:Gemcitabine