RT Journal Article
SR Electronic
T1 Results of a Phase II Trial of Gemcitabine Plus Doxorubicin in Patients with Recurrent Head and Neck Cancers: Serum C<sub>18</sub>-Ceramide as a Novel Biomarker for Monitoring Response
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 6097
OP 6105
DO 10.1158/1078-0432.CCR-11-0930
VO 17
IS 18
A1 Saddoughi, Sahar A.
A1 Garrett-Mayer, Elizabeth
A1 Chaudhary, Uzair
A1 O'Brien, Paul E.
A1 Afrin, Larry B.
A1 Day, Terry A.
A1 Gillespie, M. Boyd
A1 Sharma, Anand K.
A1 Wilhoit, Christina S.
A1 Bostick, Robin
A1 Senkal, Can E.
A1 Hannun, Yusuf A.
A1 Bielawski, Jacek
A1 Simon, George R.
A1 Shirai, Keisuke
A1 Ogretmen, Besim
YR 2011
UL http://clincancerres.aacrjournals.org/content/17/18/6097.abstract
AB Purpose: 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 C18-ceramide signaling in head and neck squamous cell carcinoma (HNSCC) patients for whom first-line platinum-based therapy failed. Experimental Design: 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. Clin Cancer Res; 17(18); 6097–105. ©2011 AACR. This article is featured in Highlights of This Issue, p. 5839