Results of a phase II trial of gemcitabine plus doxorubicin in patients with recurrent head and neck cancers: Serum C 18-ceramide as a novel biomarker for monitoring response

Sahar A. Saddoughi, Elizabeth Garrett-Mayer, Uzair Chaudhary, Paul E. O'Brien, Larry B. Afrin, Terry A. Day, M. Boyd Gillespie, Anand K. Sharma, Christina S. Wilhoit, Robin Bostick, Can E. Senkal, Yusuf A. Hannun, Jacek Bielawski, George R. Simon, Keisuke Shirai, Besim Ogretmen

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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 C 18-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/m 2) and DOX (25 mg/m 2) 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 progressionfree 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 C 18- 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 C 18-ceramide elevation might be a novel serum biomarker of chemotherapy response.

Original languageEnglish (US)
Pages (from-to)6097-6105
Number of pages9
JournalClinical Cancer Research
Issue number18
StatePublished - Sep 15 2011

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