TY - JOUR
T1 - Results of a phase II trial of gemcitabine plus doxorubicin in patients with recurrent head and neck cancers
T2 - Serum C 18-ceramide as a novel biomarker for monitoring response
AU - Saddoughi, Sahar A.
AU - Garrett-Mayer, Elizabeth
AU - Chaudhary, Uzair
AU - O'Brien, Paul E.
AU - Afrin, Larry B.
AU - Day, Terry A.
AU - Gillespie, M. Boyd
AU - Sharma, Anand K.
AU - Wilhoit, Christina S.
AU - Bostick, Robin
AU - Senkal, Can E.
AU - Hannun, Yusuf A.
AU - Bielawski, Jacek
AU - Simon, George R.
AU - Shirai, Keisuke
AU - Ogretmen, Besim
PY - 2011/9/15
Y1 - 2011/9/15
N2 - 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.
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 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.
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U2 - 10.1158/1078-0432.CCR-11-0930
DO - 10.1158/1078-0432.CCR-11-0930
M3 - Article
C2 - 21791630
AN - SCOPUS:80052853172
SN - 1078-0432
VL - 17
SP - 6097
EP - 6105
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 18
ER -