Gemcitabine Plus Cisplatin Versus Fluorouracil Plus Cisplatin as First-Line Therapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: Final Overall Survival Analysis of GEM20110714 Phase III Study

Abstract

PURPOSE GEM20110714 (ClinicalTrials.gov identifier: NCT01528618 ), the first randomized, phase III study of systemic chemotherapy in recurrent or metastatic nasopharyngeal carcinoma (NPC), reported significant progression-free survival improvement with gemcitabine plus cisplatin (GP) versus fluorouracil plus cisplatin (FP; hazard ratio, 0.55; 95% CI, 0.44 to 0.68; P < .001). Data from the final analysis of overall survival (OS) are presented here. METHODS From February 2012 to October 2015, 362 patients were randomly assigned to receive either GP (gemcitabine 1 g/m2 once daily on days 1 and 8 and cisplatin 80 mg/m2 once daily on day 1; n = 181) or FP (fluorouracil 4 g/m2 in continuous intravenous infusion over 96 hours and cisplatin 80 mg/m2 once daily on day 1; n = 181) once every 21 days. The primary end point was progression-free survival, which has been previously reported; OS was a secondary end point. RESULTS After a median follow-up time of 69.5 months with GP and 69.7 months with FP, 148 (81.8%) and 166 (91.7%) deaths occurred in the GP and FP arms, respectively. The estimated hazard ratio for OS was 0.72 (95% CI, 0.58 to 0.90; two-sided P = .004). The median OS was 22.1 months (95% CI, 19.2 to 25.0 months) with GP versus 18.6 months (95% CI, 15.4 to 21.7 months) with FP. The OS probabilities at 1, 3, and 5 years were 79.9% versus 71.8%, 31.0% versus 20.4%, and 19.2% versus 7.8%, respectively. Poststudy therapy was administered in 51.9% and 55.2% of patients in the GP and FP arms, respectively. CONCLUSION Among patients with previously untreated advanced nasopharyngeal carcinoma, those who receive GP have longer OS than those receive FP. Gemcitabine plus cisplatin should be considered a preferred front-line option for these patients.

Synergistic Antitumoral Effect of Epigenetic Inhibitors and Gemcitabine in Pancreatic Cancer Cells

“…These include compounds that target enzymes implicated in epigenetic pathways as Histone Deacetylase (HDAC), DNA methyltransferase (DNMT), Euchromatic histone lysine methyltransferase 2 (EHMT2) or G9a [ 8 ], and Sirtuins (SIRT) [ 9 ]. They could represent promising new therapeutic targets for the treatment of PDAC [ 10 ], either alone or in combination with gemcitabine [ 11 , 12 , 13 , 14 ].…”

Multimodal Treatment of Nasopharyngeal Carcinoma in Children, Adolescents and Young Adults-Extended Follow-Up of the NPC-2003-GPOH Study Cohort and Patients of the Interim Cohort

“…Except of the first prospective trial in pediatric NPC by Ghim, reported in 1998, this combination has been used in all other prospective studies of pediatric patients with nasopharyngeal carcinoma, with some studies adding a third agent such as methotrexate or docetaxel [ 3 , 4 , 17 , 18 , 26 , 27 , 33 , 34 ]. Recently, a large randomized trial in adults has shown a significant benefit for the combination of gemcitabine/cisplatin (GP) versus 5-fluoruracil/cisplatin (PF) in patients with NPC and distant metastases or refractory disease [ 35 , 36 ]. However, in adult patients with locoregionally advanced NPC, GP, and PF have so far only been compared in smaller phase II trials, without showing a clear benefit toward one regimen [ 37 , 38 ].…”

Clinical trial data of Anti–PD-1/PD-L1 therapy for recurrent or metastatic nasopharyngeal Carcinoma: A review

“…Current NCCN Head and Neck Cancer Clinical Practice Guidelines® recommend gemcitabine plus cisplatin (category 1 recommendation) as the preferred first-line systemic therapy for RM-NPC [4]. Although standard-of-care (SOC) gemcitabine plus cisplatin can provide clinical benefit in RM-NPC, it is not effective in many patients or only provides short-lived benefit (per the phase 3 GEM20110714 study: objective response rate [ORR], 64%; median progression-free survival [PFS], 7.0 months; and median overall survival [OS], 22.1 months) [8,9]. Accordingly, novel treatment options are needed to improve outcomes for patients with RM-NPC.…”