Gemcitabine ‘New Standard Of Care’ In Recurrent, Metastatic Nasopharyngeal Carcinoma

Phase III results support gemcitabine over fluorouracil in combination with cisplatin for the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma

medwireNews: Addition of gemcitabine to cisplatin significantly improves outcomes in patients receiving first-line therapy for recurrent or metastatic nasopharyngeal carcinoma compared with the combination of fluorouracil and cisplatin , according to research published in The Lancet.

This phase III trial enrolled 362 patients with recurrent or metastatic disease, who had not received prior systemic chemotherapy, from 22 Chinese hospitals. Participants were randomly assigned to receive either gemcitabine (1 g/m2 intravenously on days 1 and 8) or fluorouracil (4 g/m2 via continuous intravenous infusion over 96 h) – both alongside cisplatin (80 mg/m2 intravenously on day 1) – once every 3 weeks for no more than six cycles.

During a median follow-up of 19.4 months, progression-free survival, as assessed by independent review, was significantly longer for the 181 gemcitabine-treated patients than for the 181 given fluorouracil. The corresponding median times were 7.0 and 5.6 months, which equated to a significant 45% lower likelihood of disease progression or death in the gemcitabine versus fluorouracil group.

The objective response rate was also significantly higher in the gemcitabine than the fluorouracil arm, at 64% versus 42%, reports the team led by Li Zhang, from Sun Yat-sen University Cancer Center in Guangzhou, China.

And a preliminary analysis, after a median follow-up of 22 months, showed that gemcitabine also conferred an overall survival benefit relative to fluorouracil, with median times of 29.1 and 20.9 months, respectively.

The incidences of treatment-related grade 3–4 leukopenia (29 vs 9%), neutropenia (23 vs 13%) and thrombocytopenia (13 vs 2%) were significantly higher in gemcitabine-treated compared with fluorouracil-treated participants, while mucositis occurred significantly more often in the latter group (0 vs 15%).

Serious adverse events attributable to treatment were observed in 4% of patients in the gemcitabine arm and in 6% of those in the fluorouracil arm. The corresponding rates of discontinuation owing to treatment-related toxicity were 3% and 8%.

There was no treatment-related mortality in either group, and generally the toxicity profiles of both regimens were “predictable and manageable”, say the researchers.

They believe that the study findings “could establish gemcitabine plus cisplatin as the current standard first-line treatment option for this population”, one that currently has no established first-line option.

This sentiment is echoed by commentators Melvin Chua, from the National Cancer Centre Singapore, and Anthony Chan, from The Chinese University of Hong Kong, who believe that this “much anticipated” trial – the first of its kind in this patient group – “establishes gemcitabine plus cisplatin as the new standard of care in metastatic nasopharyngeal carcinoma”.

This study, together with two ongoing phase III trials assessing induction or adjuvant gemcitabine plus cisplatin in patients with high-risk nonmetastatic nasopharyngeal carcinoma, “will add to the evidence on whether gemcitabine plus cisplatin is the most effective combination for targeting systemic metastases in this cancer”, they conclude.


Zhang L, Huang Y, Hong S, et al. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial. Lancet 2016; Advance online publication 23 August. doi:

Chua MLK, Chan ATC. Gemcitabine: a game changer in nasopharyngeal carcinoma. Lancet 2016; Advance online publication 23 August. doi:

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