Clinical trialPhase 3Head and neck cancers

Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma

N Engl J Med · 2019480 patients

Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, et al. N Engl J Med. 2019. 381:1124-1135

A newer report of this study has been published: Final Overall Survival Analysis of Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma: A Multicenter, Randomized Phase III Trial (2022)

Study type: Clinical trial
Study name: GP induction NPC (Zhang 2019)
Phase: Phase 3
Design: Multicentre randomised controlled parallel-group trial (1:1)
Sample size: 480 patients
Source: N Engl J Med · 2019
Trial registration: NCT01872962

In plain words

In locally advanced nasopharyngeal cancer, the main treatment is radiotherapy with cisplatin. This study showed that giving three cycles of chemotherapy with gemcitabine and cisplatin beforehand lowers the chance of the cancer coming back and helps people live longer (5-year survival about 88% vs 79%). Short-term blood and digestive side effects are more common, but late side effects did not increase.

Key results

85.3% vs 76.5%

3-year recurrence-free survival

Stratified HR 0.51; 95% CI: 0.34 to 0.77; P=0.001

94.6% vs 90.3%

3-year overall survival

HR 0.43; 95% CI: 0.24 to 0.77

87.9% vs 78.8%

5-year overall survival (final analysis, separate paper)

HR 0.51; 95% CI: 0.34 to 0.78; P=0.001 — Zhang Y et al., J Clin Oncol 2022; DOI: 10.1200/JCO.22.00327

96.7%

Completion of 3 induction cycles

Drugs in this study:Cisplatin (Platinol)Gemcitabine (Gemzar)

Dose and schedule cards

Gemcitabine + cisplatin induction, then chemoradiotherapy

Locoregionally advanced non-keratinizing nasopharyngeal cancer; in the trial: T3–4N1 or N2–3 (AJCC 7th edition), M0, KPS ≥70, creatinine clearance ≥60 mL/min, age 18 to 65 yearsCycle length: Every 21 daysOn the page “Head and neck cancers” · Nasopharyngeal cancer: locoregionally advanced and recurrent or metastatic

Locoregionally advanced non-keratinizing nasopharyngeal cancer; in the trial: T3–4N1 or N2–3 (AJCC 7th edition), M0, KPS ≥70, creatinine clearance ≥60 mL/min, age 18 to 65 years

Drug	Dose	Route	Schedule
Induction: 3 cycles
Gemcitabine	1000 mg/m²	IV	Days 1 and 8
Cisplatin	80 mg/m²	IV	Day 1
Chemoradiotherapy: 3 cycles
Cisplatin	100 mg/m²	IV	Every 3 weeks, concurrent with IMRT
Chemoradiotherapy
Intensity-modulated radiotherapy (IMRT)	Per protocol	External beam

Cycle length: Every 21 days
Duration: 3 induction cycles, then chemoradiotherapy

On the page “Head and neck cancers” · Nasopharyngeal cancer: locoregionally advanced and recurrent or metastatic

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Gemcitabine–cisplatin induction + chemoradiotherapy

Induction: gemcitabine 1000 mg/m² (1 g/m²) IV on days 1 and 8 + cisplatin 80 mg/m² IV on day 1, every 3 weeks, 3 cycles.

Then chemoradiotherapy: IMRT at 2.0 to 2.3 Gy per fraction, 5 fractions per week over 6 to 7 weeks to a total dose of 66 Gy or more to the primary tumour, with concurrent cisplatin 100 mg/m² every 3 weeks for 3 cycles (242 patients).

2Chemoradiotherapy alone

IMRT (2.0 to 2.3 Gy per fraction, 5 fractions per week over 6 to 7 weeks, total dose of 66 Gy or more to the primary tumour) with concurrent cisplatin 100 mg/m² every 3 weeks for 3 cycles (238 patients).

Source of the regimen details: Abstract of the paper and ClinicalTrials.gov NCT01872962 (IMRT details and eligibility criteria)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients aged 18 to 65 with newly diagnosed non-keratinising nasopharyngeal carcinoma, stage T3–4N1 or N2–3 (AJCC 7th edition), without distant metastasis; KPS 70 or higher; leucocytes 4000/µL or more, haemoglobin 90 g/L or more and platelets 100,000/µL or more; creatinine clearance 60 mL/min or more; no previous radiotherapy, chemotherapy or surgery (other than diagnostic). The trial was conducted in centres in China.

Endpoints

Primary endpoint: recurrence-free survival (freedom from distant or locoregional recurrence or death from any cause) in the intention-to-treat population. Secondary: overall survival, treatment adherence and safety.

Safety and side effects

Acute grade 3 or 4 adverse events: 75.7% in the induction group versus 55.7% in the standard group (more neutropenia, thrombocytopenia, anaemia, nausea and vomiting in the induction group). Late grade 3 or 4 adverse events: 9.2% versus 11.4%.

Clinical significance and place in guidelines

This trial made gemcitabine–cisplatin induction chemotherapy before chemoradiotherapy the standard of care for locoregionally advanced NPC. The NCCN guideline (Version 2.2025) considers induction chemotherapy followed by chemoradiotherapy the preferred approach for locoregionally advanced disease (T3N1–N3, T4N0–3 or T0–2N2–3) and lists GC and modified TPF as preferred induction options for EBV-related NPC.

Limitations

All patients came from endemic regions of China (non-keratinising, EBV-related NPC); in the final analysis, patients with low pretreatment EBV DNA load (less than 4000 copies/mL) may not benefit from induction; acute toxicity is higher.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.