The evidence supporting this protocol is provided by a phase 3 multicentre randomised trial involving 362 patients, comparing cisplatin plus gemcitabine with cisplatin plus fluorouracil in patients with recurrent or metastatic nasopharyngeal cancer in the first-line setting.r
Between February 2012 and October 2015, 181 patients were randomised to receive cisplatin (80 mg/m2 IV on day 1) and gemcitabine (1000 mg/m2 IV on days 1 and 8) and 181 patients were randomised to receive cisplatin (80 mg/m2 IV on day 1) plus fluorouracil (4000 mg/m2 via continuous IV infusion over 96 hours) every 3 weeks for a maximum of six cycles.
The primary end point was progression-free survival and secondary end points were objective response rate, disease control rate, safety profiles, and overall survival. Progression-free survival, objective response rate, and overall survival were statistically superior in the cisplatin plus gemcitabine group. Survival data is only early.
Efficacy
After a median follow up of 19.4 months, the progression-free survival was 7.0 months in cisplatin plus gemcitabine vs 5.6 months in cisplatin plus fluorouracil group (HR=0.55; CI 95% 0.44 to 0.68 ; p<0.0001). The median follow-up for overall survival was 22.0 months, with median overall survival 29.1 months for cisplatin plus gemcitabine vs 20.9 months for cisplatin plus fluorouracil group (HR=0.62; CI 95% 0.45-0.84; p=0.0025).r
Evaluation of treatmentr |
Cisplatin plus gemcitabine
(%)
|
Cisplatin plus fluorouracil
(%)
|
p value |
Overall response rate (ORR) |
64 |
42 |
<0.0001 |
Disease control rate (DCR) |
90 |
86 |
NS |
Progression-free survival (months) |
7.0 |
5.6 |
<0.0001 |
Overall survival (months) |
29 |
20.9 |
0.0025 |
Kaplan-Meier curves (A) Progression-free survival (B) Overall survivalr
© Lancet 2016
Toxicityr
The main grade 3/4 toxicities of the various treatments are summarised in the table below.
Toxicityr |
Gemcitabine plus cisplatin
(%) |
Fluorouracil plus cisplatin
(%) |
P for difference |
Grade 3 |
Grade 4 |
Grade 3 |
Grade 4 |
Neutropenia |
21 |
2 |
11 |
2 |
0.0251 |
Thrombocytopaenia |
11 |
2 |
1 |
1 |
0.0007 |
Anaemia |
3 |
1 |
1 |
0 |
0.125 |
Mucosal inflammation |
0 |
0 |
13 |
2 |
<0.0001 |
Fatigue |
1 |
0 |
1 |
1 |
0.548 |
Nausea |
1 |
1 |
2 |
1 |
0 |