Noteworthy Success with Gemcitabine and Cisplatin for Nasopharyngeal Cancer

Platinum -based chemotherapy with concurrent radiotherapy (chemoradiotherapy) is standard treatment for locally/regionally advanced nasopharyngeal (upper throat) cancers . Adding gemcitabine to cisplatin —called induction therapy —had previously improved disease outcomes in phase-2 clinical trials, so a phase-3 trial was conducted. Results were presented on the first day of the congress that began on May 31, 2019, in Chicago, United States, organized by the American Society of Clinical Oncology as its 2019 Congress (ASCO 2019), and simultaneously published in NEJM .

A tumor in the nasopharyngeal region is illustrated below:

Nasopharyngeal cancers affected an estimated 130.000 patients worldwide in 2018, with the highest rates in regions of southern China, Southeast Asia and North Africa.

Among patients with nasopharyngeal cancer, more than 70%have locally/regionally advanced disease at diagnosis. In this group with an expected unfavorable disease course, radiotherapy and platinum-based chemotherapy that sensitizes the tumor to radiotherapy form the foundation of treatment.

Study Details

In this multicenter, randomized, controlled phase-3 clinical trial, patients were divided into two arms in a 1-to-1 ratio:

• the experimental arm received gemcitabine and cisplatin chemotherapy in addition to chemoradiotherapy,
• while the control arm received only standard chemoradiotherapy.

In the experimental arm, 3 cycles every 21 days of induction therapy (gemcitabine 1000 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2 on day 1) were followed by chemoradiotherapy (3 cycles of cisplatin 100 mg/m2 every 3 weeks, concurrent with radiotherapy). The selected radiation technique was IMRT (intensity-modulated radiotherapy). The control arm received chemoradiotherapy alone.

The study’s primary endpoint, recurrence-free survival or death from any cause, was specified. Secondary endpoints were overall survival, treatment adherence and safety (side effects).

Results

• A total of 480 patients were enrolled: 242 in the induction arm and 238 in the control arm. 
• During a median follow-up of 42.7 months, 3-year recurrence-free survival was 85.3% in the induction group versus 76.5% in the control group, a statistically significant difference (hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P=0.001). 
• In the experimental arm, 96.7% of patients completed induction therapy. 
• Early-onset severe (grade 3 and 4) side effects occurred in 75.7% of the induction arm versus 55.7% of the standard-treatment arm. 
• In the induction arm, neutropenia, thrombocytopenia, anemia and nausea and vomiting were more common.
• Late-onset severe (grade 3 and 4) side effects occurred in 9.2% of the induction chemotherapy arm versus 11.4% of the standard chemoradiotherapy arm.

Commentary

Presented on the first day of ASCO 2019, this study offers data that will change clinical oncology practice. Adding induction chemotherapy to standard chemoradiotherapy for regionally advanced nasopharyngeal cancer significantly improved recurrence-free and overall survival compared with chemoradiotherapy alone. This was achieved without a substantial additional risk of serious side effects, and most patients completed treatment.