Adjuvant chemoradiotherapy improves survival in nasopharyngeal carcinoma

Concurrent chemoradiotherapy with cisplatin plus adjuvant cisplatin-fluorouracil extended OS compared with radiotherapy alone in high-risk patients with nasopharyngeal carcinoma, according to long-term results of the NPC-9001 phase 3 trial.

Further, initial increases in toxicity with concurrent chemoradiotherapy diminished over time, results showed.

“Our NPC-9901 trial has the largest sample size and is the only trial focusing on patients with N2-3 disease,” Anne W. M. Lee, MD, from the department of clinical oncology at University of Hong Kong Shenzhen Hospital, and colleagues wrote. “The current update is the first to report with detailed 10-year outcome data for both efficacy and late toxicities.”

The Hong Kong Nasopharyngeal Cancer Study Group initiated the NPC-9001 trial to focus on patients with T1-T4/N2-N3 disease — the patient population with the highest risk for distant failure. Previous reports from the NPC-9901 trial raised concerns about failure of concurrent-adjuvant chemoradiotherapy to improve OS due to inadequate impact on distant control, as well as increased toxicities and noncancer-related mortality.

Researchers randomly assigned 348 patients between March 1999 and January 2004 to receive radiotherapy alone (n = 176) or in combination with concurrent-adjuvant chemotherapy (n = 172). Patients assigned chemotherapy received 100 mg/m² IV cisplatin every 3 weeks for three cycles, followed by a combination of 80 mg/m² cisplatin and 1,000 mg/m² fluorouracil by 96-hour infusion every 4 weeks for three cycles.

Overall failure-free rate — defined as the time to first failure at any site — and PFS served as primary endpoints. Secondary efficacy endpoints included OS, locoregional failure-free rate and distant failure-free rate.

Four percent of patients were lost to follow-up. All survivors had a minimum follow-up of 10 years; median duration for the whole series was 10.7 years (range, 0.2-16.8).

A total of 150 patients experienced failure and 183 died of any cause.

Patients treated with chemotherapy achieved higher rates of 10-year overall failure-free survival (62% vs. 50%; P = .01), PFS (56% vs. 42%; P = .006) and cancer-specific survival (72% vs. 58%). These improvements resulted from superior locoregional control (87% vs. 74%; P = .003).

However, the impact on distant control appeared comparable between the groups (68% vs. 65%).

At 10 years, the OS rate became statistically superior for patients treated with chemotherapy (62% vs. 49%; P = .047).

Fewer patients treated with chemotherapy died of disease progression (27.3% vs. 42.6%; P = .004) without an increase in mortality directly related to chemotherapy/radiotherapy toxicity (4.1% vs. 2.8%) or incidental/unknown causes (15.1% vs. 13.1%).

Among patients who received radiotherapy alone, deaths attributed to treatment toxicities increased from 0% to 1.8% after 5 to 10 years of observation, and then increased to 3.6% after 10 years of observation.

Multivariate analysis showed the addition of chemotherapy was an independent factor for improvement of all endpoints, with the exception of distant control.

“Although the current concurrent-adjuvant chemotherapy is consistently superior to radiotherapy alone, our trial has shown that further improvements in efficacy for distant control are needed, especially for patients with stage IVA/B disease,” the researchers wrote. – by Melinda Stevens

Disclosure: The researchers report no relevant financial disclosures.