Phase III randomized trial of radiotherapy versus concurrent chemo-radiotherapy followed by adjuvant chemotherapy in patients with AJCC/UICC (1997) stage 3 and 4 nasopharyngeal cancer of the endemic variety
5500 Background: Intergroup 00–99 study for Nasopharyngeal Cancer (NPC) showed a benefit of adding chemotherapy to radiotherapy (RT). This study aimed to confirm the findings of 00–99 in patients from an endemic region. Specific objectives were to compare the rates of distant metastases, disease free (DFS) and overall survival (OS). Methods: 221 patients were randomized between 9/1997 to 5/2003. 220 are included in this analysis. 109 received radiotherapy (R) alone and 111 had chemo-radiotherapy (C). Patients were all staged by CT / MR, CXR, liver and bone imaging. All had AJCC(1997) Stage 3 or 4 disease as well as WHO Type II or III histology. All patients (C & R) received 70Gy in 7 wks using standard RT portals and techniques. Those on (C) received concurrently cisplatin (25mg/m2 D1–4) on wks 1,4 and 7 of RT and adjuvant cisplatin (20mg/m2 D1–4) and 5FU (1000mg/m2 D1–4) every 4 wks (wk 11, 15, 19) for 3 cycles following completion of RT. Results: All patients were followed up for a minimum of 6 mths. 45% had Stage III and 54% Stage IV disease. 2 patients were non-compliant in the R arm. In the C arm, 40% had dose reduction / reduced cycles of chemo during the concurrent phase; 31% did not receive any adjuvant chemotherapy; and another 27% had dose reduction / reduced or delayed cycles of chemo. 6 patients had their RT dose reduced. To date, 59 patients (37 R, 22 C) have died. Cause of death was disease-related for 51 (32 R, 19 C) . Median survival time for R was 49.9 months, but this has not been reached for those on C. 2-year DFS rates were 62% for R and 76% for C. Hazard ratio (HR) was 0.67 (95% CI: 0.42 to 1.08, p = 0.10). 2-year cumulative incidence rate for distant metastasis was 28% (95% CI 18% to 37%) for R and 14% (95% CI 7% to 21%) for C. (p = 0.034). 2-year OS rates were 77% for R and 85% for C respectively. The HR estimate was 0.54 (95% CI: 0.32 to 0.89, p = 0.02). Conclusions: This trial confirms the results of Intergroup 0099 and the results are shown to be applicable to the endemic type of NPC. This study also confirms that chemotherapy improves distant control in NPC. No significant financial relationships to disclose.