Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma.
BACKGROUND
Current practice of adding concurrent-adjuvant chemotherapy to radiotherapy (CRT) for treating advanced nasopharyngeal carcinoma is based on the Intergroup-0099 Study published in 1998. However, the outcome for the radiotherapy-alone (RT) group in that trial was substantially poorer than those in other trials, and there were no data on late toxicities. Verification of the long-term therapeutic index of this regimen is needed.


METHODS
Patients with nonkeratinizing nasopharyngeal carcinoma staged T1-4N2-3M0 were randomly assigned to RT (176 patients) or to CRT (172 patients) using cisplatin (100 mg/m(2)) every 3 weeks for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m(2)) plus fluorouracil (1000 mg per m(2) per day for 4 days) every 4 weeks for three cycles. Primary endpoints included overall failure-free rate (FFR) (the time to first failure at any site) and progression-free survival. Secondary endpoints included overall survival, locoregional FFR, distant FFR, and acute and late toxicity rates. All statistical tests were two-sided.


RESULTS
The two treatment groups were well balanced in all patient characteristics, tumor factors, and radiotherapy parameters. Adding chemotherapy statistically significantly improved the 5-year FFR (CRT vs RT: 67% vs 55%; P = .014) and 5-year progression-free survival (CRT vs RT: 62% vs 53%; P = .035). Cumulative incidence of acute toxicity increased with chemotherapy by 30% (CRT vs RT: 83% vs 53%; P < .001), but the 5-year late toxicity rate did not increase statistically significantly (CRT vs RT: 30% vs 24%; P = .30). Deaths because of disease progression were reduced statistically significantly by 14% (CRT vs RT: 38% vs 24%; P = .008), but 5-year overall survival was similar (CRT vs RT: 68% vs 64%; P = .22; hazard ratio of CRT = 0.81, 95% confidence interval = 0.58 to 1.13) because deaths due to toxicity or incidental causes increased by 7% (CRT vs RT: 1.7% vs 0, and 8.1% vs 3.4%, respectively; P = .015).


CONCLUSIONS
Adding concurrent-adjuvant chemotherapy statistically significantly reduced failure and cancer-specific deaths when compared with radiotherapy alone. Although there was no statistically significant increase in major late toxicity, increase in noncancer deaths narrowed the resultant gain in overall survival.
Lee
Anne W M
AW
Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong, China. awmlee@ha.org.hk
Tung
Stewart Y
SY
Chua
Daniel T T
DT
Ngan
Roger K C
RK
Chappell
Rick
R
Tung
Raymond
R
Siu
Lillian
L
Ng
W T
WT
Sze
W K
WK
Au
Gordon K H
GK
Law
Stephen C K
SC
O'Sullivan
Brian
B
Yau
T K
TK
Leung
T W
TW
Au
Joseph S K
JS
Sze
W M
WM
Choi
C W
CW
Fung
K K
KK
Lau
Joseph T
JT
Lau
W H
WH
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000209:etiology; D016017:Odds Ratio; D018714:Radiotherapy, Adjuvant; D013405:Suicide / Q000706:statistics & numerical data; D016896:Treatment Outcome
D002945:Cisplatin; D005472:Fluorouracil