Preliminary results of a randomized study (NPC-9902 Trial) on therapeutic gain by concurrent chemotherapy and/or accelerated fractionation for locally advanced nasopharyngeal carcinoma.
OBJECTIVE
To compare the benefit achieved by concurrent chemoradiotherapy (CRT) and/or accelerated fractionation (AF) vs. radiotherapy (RT) alone with conventional fractionation (CF) for patients with T3-4N0-1M0 nasopharyngeal carcinoma (NPC).


METHODS
All patients were irradiated with the same RT technique to > or =66 Gy at 2 Gy per fraction, conventional five fractions/week in the CF and CF+C (chemotherapy) arms, and accelerated six fractions/week in the AF and AF+C arms. The CF+C and AF+C patients were given the Intergroup 0099 regimen (concurrent cisplatin plus adjuvant cisplatin and 5-fluorouracil).


RESULTS
Between 1999 and April 2004, 189 patients were randomly assigned; the trial was terminated early because of slow accrual. The median follow-up was 2.9 years. When compared with the CF arm, significant improvement in failure-free survival (FFS) was achieved by the AF+C arm (94% vs. 70% at 3 years, p = 0.008), but both the AF arm and the CF+C arm were insignificant (p > or = 0.38). Multivariate analyses showed that CRT was a significant factor: hazard ratio (HR) = 0.52 (0.28-0.97), AF per se was insignificant: HR = 0.68 (0.37-1.25); the interaction of CRT by AF was strongly significant (p = 0.006). Both CRT arms had significant increase in acute toxicities (p < 0.005), and the AF+C arm also incurred borderline increase in late toxicities (34% vs. 14% at 3 years, p = 0.05).


CONCLUSIONS
Preliminary results suggest that concurrent chemoradiotherapy with accelerated fractionation could significantly improve tumor control when compared with conventional RT alone; further confirmation of therapeutic ratio is warranted.
Lee
Anne W M
AW
Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China. awmlee@ha.org.hk
Tung
Stewart Y
SY
Chan
Anthony T C
AT
Chappell
Rick
R
Fu
Yiu-Tong
YT
Lu
Tai-Xiang
TX
Tan
Terence
T
Chua
Daniel T T
DT
O'sullivan
Brian
B
Xu
Shirley L
SL
Pang
Ellie S Y
ES
Sze
Wai-Man
WM
Leung
To-Wai
TW
Kwan
Wing-Hong
WH
Chan
Paddy T M
PT
Liu
Xiu-Fang
XF
Tan
Eng-Huat
EH
Sham
Jonathan S T
JS
Siu
Lillian
L
Lau
Wai-Hon
WH
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D009367:Neoplasm Staging; D016896:Treatment Outcome
D002945:Cisplatin; D005472:Fluorouracil