Phase II study of neoadjuvant carboplatin and paclitaxel followed by radiotherapy and concurrent cisplatin in patients with locoregionally advanced nasopharyngeal carcinoma: therapeutic monitoring with plasma Epstein-Barr virus DNA.
OBJECTIVE
To assess the efficacy of neoadjuvant paclitaxel and carboplatin (TC) followed by concurrent cisplatin and radiotherapy (RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to monitor treatment response with plasma Epstein-Barr virus (EBV) DNA.


METHODS
Thirty-one patients with International Union Against Cancer stages III and IV undifferentiated NPC had two cycles of paclitaxel (70 mg/m2 on days 1, 8, and 15) and carboplatin (area under the curve 6 mg/mL/min on day 1) on a 3-weekly cycle, followed by 6 to 8 weeks of cisplatin (40 mg/m2 weekly) and RT at 66 Gy in 2-Gy fractions. Plasma EBV DNA was measured serially using the real-time quantitative polymerase chain reaction method. Results All patients completed planned treatment. Response to neoadjuvant TC was as follows: 12 patients (39%) achieved partial response (PR) and 18 achieved (58%) complete response (CR) in regional nodes; five patients (16%) achieved PR and no patients achieved CR in nasopharynx. At 6 weeks after RT, one patient (3%) achieved PR and 30 patients (97%) achieved CR in regional nodes, and 31 patients (100%) achieved CR in nasopharynx; 29 patients (93%) had EBV DNA level of less than 500 copies/mL. Neoadjuvant TC was well tolerated, and the most common acute toxicity of cisplatin plus RT was grade 3 mucositis (55%). At median follow-up of 33.7 months (range, 7 to 39.3 months), six distant and three locoregional failures occurred. Plasma EBV DNA level increased significantly in eight of nine patients who experienced treatment failure but did not increase in those who did not. The 2-year overall and progression-free survival rates were 91.8% and 78.5%, respectively. CONCLUSION This strategy was feasible and resulted in excellent local tumor control. Serial plasma EBV DNA provides a noninvasive method of monitoring response in NPC.
Department of Clinical Oncology, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China. anthonytcchan@cuhk.edu.hk
Anthony T C
AT
Chan
Brigette B Y
BB
Ma
Y M Dennis
YM
Lo
S F
SF
Leung
W H
WH
Kwan
Edwin P
EP
Hui
Tony S K
TS
Mok
Michael
M
Kam
Lisa S
LS
Chan
Samuel K W
SK
Chiu
K H
KH
Yu
K Y
KY
Cheung
Karen
K
Lai
Maria
M
Lai
Frankie
F
Mo
Winnie
W
Yeo
Ann
A
King
Philip J
PJ
Johnson
Peter M L
PM
Teo
Benny
B
Zee
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016190:Carboplatin / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage*; D004279:DNA, Viral / Q000097:blood*; D004334:Drug Administration Schedule; D004784:Environmental Monitoring / Q000379:methods; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage*; D015996:Survival Rate
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004279:DNA, Viral; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin