Preradiation chemotherapy with methotrexate, cisplatin, 5-fluorouracil, and leucovorin for pediatric nasopharyngeal carcinoma.
BACKGROUND
Nasopharyngeal carcinoma (NPC) is rare in children, accounting for <1% of all cases. Treatment most commonly includes radiotherapy but long-term side effects of such treatment can produce devastating cosmetic and functional sequelae in children. Chemotherapy may help to decrease the radiotherapy dose and limit the side effects of local therapies. However, little is known regarding the chemosensitivity of NPC tumors in pediatric patients.


METHODS
Patients with American Joint Committee on Cancer (AJCC) Stage I/II disease (Stratum 01) received irradiation only. Patients with AJCC Stage III/IV disease (Stratum 02) received 4 courses of preradiation chemotherapy comprising methotrexate (120 mg/m2) on Day 1, with cisplatin (100 mg/m2) 24 hours later, 5-fluorouracil 1000 mg/m2 per day as a continuous infusion for 3 days, and leucovorin 25 mg/m2 every 6 hours for 6 doses. Irradiation was given after chemotherapy and consisted of 50.4 gray (Gy) to the upper neck and 45.0 Gy to the lower neck, with a boost to the primary tumor and positive lymph nodes for a total dose of 61.2 Gy.


RESULTS
One patient was enrolled in Stratum 01 and 16 evaluable patients were enrolled in Stratum 02. The median age of the patients was 13 years and 65% of the patients were black. All patients tested had evidence of Epstein-Barr virus infection. Two-thirds of the patients developed Grade 3-4 mucositis during chemotherapy. The overall response rate to induction chemotherapy was 93.7%. The overall 4-year event-free and overall survival rates (+/- the standard error) were 77%+/-12% and 75%+/-12%, respectively.


CONCLUSIONS
The current study demonstrated that childhood NPC was sensitive to chemotherapy and that chemotherapy before irradiation was feasible. Future trials should investigate equivalent efficacy with a reduced radiotherapy dose.
Rodriguez-Galindo
Carlos
C
Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. carlos.rodriguez-galindo@stjude.org
Wofford
Marcia
M
Castleberry
Robert P
RP
Swanson
Gregory P
GP
London
Wendy B
WB
Fontanesi
James
J
Pappo
Alberto S
AS
Douglass
Edwin C
EC
D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002277:Carcinoma / Q000188:drug therapy* / Q000821:virology; D002945:Cisplatin / Q000009:adverse effects; D003131:Combined Modality Therapy; D020031:Epstein-Barr Virus Infections; D005472:Fluorouracil / Q000009:adverse effects; D004854:Herpesvirus 4, Human; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects; D008727:Methotrexate / Q000009:adverse effects; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000821:virology; D015996:Survival Rate
D000970:Antineoplastic Agents; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate