Radiation Therapy, Amifostine, and Chemotherapy in Treating Young Patients With Newly Diagnosed Nasopharyngeal Cancer

PRIMARY OBJECTIVES:

I. Determine the response rate, overall survival, and event-free survival of children with
advanced nasopharyngeal carcinoma who are treated with induction chemotherapy followed by
concurrent chemoradiotherapy and amifostine.

SECONDARY OBJECTIVES:

I. Characterize the role of Epstein-Barr virus (EBV) in the pathogenesis of nasopharyngeal
carcinoma in children.

II. Investigate the predictive value of the detection of EBV DNA in the peripheral blood of
children with nasopharyngeal carcinoma.

III. Determine the incidence of NUT rearrangements in childhood nasopharyngeal carcinoma.

IV. Determine the radioprotective effect of amifostine when given daily prior to radiation
therapy.

OUTLINE: This is a nonrandomized, multicenter study. Patients are stratified according to
stage of disease (I or IIA [stratum I] vs IIB-IV [stratum II]).

STRATUM I: Patients undergo radiotherapy 5 days a week for 8 weeks. Patients also receive
amifostine subcutaneously on the same days they undergo radiotherapy.

STRATUM II:

INDUCTION THERAPY (weeks 1-9): Patients receive cisplatin IV over 6 hours on day 1 and
fluorouracil IV continuously on days 1-4. Treatment repeats every 3 weeks for 3 courses in
the absence of disease progression or unacceptable toxicity. Patients with responding or
stable disease proceed to consolidation therapy.

CONSOLIDATION THERAPY (weeks 10-18): Patients undergo radiotherapy and receive amifostine as
in stratum I. Patients also receive cisplatin IV over 6 hours on days 1 and 22 (2 courses).

After completion of study treatment, patients are followed periodically for 10 years.

Inclusion Criteria:

- Histological diagnosis of nasopharyngeal carcinoma WHO type II or III

- Stage I-IV disease

- Newly diagnosed disease

- Performance status

- Patients ≤ 16 years of age: Lansky 60-100%

- Patients > 16 years of age: Karnofsky 60-100%

- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min

- Creatinine based on age/gender as follows:

- No greater than 0.4 mg/dL (for patients 1 month to < 6 months of age)

- No greater than 0.5 mg/dL (for patients 6 months to < 1 year of age)

- No greater than 0.6 mg/dL (for patients 1-2 years of age)

- No greater than 0.8 mg/dL (for patients < 6 years of age)

- No greater than 1.0mg/dL (for patients 6 to < 10 years of age)

- No greater than 1.2 mg/dL (for patients 10 to < 13 years of age)

- No greater than 1.4 mg/dL (for female patients 13 to ≥ 16 years of age)

- No greater than 1.5 mg/dL (for male patients 13 to < 16 years of age)

- No greater than 1.7 mg/dL (for male patients ≥ 16 years of age)

- Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age

- AST or ALT < 2.5 times ULN for age

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No prior chemotherapy or radiotherapy to the nasopharynx or neck for the treatment of
nasopharyngeal carcinoma