Radiation Therapy, Amifostine, and Chemotherapy in Treating Young Patients With Newly Diagnosed Nasopharyngeal Cancer
Radiation Therapy, Amifostine, and Chemotherapy in Treating Young Patients With Newly Diagnosed Nasopharyngeal Cancer
This phase III trial is studying how well radiation therapy, amifostine, and chemotherapy
 work in treating young patients with newly diagnosed nasopharyngeal cancer. Radiation therapy
 uses high-energy x-rays to kill tumor cells. Drugs, such as amifostine, may protect normal
 cells from the side effects of radiation therapy. Drugs used in chemotherapy, such as
 cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either
 by killing the cells or by stopping them from dividing. Giving radiation therapy together
 with amifostine and chemotherapy may kill more tumor cells.
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