Treatment of Childhood Nasopharyngeal Carcinoma With Induction Chemotherapy and Concurrent Chemoradiotherapy: Results of the Children's Oncology Group ARAR0331 Study

Abstract

Purpose: The treatment of childhood nasopharyngeal carcinoma has been adapted from adult regimens; pediatric-specific studies are limited. The ARAR0331 study sought to evaluate the impact of induction chemotherapy (IC) and concurrent chemoradiotherapy (CCR).

Patients and methods: Patients with American Joint Committee on Cancer stages IIb to IV were scheduled to receive three cycles of IC with cisplatin and fluorouracil, followed by CCR with three cycles of cisplatin. Patients with complete or partial response to IC received 61.2 Gy to the nasopharynx and neck, and patients with stable disease received 71.2 Gy.

Results: Between February 2006 and January 2012, 111 patients (75 male) were enrolled. Median age was 15 years, and 46.8% of the patients were African American. After a feasibility analysis, the study was amended to reduce cisplatin to two cycles during CCR. The 5-year event-free survival (EFS) and overall survival estimates were 84.3% and 89.2%, respectively. The 5-year EFS for stages IIb, III, and IV were 100%, 82.8%, and 82.7%, respectively. The 5-year cumulative incidence estimates of local, distant, and combined relapse were 3.7%, 8.7%, and 1.8%, respectively. Patients treated with three versus two CCR cycles of cisplatin had improved 5-year postinduction EFS (90.7% v 81.2%, P = .14).

Conclusion: Patients in ARAR0331 were characterized by advanced disease and by a high proportion of black children and adolescents. Treatment with IC and CRT resulted in excellent outcomes. A radiation dose reduction is possible for patients responding to IC. Although the outcomes are comparable, we observed a trend toward decreased EFS for patients assigned to receive fewer doses of cisplatin during CCR.

Trial registration: ClinicalTrials.gov NCT00274937.

FIG 1.

CONSORT diagram of ARAR0331. XRT, radiation therapy.

FIG 2.

Event-free survival and overall survival probabilities for 111 patients enrolled in ARAR0331.

FIG 3.

Event-free survival probabilities by stage.

FIG 4.

Cumulative incidence of relapse by type.

FIG 5.

Cumulative incidence of types of relapse after induction according to planned consolidation therapy. The red dashed line represents assignment to two cycles of cisplatin; the blue solid line represents three cycles of cisplatin.