NPC‐0501 trial on the value of changing chemoradiotherapy sequence, replacing 5‐fluorouracil with capecitabine, and altering fractionation for patients with advanced nasopharyngeal carcinoma

Abstract

BACKGROUND: A current recommendation for the treatment of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) is conventional fractionated radiotherapy (RT) with concurrent cisplatin followed by adjuvant cisplatin and 5-fluorouracil (PF). This randomized NPC-0501 trial evaluated the therapeutic effect of changing to an induction-concurrent sequence or acceleratedfractionation sequence, and/or replacing 5-fluorouracil with capecitabine (X). METHODS: Patients with American Joint Committee on Cancer/International Union Against Cancer stage III to stage IVB NPC initially were randomly allocated to 1 of 6 treatment arms (6-arm full-randomization cohort). The protocol was amended in 2009 to permit centers to opt out of randomization regarding fractionation (3-arm chemotherapy cohort). RESULTS: A total of 803 patients were accrued (1 of whom was nonevaluable) from 2006 to 2012. Based on the overall comparisons, neither changing the chemotherapy sequence nor accelerated fractionation improved treatment outcome. However, secondary analyses demonstrated that when adjusted for RT parameters and other significant factors, the inductionconcurrent sequence, especially the induction-PX regimen, achieved significant improvements in progression-free survival (PFS) and overall survival. Efficacy varied among different RT groups: although no impact was observed in the accelerated-fractionation group and the 3-arm chemotherapy cohort, a comparison of the induction-concurrent versus concurrent-adjuvant sequence in the conventionalfractionation group demonstrated a significant benefit in PFS (78% vs 62% at 5 years; P = .015) and a marginal benefit in overall survival (84% vs 72%; P = .042) after adjusting for multiple comparisons. Comparison of the induction-PX versus the adjuvant-PF regimen demonstrated better PFS (78% vs 62%; P = .027) without an increase in overall late toxicity. CONCLUSIONS: For patients irradiated using conventional fractionation, changing the chemotherapy sequence from a concurrent-adjuvant to an induction-concurrent sequence, particularly using induction cisplatin and capecitabine, potentially could improve efficacy without an adverse impact on late toxicity. However, further validation is needed for confirmation of these findings.

Induction chemotherapy is the best timekeeper in nasopharyngeal carcinoma

“…Several studies and meta‐analyses have corroborated the results described by Lee et al 1 In the era of intensity‐modulated radiotherapy, a survival benefit was described in randomized clinical trials exploring the added value of induction cisplatin–based chemotherapy with either 5‐FU and docetaxel (the TPF regimen; hazard ratio for failure, 0.68) 8,12 or gemcitabine (stratified hazard ratio for death, 0.43) 7 . Apart from NPC‐0501, no direct comparisons between induction schedules have been published so far.…”

“…We congratulate Lee et al for their great efforts in conducting such an ambitious and complex randomized clinical trial, 1 and we are grateful for their sharing with the scientific community the updated results of their work formerly published by Cancer in 2015 2 …”

“…We congratulate Lee et al for their great efforts in conducting such an ambitious and complex randomized clinical trial, 1 and we are grateful for their sharing with the scientific community the updated results of their work formerly published by Cancer in 2015. 2 After a prolonged follow-up (median, 8.4 years), the study has concluded that induction is superior to adjuvant chemotherapy without an adverse impact from late toxicities.…”

Nasopharyngeal carcinoma: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up†

“…65 Long-term data from a multicentre, randomised, factorial trial showed that shifting from the concurrent-adjuvant to the induction-concurrent sequence achieved significant improvements in PFS and marginal improvements in OS without an adverse impact on late toxicity [II, B]. 66 The selection of patients to receive more ChT or immunotherapy in addition to CRT in the form of either ICT or AC is a therapeutic area that is being explored in ongoing randomised controlled trials (see below for individualised risk assessment).…”

Nasopharynx cancer: Induction or adjuvant? That is the question

“…In the current issue of Cancer , Lee et al 18 attempt to answer the aforementioned question and report a very complex, 6‐arm randomized trial comparing chemotherapy sequencing, types of chemotherapy, and radiation fractionation schedules. The authors are to be congratulated for conducting and completing this large multicenter trial.…”