Preliminary Results of Trial NPC-0501 Evaluating the Therapeutic Gain by Changing From Concurrent-Adjuvant to Induction-Concurrent Chemoradiotherapy, Changing From Fluorouracil to Capecitabine, and Changing From Conventional to Accelerated Radiotherapy Fractionation in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma
Publication in refereed journal


A current recommendation for locoregionally advanced nasopharyngeal carcinoma (NPC) is conventional fractionated radiotherapy with concurrent cisplatin plus adjuvant cisplatin and fluorouracil (PF). In this randomized trial, the authors evaluated the potential therapeutic benefit from changing to an induction‐concurrent chemotherapy sequence, replacing fluorouracil with oral capecitabine, and/or using accelerated rather than conventional radiotherapy fractionation.
Patients with stage III through IVB, nonkeratinizing NPC were randomly allocated to 1 of 6 treatment arms. The protocol was amended in 2009 to permit confining randomization to the conventional fractionation arms. The primary endpoint was progression‐free survival. Secondary endpoints included overall survival and safety.
In total, 803 patients were accrued, and 706 patients were randomly allocated to all 6 treatment arms. Comparisons of induction PF versus adjuvant PF did not indicate a significant improvement. Unadjusted comparisons of induction cisplatin and capecitabine (PX) versus adjuvant PF indicated a favorable trend in progression‐free survival for the conventional fractionation arm (P = .045); analyses that were adjusted for other significant factors and fractionation reflected a significant reduction in the hazards of disease progression (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.36‐0.80) and death (HR, 0.42; 95% CI, 0.25‐0.70). Unadjusted comparisons of induction sequences versus adjuvant sequences did not reach statistical significance, but adjusted comparisons indicated favorable improvements by induction sequence. Comparisons of induction PX versus induction PF revealed fewer toxicities (neutropenia and electrolyte disturbance), unadjusted comparisons of efficacy were statistically insignificant, but adjusted analyses indicated that induction PX had a lower hazard of death (HR, 0.57; 95% CI, 0.34‐0.97). Changing the fractionation from conventional to accelerated did not achieve any benefit but incurred higher toxicities (acute mucositis and dehydration).
Preliminary results indicate that the benefit of changing to an induction‐concurrent sequence remains uncertain; replacing fluorouracil with oral capecitabine warrants further validation in view of its convenience, favorable toxicity profile, and favorable trends in efficacy; and accelerated fractionation is not recommended for patients with locoregionally advanced NPC who receive chemoradiotherapy.
著者Lee AWM, Ngan RKC, Tung SY, Cheng A, Kwong DLW, Lu TX, Chan ATC, Chan LLK, Yiu H, Ng WT, Wong F, Yuen KT, Yau S, Cheung FY, Chan OSH, Choi H, Chappell R
詳細描述The Erratum to this article has been published in Cancer 2020 126(2):454-455 - "The authors have recently detected an error in the captioned article:

The original design of this trial (protocol dated September 2006) was to randomly allocate eligible patients in equal proportions to 1 of 6 arms (3 chemotherapy regimens and 2 radiation fractionations). However, the protocol was amended in 2009, following the recommendation of the independent Data Monitoring Committee, to permit centers with logistic difficulty to opt out of randomization on fractionation in order to improve accrual.

In the published manuscript, we stated “In this preliminary study, the core analyses on efficacy were based on the 706 patients randomized to all 6 arms as planned in the original study design.”

During the recent preparation of the final report with updated outcome data, we found that 5 centers had actually opted out of randomization on fractionation after the protocol revision in 2009. The number of patients equally randomized to all 6 arms was 578 (not 706 as stated in the published report in Cancer 2015).

Despite such discrepancy, the messages in the published article remain valid. The updated analyses of this 6‐Arms Randomization Cohort confirmed that (1) Accelerated‐Fractionation did not improve any efficacy endpoints for patients treated with chemo‐radiotherapy; furthermore, this negated the potential improvements by changing to induction‐concurrent regimen/sequence; and (2) in the Conventional‐Fractionation Group, Induction cisplatin‐capecitabine regimen achieved better progression‐free survival (PFS; 78% vs 62% at 5‐year, P = .027) than the Adjuvant cisplatin‐fluorouracil regimen.

The authors regret this error and wish to express their deepest apology."
頁次1328 - 1338
關鍵詞nasopharyngeal carcinoma, randomized controlled trial, chemoradiotherapy, capecitabine, accelerated fractionation
Web of Science 學科類別Oncology;Oncology

上次更新時間 2021-08-05 於 00:03