The additional value of chemotherapy to radiotherapy in locally advanced nasopharyngeal carcinoma: a meta-analysis of the published literature. J Clin Oncol

Department of Radiation Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Journal of Clinical Oncology (Impact Factor: 18.43). 12/2004; 22(22):4604-12. DOI: 10.1200/JCO.2004.10.074
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The purpose of this meta-analysis was to determine the additional value of neoadjuvant, concurrent, and/or adjuvant chemotherapy to radiation in the treatment of locally advanced nasopharyngeal carcinoma (NPC) with regard to the overall survival (OS) and the incidence of local-regional recurrences (LRR) and distant metastases (DM).
To be eligible, full published studies had to deal with biopsy-proven NPC and have patients randomly assigned to receive conventional radiotherapy (66 to 70 Gy in 7 weeks) or radiotherapy combined with chemotherapy.
Ten randomized clinical studies were identified, including 2,450 patients. The pooled hazard ratio (HR) of death for all studies was 0.82 (95% CI, 0.71 to 0.95; P = .01) corresponding to an absolute survival benefit of 4% after 5 years. Three categories of trials were defined according to the sequence of chemotherapy, including neoadjuvant chemotherapy, at least concomitant chemoradiotherapy, and adjuvant chemotherapy. A significant interaction term (P = .02) was found among these three categories. The largest effect was found for concomitant chemotherapy, with a pooled HR of 0.48 (95% CI, 0.32 to 0.72), which corresponds to a survival benefit of 20% after 5 years. Comparable results were found for the incidence of LRR and DM.
The results of this study indicate that concomitant chemotherapy in addition to radiation is probably the most effective way to improve OS in NPC.

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Available from: Berend J Slotman,
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    • "In this context, concurrent chemoradiotherapy (CCRT) and hyperfractionated RT have been used for SCCHN, and the efficacy of CCRT using hyperfractionated RT was confirmed in a meta-analysis (Budach et al. 2006). There have been only a few reports that have investigated whether the overall treatment time or completion rate of concurrent chemotherapy is a prognostic factor in SCCHN patients treated with CCRT using conventional fractionated RT (Pignon et al. 2000; Langendijk et al. 2004). However, to the best of our knowledge, there have been no reports that have evaluated the prognostic impact of the overall treatment time or completion rate of concurrent chemotherapy in patients treated with CCRT using hyperfractionated RT. "
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    ABSTRACT: The purpose of this study was to investigate whether the overall treatment time and completion rates of chemotherapy were predictive factors for the survival rates in patients with squamous cell carcinoma of the head and neck (SCCHN) who were treated with concurrent chemoradiotherapy (CCRT) using hyperfractionated radiotherapy (RT) and daily carboplatin. The number of intermission days of RT were as follows; 0 (n = 37), 1-5 (n = 8), 6-10 (n = 12) and ≥11 (n = 12), and the days of RT without carboplatin; 0 (n = 27), 1-5 (n = 13), 6-10 (n = 13) and ≥7 (n = 16). The overall treatment time (≤48 vs ≥49 days) was a significant prognostic factor for the local control, disease-free survival and overall survival rates. The completion rate of chemotherapy, as the number of days of RT without carboplatin, was not a significant factor affecting any of the survival rates. In discussion, the strengths of the present study contain that all the patients were treated with 72 Gy delivered as 1.2 Gy twice daily, and received concurrent chemotherapy comprising daily carboplatin as a radio-sensitizer. Based on the results, the completion rate of chemotherapy may have a lower impact on the local control rate in comparison with the overall treatment time. We believe that when a treatment interruption is needed because of the acute toxicities, hyperfractionated RT should be resumed as soon as possible independently while continuing the break of daily carboplatin. The overall treatment time influenced the clinical outcomes in SCCHN patients treated with hyperfractionated CCRT using carboplatin, while the impact of the completion rates of daily carboplatin was limited. Sixty-nine consecutive patients with SCCHN were initially treated with definitive CCRT and were retrospectively analyzed. All 69 patients were treated with CCRT using hyperfractionated RT of 72 Gy in 60 fractions and daily carboplatin (25 mg/m(2)). The patients treated with other chemotherapeutic regimens or induction chemotherapy were excluded. On the intermission days of the RT, carboplatin was not prescribed. After the intermission, CCRT using RT plus daily carboplatin or RT alone was resumed.
    SpringerPlus 08/2015; 4(1):446. DOI:10.1186/s40064-015-1244-8
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    • "Prognostic factors correlated with disease-free survival (DFS) included: nodal size and stage, TNM stage, radiation dose, and response to chemotherapy [11] [12] [13]. Treatment related toxicity after a radiotherapy dose of 50– 70 Gy in pediatric and adolescents includes: xerostomia, neck fibrosis, dental caries, trismus, hypopituitarism, stunted growth, and hypothyroidism [1]. "
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    ABSTRACT: Investigate treatment outcome, prognostic factors and survival among selected group of Egyptian pediatric nasopharyngeal carcinoma patients. Thirty patients treated from non-metastatic nasopharyngeal carcinoma between 1997 and 2012 were retrospectively evaluated including: TNM staging, chemo-radiotherapy regimens. Survival analysis was done using Kaplan-Meier survival curves. Twenty-three males and 7 females (M:F 3.2:1) with median age of 14years; 84% with stages III/IV. Neck node enlargement was reported in 90% (27/30). Induction chemotherapy followed by radiotherapy was implemented in 80% of patients. Mucositis (87%) was the commonest treatment related toxicity. Nineteen patients (63%) were in CR with a median FU of 69months (range 24-160). Eleven patients had treatment local and distant failures (2 local, 7 distant and 2 local/distant) at a median FU of 24 and 34months respectively. 5-year overall and event-free survival rates were 77% and 63% respectively. Prolonged OAP of RT⩾50days, Hb<11g% and T4 stage affected EFS and OAS on UVA; while on MVA; prolonged OAP of RT⩾50days (p=0.002) and T4 stage (p=0.004) affected EFS and only Hb<11g% (p=0.019) affected OAS. Late toxicity was reported in 70% of irradiated patients. Radio-chemotherapy management for pediatric NPC resulted in comparable treatment outcomes with tolerable late effects. Response adapted radio-chemotherapy regimens in addition to the potential use of IMRT should be recommended to decrease treatment related side effects. Prolonged OAP of RT⩾50days and low Hb level were encountered as adverse prognostic factors; findings that need further investigation. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.
    Journal of the Egyptian National Cancer Institute 07/2015; 27(3). DOI:10.1016/j.jnci.2015.06.004
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    • "The current standard of care involves cisplatin-based concurrent chemotherapy (CRT), which has been shown to significantly improve survival [6] [7] [8]. "
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    ABSTRACT: Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CRT-A) is often the regimen of choice in locoregionally advanced nasopharyngeal carcinoma (NPC). Many alternative regimens have been reported in the literature, however, it is unknown how effective these regimens are compared to each other due to the lack of direct comparisons. Our objective was to perform a network meta-analysis (NMA) to determine the relative survival benefits of these treatments for locoregionally advanced NPC. We performed a systematic review following the Cochrane methodology, using MEDLINE, EMBASE and CENTRAL to identify all randomised controlled trials (RCTs) that compared different chemoradiotherapy regimens for locoregionally advanced NPC. Overall survival (OS) was the primary outcome of interest, and hazard ratios (HRs) were extracted using the Parmar method. Bayesian NMAs with random effects were conducted using WinBUGS. Twenty-five RCTs (5576 patients) were included in this review. All together, these trials compared seven different regimens: radiotherapy (RT), concurrent chemoradiotherapy (CRT), neoadjuvant followed by CRT (N-CRT), CRT-A, RT-A, N-RT and N-RT-A. All regimens that contained CRT performed significantly better than RT. CRT-A did not improve survival compared to CRT alone (0.98; 95% credible regions: 0.71-1.34). For N-CRT versus CRT, the HR was 1.03 (0.69-1.47). When CRT-A was compared against N-CRT, the resulting HR was 0.96 (0.64-1.48). Adjuvant chemotherapy does not appear to improve survival following CRT. The efficacies of CRT, CRT-A and N-CRT all appeared to be similar. Further studies are warranted to determine the value of additional chemotherapy phases in specific patient subgroups. Copyright © 2015 Elsevier Ltd. All rights reserved.
    European journal of cancer (Oxford, England: 1990) 06/2015; 15(12). DOI:10.1016/j.ejca.2015.04.027 · 5.42 Impact Factor
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