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Do all patients with advanced N-stage nasopharyngeal carcinoma benefit from the addition of induction chemotherapy to concurrent chemoradiotherapy?

ABSTRACT: Background:The aim of this study was to evaluate the benefits from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in N2-3 nasopharyngeal carcinoma (NPC). Methods:A total of 3089 patients with nonmetastatic NPC, staged as N2-3 were retrospectively reviewed. IC contained cisplatin (80?mg/m2) with 5-fluorouracil (800?mg/m2/day over 120 h), or cisplatin (80?mg/m2) with docetaxel (80?mg/m2), or cisplatin (60?mg/m2) with 5-fluorouracil (600?mg/m2 over 120 h), and docetaxel (60?mg/m2) administered at 3-week intervals for two or three cycles. Concurrent chemotherapy consisted of cisplatin (80 or 100?mg/m2) given in weeks 1, 4, and 7 of radiotherapy, or cisplatin (40?mg/m2) given weekly during radiotherapy. Overall, three well-matched risk groups (low, intermediate, and high risk) were created using propensity score matching, and IC plus CCRT was compared with CCRT in each risk group. Our primary endpoint was distant metastasis-free survival (DMFS). Results:A nomogram for DMFS was established with good prognostic accuracy (C-index, 0.69; 95% confidence interval, 0.64-0.73). The survival curves for low, intermediate, and high-risk groups stratified by the nomogram were significantly different between all three risk groups, with corresponding 5-year DMFS rates of 90.7%, 79.4%, and 64.9%, respectively (p < 0.001). IC plus CCRT was significantly associated with superior DMFS as compared with CCRT alone (69.5% versus 56.7%, p = 0.004) in the high-risk group. However, no significant difference between IC plus CCRT and CCRT was observed (p = 0.831 and 0.608, respectively) in the intermediate and low-risk groups. Conclusions:Our findings can help accurately guide the treatment of individual patients with advanced N-stage NPC.

SUBMITTER: Yao JJ

PROVIDER: S-EPMC6431774 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Do all patients with advanced N-stage nasopharyngeal carcinoma benefit from the addition of induction chemotherapy to concurrent chemoradiotherapy?

Yao Ji-Jin JJ Jin Ya-Nan YN Liu Zhi-Gang ZG Liu Qiao-Dan QD Pei Xiao-Feng XF Zhou Huai-Li HL Zhang Wang-Jian WJ Zhang Fan F Lin Li L Lawrence Wayne R WR Wang Si-Yang SY Ma Jun J Zhou Guan-Qun GQ Sun Ying Y

Therapeutic advances in medical oncology 20190321

<h4>Background</h4>The aim of this study was to evaluate the benefits from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in N2-3 nasopharyngeal carcinoma (NPC).<h4>Methods</h4>A total of 3089 patients with nonmetastatic NPC, staged as N2-3 were retrospectively reviewed. IC contained cisplatin (80 mg/m<sup>2</sup>) with 5-fluorouracil (800 mg/m<sup>2</sup>/day over 120 h), or cisplatin (80 mg/m<sup>2</sup>) with docetaxel (80 mg/m<sup>2</sup>), or cisplatin (6 ...[more]

PMID: 30923578

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Project description:PurposeInduction chemotherapy plus concurrent chemoradiotherapy and concurrent chemoradiotherapy alone are both standard treatment regimens for managing locally advanced nasopharyngeal carcinoma. However, the results of comparisons between them in clinical trials vary. Therefore, we designed this meta-analysis to illustrate their advantages and disadvantages in patients with locally advanced nasopharyngeal carcinoma.MethodsWe thoroughly searched the PubMed, EMBASE, and Cochrane Library databases and then merged the effect indicators of hazard ratios and risk ratios using RevMan 5.1.ResultsSeven randomized controlled trials totaling 2,319 patients were included in our research. The synthesized results showed that induction chemotherapy plus concurrent chemoradiotherapy improved overall survival (HR = 0.75, 95% CI: 0.63-0.89, P = 0.001), progression-free survival (HR = 0.69, 95% CI: 0.60-0.80, P < 0.001), distant metastasis-free survival (HR = 0.65, 95% CI: 0.53-0.80, P < 0.001) and locoregional recurrence-free survival (HR = 0.68 95%, CI: 0.54-0.86, P = 0.001) versus concurrent chemoradiotherapy alone. It also increased the risk of anemia, thrombocytopenia, and neutropenia during concurrent chemoradiotherapy. However, the incidence of leukopenia and mucositis was similar in induction chemotherapy and induction chemotherapy plus concurrent chemoradiotherapy. Furthermore, the subgroup analysis showed better survival outcomes with induction chemotherapy plus concurrent chemoradiotherapy than with concurrent chemoradiotherapy alone in the triweekly cisplatin subgroup (all P < 0.01), whereas induction chemotherapy plus concurrent chemoradiotherapy could only improve progression-free survival and locoregional recurrence-free survival in the weekly cisplatin subgroup (HR = 0.78, P = 0.02; and HR = 0.66, P = 0.03, respectively).ConclusionsInduction chemotherapy plus concurrent chemoradiotherapy improved survival outcomes in patients with locally advanced nasopharyngeal carcinoma versus concurrent chemoradiotherapy. For the weekly cisplatin regimen subgroup, it did not improve remote control or overall survival versus concurrent chemoradiotherapy alone, warranting further clarification.

Project description:PurposeThis large population-based analysis aims to investigate whether the additional induction chemotherapy to concurrent chemoradiotherapy improved overall survival (OS) and disease-free survival (DFS) for locoregionally advanced nasopharyngeal carcinoma (LRANPC).Patients and methodsThe study group comprised 3,980 patients who were treated either with IC+CCRT (1,888 patients) or CCRT alone (2,092 patients) between January 1998 and June 2013. Survival outcomes were compared using Cox proportional hazards regression models with adjustments for confounding provided by propensity score methods. Primary outcome variables included OS and DFS.ResultsKaplan-Meier analysis showed that CCRT and IC+CCRT were of similar benefit to OS (P=0.099), whereas there was a marginal benefit of CCRT to DFS (P=0.063) in the overall cohort, which showed no differences between the two treatment regimens using multivariate Cox analysis and propensity score. Interestingly, for patients with 2D radiationtherapy (2DRT), CCRT had OS and DFS benefits for stage III, with 5-year and 10-year OS for CCRT vs IC+CCRT being 88% and 75% vs 81% and 67%, respectively (P=0.002); 5-year and 10-year DFS for CCRT vs IC+CCRT being 84% and 74% vs 76% and 66%, respectively (P=0.002). In contrast, IC + CCRT had OS and DFS benefits for stage IVa-b, with 5-year and 10-year OS for CCRT vs IC+CCRT being 71% and 55% vs 76% and 60%, respectively (P=0.037, HR=0.786); 5-year and 10-year DFS for CCRT vs IC+CCRT were 64% and 50% vs 69% and 58%, respectively (P=0.038, HR=0.801). No difference was found in intensity-modulated radiotherapy (IMRT) subgroup.ConclusionOur study indicates that CCRT and IC+CCRT may have similar OS and DFS benefits for overall LRANPC. Stage-specific chemoradiotherapy may be administered based on the greatest benefit of IC+CCRT for stage IVa-b patients and CCRT alone for stage III patients received 2DRT. The optimal chemotherapy pattern in combination with IMRT needs further investigation.Trial registration ClinicalTrials.gov ID: NCT02604472.

Project description:BackgroundConcurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT-AC) is currently recommended as the standard treatment for locally advanced nasopharyngeal carcinoma (LA-NPC). Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy (NAC-CCRT) is an alternative strategy for decreasing tumor size and controlling micrometastases before main treatment. The aim of this study was to investigate and compare survival outcomes between LA-NPC patients treated with CCRT-AC and those treated with NAC-CCRT.MethodsThis retrospective cohort study included consecutive histologically confirmed LA-NPC patients that were treated with NAC-CCRT or CCRT-AC at Siriraj Hospital during the March 2010 to October 2014 study period. CCRT in both protocols consisted of 3-week cycles of cisplatin 100 mg/m2 with concurrent radiotherapy. Either NAC or AC consisted of 3-week cycles of cisplatin on day 1 and fluorouracil/leucovorin on days 1-4 for a maximum three cycles. The primary endpoint was 5-year overall survival (OS). Flexible parametric survival analysis was used, because the proportional hazards assumption of Cox regression was violated.ResultsOf the 266 LA-NPC patients that received treatment during the study period, 79 received NAC-CCRT and 187 received CCRT-AC. Median follow-up was 37 months. Significantly more patients with advanced clinical stage (stage IVA-IVB) received NAC-CCRT (86% in NAC-CCRT vs. 29% in CCRT-AC; p < 0.001). Compared to CCRT-AC in crude analysis, 3-year and 5-year OS of NAC-CCRT were 72% vs. 86% and 62% vs. 75% respectively (p = 0.059). Interestingly, the 3-year and 5-year post-estimation adjusted OS was 84% and 74% for NAC-CCRT and 81% and 70% for CCRT-AC, respectively (HR: 0.83, 95% confidence interval (CI): 0.45-1.56; p = 0.571). Also, adjusted analysis of distant-metastasis survival, NAC-CCRT showed HR was 0.79 (95% CI:0.37-1.72, p = 0.557). Conversely, adjusted analysis of locoregional relapse (LLR)-free survival revealed NAC-CCRT to have a significantly higher risk of LRR (HR: 2.18, 95% CI: 0.98-4.87; p = 0.057).ConclusionsThe results suggested that prognosis in the NAC-CCRT treated patients was not superior to that of the CCRT-AC treated individuals. In patients that receive neoadjuvant chemotherapy, locoregional relapse should be of concern. High-risk distant metastasis patients (N3 stage) that could achieve survival advantage from NAC-CCRT is an interesting and important topic for further study.

Project description:BackgroundN-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT).Patients and methodsBetween April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy.ResultsWith a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3-4 acute toxicities including bone marrow suppression (leukopenia: ?2 = 3.935, P = 0.047; anemia: ?2 = 9.760, P = 0.002; thrombocytopenia: ?2 = 8.821, P = 0.003), and both liver and renal dysfunction (?2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups.ConclusionIMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute toxicity rate.

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Do all patients with advanced N-stage nasopharyngeal carcinoma benefit from the addition of induction chemotherapy to concurrent chemoradiotherapy?

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Do all patients with advanced N-stage nasopharyngeal carcinoma benefit from the addition of induction chemotherapy to concurrent chemoradiotherapy?

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