Comparing three induction chemotherapy regimens for patients with locoregionally advanced nasopharyngeal carcinoma based on TNM stage and plasma Epstein–Barr virus DNA level

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Abstract

Background

We compared the efficacy and toxicity of three IC regimens (TPF: taxanes, cisplatin, and 5-fluorouracil; TP: taxanes and cisplatin; and PF: cisplatin and 5-fluorouracil) followed by CCRT in locoregionally advanced NPC.

Methods

The retrospective study involved 1354 patients with newly diagnosed stage III-IVA NPC treated with IC and CCRT. The median follow-up time in our cohort was 50 months. Based on EBV DNA level, all the patients with stage IV were divided into low- (pre-EBV DNA < 1500 copies) and high-risk group (pre-EBV DNA ≥ 1500 copies). Progression free survival (PFS), overall survival (OS), locoregional relapse free survival (LRFS), distant metastasis free survival (DMFS) and grade 3–4 toxicities were compared among different IC regimens. The survival rates were compared using log-rank test and a Cox proportional hazards model was used to perform multivariate analyses.

Results

A multivariate analysis revealed TPF to be more effective than TP. Among stage III patients, no significant difference in clinical outcome between the different IC regimens was showed, while TPF was associated with significantly better survival conditions in the stage IV patients. A further subgroup analysis revealed that only patients with pre-EBV DNA ≥ 1500 copies could benefit from the application of TPF among stage IV NPC. In terms of acute toxicities, PF was associated with fewer grade 3/4 acute toxicities.

Conclusions

In low-risk NPC patients, PF-based IC showed similar efficacy as TPF and TP but was associated with fewer grade 3/4 acute toxicities. In high-risk patients, however, the TPF regimen was superior to PF and TP, although grade 3/4 toxicities were more common with the TPF regimen.

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Most cited references 26

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Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099.

M Al-Sarraf, M. Leblanc, P Giri … (1998)

The Southwest Oncology Group (SWOG) coordinated an Intergroup study with the participation of Radiation Therapy Oncology Group (RTOG), and Eastern Cooperative Oncology Group (ECOG). This randomized phase III trial compared chemoradiotherapy versus radiotherapy alone in patients with nasopharyngeal cancers. Radiotherapy was administered in both arms: 1.8- to 2.0-Gy/d fractions Monday to Friday for 35 to 39 fractions for a total dose of 70 Gy. The investigational arm received chemotherapy with cisplatin 100 mg/m2 on days 1, 22, and 43 during radiotherapy; postradiotherapy, chemotherapy with cisplatin 80 mg/m2 on day 1 and fluorouracil 1,000 mg/m2/d on days 1 to 4 was administered every 4 weeks for three courses. Patients were stratified by tumor stage, nodal stage, performance status, and histology. Of 193 patients registered, 147 (69 radiotherapy and 78 chemoradiotherapy) were eligible for primary analysis for survival and toxicity. The median progression-free survival (PFS) time was 15 months for eligible patients on the radiotherapy arm and was not reached for the chemo-radiotherapy group. The 3-year PFS rate was 24% versus 69%, respectively (P < .001). The median survival time was 34 months for the radiotherapy group and not reached for the chemo-radiotherapy group, and the 3-year survival rate was 47% versus 78%, respectively (P = .005). One hundred eighty-five patients were included in a secondary analysis for survival. The 3-year survival rate for patients randomized to radiotherapy was 46%, and for the chemoradiotherapy group was 76% (P < .001). We conclude that chemoradiotherapy is superior to radiotherapy alone for patients with advanced nasopharyngeal cancers with respect to PFS and overall survival.

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A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs. conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma.

Gang Peng, Tao Wang, Kun-Yu Yang … (2012)

To compare clinical outcomes and toxicities of two-dimensional conventional radiation therapy (2D-CRT) and intensity modulated radiation therapy (IMRT) for the treatment of nasopharyngeal carcinoma (NPC). Between July 2003 and October 2008, 616 patients with non-metastatic stage I to IVb NPC were prospectively randomized to receive 2D-CRT (n=310; mean age, 44.8±13.6 years) or IMRT (n=306; mean age, 46.7±12.5 years). Clinical outcomes and acute and late toxicities were determined and compared. The 2 groups were comparable with respect to all parameters of demographics and disease characteristics (all, p>0.05). Median follow-up was 42 months (range, 1-83 months). The 5-year actuarial local control rate was 90.5% in the IMRT group and 84.7% in the 2D-CRT group. The local control rates were 91% for stage T3 and 81.5% for stage T4 disease in the IMRT group and 80% and 62.2% in the 2D-CRT group, respectively. The 5-year actuarial nodal relapse-free survival (NRFS) rate was 92.4% in the IMRT and 92.9% in the 2D-CRT group (p>0.05). The NRFS was 93.9% for N2 disease in the IMRT group and 91.4% in the 2D-CRT group (p=0.02). The 5-year overall survival (OS) rate was 79.6% for the IMRT group and 67.1% for the 2D-CRT group (p=0.001). When stratified for stage, a significant difference was only noted for stage III disease. In terms of radiation-induced toxicities, patients in IMRT group had significantly lower radiation-induced toxicities than those in 2D-CRT group. IMRT provides improved local-recurrence free survival, especially in late-stage NPC patients and is associated with a lower incidence of toxicities. Copyright © 2012. Published by Elsevier Ireland Ltd.

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Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival.

Jin-Ching Lin, Jian-Sheng Jan, Chen-Yi Hsu … (2003)

Nasopharyngeal carcinoma (NPC) is a radiosensitive and chemosensitive tumor. This randomized phase III trial compared concurrent chemoradiotherapy (CCRT) versus radiotherapy (RT) alone in patients with advanced NPC. From December 1993 to April 1999, 284 patients with 1992 American Joint Committee on Cancer stage III to IV (M0) NPC were randomly allocated into two arms. Similar dosage and fractionation of RT was administered in both arms. The investigational arm received two cycles of concurrent chemotherapy with cisplatin 20 mg/m(2)/d plus fluorouracil 400 mg/m(2)/d by 96-hour continuous infusion during the weeks 1 and 5 of RT. Survival analysis was estimated by the Kaplan-Meier method and compared by the log-rank test. Baseline patient characteristics were comparable in both arms. After a median follow-up of 65 months, 26.2% (37 of 141) and 46.2% (66 of 143) of patients developed tumor relapse in the CCRT and RT-alone groups, respectively. The 5-year overall survival rates were 72.3% for the CCRT arm and 54.2% for the RT-only arm (P =.0022). The 5-year progression-free survival rates were 71.6% for the CCRT group compared with 53.0% for the RT-only group (P =.0012). Although significantly more toxicity was noted in the CCRT arm, including leukopenia and emesis, compliance with the combined treatment was good. The second cycle of concurrent chemotherapy was refused by nine patients and was delayed for > or = 1 week for another nine patients. There were no treatment-related deaths in either arm. We conclude that CCRT is superior to RT alone for patients with advanced NPC in endemic areas.

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Author and article information

Contributors

Sai-Lan Liu: liusl@sysucc.org.cn

Xue-Song Sun: sunxs@sysucc.org.cn

Hao-Jun Xie: xiehj@sysucc.org.cn

Qiu-Yan Chen: chenqy@sysucc.org.cn

Huan-Xin Lin: linhx@sysucc.org.cn

Hu Liang: lianghu@sysucc.org.cn

Yu-Jing Liang: liangyuj@sysucc.org.cn

Xiao-Yun Li: lixy1@sysucc.org.cn

Jin-Jie Yan: yanjj@sysucc.org.cn

Chao Lin: linchao@sysucc.org.cn

Zhen-Chong Yang: yangzc@sysucc.org.cn

Shan-Shan Guo: guoshsh@sysucc.org.cn

Li-Ting Liu: liult@sysucc.org.cn

Qing-Nan Tang: tangqn@sysucc.org.cn

Yu-Yun Du: duyy@sysucc.org.cn

Lin-Quan Tang: tanglq@sysucc.org.cn

Ling Guo: guoling@sysucc.org.cn

Hai-Qiang Mai: maihq@sysucc.org.cn

Journal

Journal ID (nlm-ta): BMC Cancer

Journal ID (iso-abbrev): BMC Cancer

Title: BMC Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2407

Publication date (Electronic): 3 February 2020

Publication date PMC-release: 3 February 2020

Publication date Collection: 2020

Volume: 20

Electronic Location Identifier: 89

Affiliations

[1 ]Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, 651 Dongfeng Road East, Guangzhou, 510060 People’s Republic of China

[2 ]ISNI 0000 0004 1803 6191, GRID grid.488530.2, Department of Nasopharyngeal Carcinoma, , Sun Yat-sen University Cancer Center, ; 651 Dongfeng Road East, Guangzhou, 510060 People’s Republic of China

[3 ]ISNI 0000 0004 1803 6191, GRID grid.488530.2, Department of Radiation Oncology, , Sun Yat-sen University Cancer Center, ; 651 Dongfeng Road East, Guangzhou, 510060 People’s Republic of China

Article

Publisher ID: 6555

DOI: 10.1186/s12885-020-6555-7

PMC ID: 6998839

PubMed ID: 32013967

SO-VID: 52b0f1e4-4831-43b1-8016-ad433850843c

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 13 March 2019

Date accepted : 20 January 2020

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: nasopharyngeal carcinoma,induction chemotherapy,prognosis,plasma epstein–barr virus

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: nasopharyngeal carcinoma, induction chemotherapy, prognosis, plasma epstein–barr virus

Comparing three induction chemotherapy regimens for patients with locoregionally advanced nasopharyngeal carcinoma based on TNM stage and plasma Epstein–Barr virus DNA level

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Abstract

Background

Methods

Results

Conclusions

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Karger: Oncology

Most cited references 26

Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099.

A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs. conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma.

Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival.

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