Factors contributing to the efficacy of concurrent-adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma: Combined analyses of NPC-9901 and NPC-9902 Trials

Anne W.M. Lee, Stewart Y. Tung, Roger K.C. Ngan, Rick Chappell, Daniel T.T. Chua, T. X. Lu, Lillian Siu, Terence Tan, L. K. Chan, W. T. Ng, T. W. Leung, Y. T. Fu, Gordon K.H. Au, C. Zhao, Brian O'Sullivan, E. H. Tan, W. H. Lau

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Abstract

Background: The current standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) was conventional-fractionation radiotherapy plus concurrent-adjuvant chemotherapy as recommended by the Intergroup-0099 Study. This combined analysis of the NPC-9901 and the NPC-9902 Trials aims to provide more comprehensive data to evaluate the efficacy of the Intergroup-0099 regimen and the contributing factors. Methods: Eligible patients with stage III-IVB non-keratinizing NPC were randomly assigned to radiotherapy-alone (RT i group: 218 patients) or chemoradiotherapy (CRTi group: 223 patients) using cisplatin (100 mg/m2) for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m2) plus fluorouracil (1000 mg/m2/day for 4 days) for three cycles. The median follow-up was 6.1 years. Findings: Comparison by intention-to-treat showed that the CRTi group achieved significant improvement in overall failure-free rate (FFR), locoregional-FFR and cancer-specific survival (p ≤ 0.019); but the improvements for distant-FFR and overall survival (OS) were statistically insignificant (p ≥ 0.14). Further exploratory studies based on actual treatment showed that an additional improvement achieved was a significant gain in OS (CRTa versus RTa group: 72% versus 63% at 5-year, p = 0.037). Multivariate analyses showed that the dose of cisplatin during the concurrent phase had significant impact on locoregional-FFR and OS, while that of fluorouracil during the adjuvant phase was significant for distant-FFR. The 5-year locoregional-FFR for patients who received 0-1, 2 and 3 concurrent cycles were 79%, 88% and 88%, respectively; the corresponding distant-FFR by adjuvant cycles were 68%, 78% and 77%, respectively. Interpretation: Our results support the current practice of adding concurrent cisplatin plus adjuvant cisplatin-fluorouracil to radiotherapy for treating patients with locoregionally advanced NPC. The concurrent phase is important for locoregional control and survival, cisplatin 200 mg/m2 in two concurrent cycles might be adequate. Additional chemotherapy using fluorouracil-containing combination contributed to improving distant control.

Original languageEnglish (US)
Pages (from-to)656-666
Number of pages11
JournalEuropean Journal of Cancer
Volume47
Issue number5
DOIs
StatePublished - Mar 1 2011

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Adjuvant Chemotherapy
Cisplatin
Fluorouracil
Radiotherapy
Survival
Survival Rate
Chemoradiotherapy
Nasopharyngeal carcinoma
Multivariate Analysis
Drug Therapy
Therapeutics
Neoplasms

Keywords

  • Concurrent-adjuvant chemotherapy
  • Nasopharyngeal carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Factors contributing to the efficacy of concurrent-adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma : Combined analyses of NPC-9901 and NPC-9902 Trials. / Lee, Anne W.M.; Tung, Stewart Y.; Ngan, Roger K.C.; Chappell, Rick; Chua, Daniel T.T.; Lu, T. X.; Siu, Lillian; Tan, Terence; Chan, L. K.; Ng, W. T.; Leung, T. W.; Fu, Y. T.; Au, Gordon K.H.; Zhao, C.; O'Sullivan, Brian; Tan, E. H.; Lau, W. H.

In: European Journal of Cancer, Vol. 47, No. 5, 01.03.2011, p. 656-666.

Research output: Contribution to journalArticle

Lee, AWM, Tung, SY, Ngan, RKC, Chappell, R, Chua, DTT, Lu, TX, Siu, L, Tan, T, Chan, LK, Ng, WT, Leung, TW, Fu, YT, Au, GKH, Zhao, C, O'Sullivan, B, Tan, EH & Lau, WH 2011, 'Factors contributing to the efficacy of concurrent-adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma: Combined analyses of NPC-9901 and NPC-9902 Trials', European Journal of Cancer, vol. 47, no. 5, pp. 656-666. https://doi.org/10.1016/j.ejca.2010.10.026
Lee, Anne W.M. ; Tung, Stewart Y. ; Ngan, Roger K.C. ; Chappell, Rick ; Chua, Daniel T.T. ; Lu, T. X. ; Siu, Lillian ; Tan, Terence ; Chan, L. K. ; Ng, W. T. ; Leung, T. W. ; Fu, Y. T. ; Au, Gordon K.H. ; Zhao, C. ; O'Sullivan, Brian ; Tan, E. H. ; Lau, W. H. / Factors contributing to the efficacy of concurrent-adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma : Combined analyses of NPC-9901 and NPC-9902 Trials. In: European Journal of Cancer. 2011 ; Vol. 47, No. 5. pp. 656-666.
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abstract = "Background: The current standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) was conventional-fractionation radiotherapy plus concurrent-adjuvant chemotherapy as recommended by the Intergroup-0099 Study. This combined analysis of the NPC-9901 and the NPC-9902 Trials aims to provide more comprehensive data to evaluate the efficacy of the Intergroup-0099 regimen and the contributing factors. Methods: Eligible patients with stage III-IVB non-keratinizing NPC were randomly assigned to radiotherapy-alone (RT i group: 218 patients) or chemoradiotherapy (CRTi group: 223 patients) using cisplatin (100 mg/m2) for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m2) plus fluorouracil (1000 mg/m2/day for 4 days) for three cycles. The median follow-up was 6.1 years. Findings: Comparison by intention-to-treat showed that the CRTi group achieved significant improvement in overall failure-free rate (FFR), locoregional-FFR and cancer-specific survival (p ≤ 0.019); but the improvements for distant-FFR and overall survival (OS) were statistically insignificant (p ≥ 0.14). Further exploratory studies based on actual treatment showed that an additional improvement achieved was a significant gain in OS (CRTa versus RTa group: 72{\%} versus 63{\%} at 5-year, p = 0.037). Multivariate analyses showed that the dose of cisplatin during the concurrent phase had significant impact on locoregional-FFR and OS, while that of fluorouracil during the adjuvant phase was significant for distant-FFR. The 5-year locoregional-FFR for patients who received 0-1, 2 and 3 concurrent cycles were 79{\%}, 88{\%} and 88{\%}, respectively; the corresponding distant-FFR by adjuvant cycles were 68{\%}, 78{\%} and 77{\%}, respectively. Interpretation: Our results support the current practice of adding concurrent cisplatin plus adjuvant cisplatin-fluorouracil to radiotherapy for treating patients with locoregionally advanced NPC. The concurrent phase is important for locoregional control and survival, cisplatin 200 mg/m2 in two concurrent cycles might be adequate. Additional chemotherapy using fluorouracil-containing combination contributed to improving distant control.",
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T1 - Factors contributing to the efficacy of concurrent-adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma

T2 - Combined analyses of NPC-9901 and NPC-9902 Trials

AU - Lee, Anne W.M.

AU - Tung, Stewart Y.

AU - Ngan, Roger K.C.

AU - Chappell, Rick

AU - Chua, Daniel T.T.

AU - Lu, T. X.

AU - Siu, Lillian

AU - Tan, Terence

AU - Chan, L. K.

AU - Ng, W. T.

AU - Leung, T. W.

AU - Fu, Y. T.

AU - Au, Gordon K.H.

AU - Zhao, C.

AU - O'Sullivan, Brian

AU - Tan, E. H.

AU - Lau, W. H.

PY - 2011/3/1

Y1 - 2011/3/1

N2 - Background: The current standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) was conventional-fractionation radiotherapy plus concurrent-adjuvant chemotherapy as recommended by the Intergroup-0099 Study. This combined analysis of the NPC-9901 and the NPC-9902 Trials aims to provide more comprehensive data to evaluate the efficacy of the Intergroup-0099 regimen and the contributing factors. Methods: Eligible patients with stage III-IVB non-keratinizing NPC were randomly assigned to radiotherapy-alone (RT i group: 218 patients) or chemoradiotherapy (CRTi group: 223 patients) using cisplatin (100 mg/m2) for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m2) plus fluorouracil (1000 mg/m2/day for 4 days) for three cycles. The median follow-up was 6.1 years. Findings: Comparison by intention-to-treat showed that the CRTi group achieved significant improvement in overall failure-free rate (FFR), locoregional-FFR and cancer-specific survival (p ≤ 0.019); but the improvements for distant-FFR and overall survival (OS) were statistically insignificant (p ≥ 0.14). Further exploratory studies based on actual treatment showed that an additional improvement achieved was a significant gain in OS (CRTa versus RTa group: 72% versus 63% at 5-year, p = 0.037). Multivariate analyses showed that the dose of cisplatin during the concurrent phase had significant impact on locoregional-FFR and OS, while that of fluorouracil during the adjuvant phase was significant for distant-FFR. The 5-year locoregional-FFR for patients who received 0-1, 2 and 3 concurrent cycles were 79%, 88% and 88%, respectively; the corresponding distant-FFR by adjuvant cycles were 68%, 78% and 77%, respectively. Interpretation: Our results support the current practice of adding concurrent cisplatin plus adjuvant cisplatin-fluorouracil to radiotherapy for treating patients with locoregionally advanced NPC. The concurrent phase is important for locoregional control and survival, cisplatin 200 mg/m2 in two concurrent cycles might be adequate. Additional chemotherapy using fluorouracil-containing combination contributed to improving distant control.

AB - Background: The current standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) was conventional-fractionation radiotherapy plus concurrent-adjuvant chemotherapy as recommended by the Intergroup-0099 Study. This combined analysis of the NPC-9901 and the NPC-9902 Trials aims to provide more comprehensive data to evaluate the efficacy of the Intergroup-0099 regimen and the contributing factors. Methods: Eligible patients with stage III-IVB non-keratinizing NPC were randomly assigned to radiotherapy-alone (RT i group: 218 patients) or chemoradiotherapy (CRTi group: 223 patients) using cisplatin (100 mg/m2) for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m2) plus fluorouracil (1000 mg/m2/day for 4 days) for three cycles. The median follow-up was 6.1 years. Findings: Comparison by intention-to-treat showed that the CRTi group achieved significant improvement in overall failure-free rate (FFR), locoregional-FFR and cancer-specific survival (p ≤ 0.019); but the improvements for distant-FFR and overall survival (OS) were statistically insignificant (p ≥ 0.14). Further exploratory studies based on actual treatment showed that an additional improvement achieved was a significant gain in OS (CRTa versus RTa group: 72% versus 63% at 5-year, p = 0.037). Multivariate analyses showed that the dose of cisplatin during the concurrent phase had significant impact on locoregional-FFR and OS, while that of fluorouracil during the adjuvant phase was significant for distant-FFR. The 5-year locoregional-FFR for patients who received 0-1, 2 and 3 concurrent cycles were 79%, 88% and 88%, respectively; the corresponding distant-FFR by adjuvant cycles were 68%, 78% and 77%, respectively. Interpretation: Our results support the current practice of adding concurrent cisplatin plus adjuvant cisplatin-fluorouracil to radiotherapy for treating patients with locoregionally advanced NPC. The concurrent phase is important for locoregional control and survival, cisplatin 200 mg/m2 in two concurrent cycles might be adequate. Additional chemotherapy using fluorouracil-containing combination contributed to improving distant control.

KW - Concurrent-adjuvant chemotherapy

KW - Nasopharyngeal carcinoma

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