Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial

详细信息    查看全文

• 作者：Prof Jean Bourhis ; MD^a ; ^{bourhis@igr.fr} ; Christian Sire ; MD^d ; Pierre Graff ; MD^e ; Prof Vincent Gré ; goire ; MD^f ; Prof Philippe Maingon ; MD^g ; Prof Gilles Calais ; MD^h ; Bernard Gery ; MDⁱ ; Laurent Martin ; MD^j ; Marc Alfonsi ; MD^k ; Patrick Desprez ; MD^l ; Thierry Pignon ; MD^m ; Etienne Bardet ; MDⁿ ; Michel Rives ; MD^o ; Lionel Geoffrois ; MD^e ; Prof Nicolas Daly-Schveitzer ; MD^o ; Sok Sen ; MD^p ; Claude Tuchais ; MD^q ; Olivier Dupuis ; MD^r ; Sté ; phane Guerif ; MD^s ; Michel Lapeyre ; MD^t ; Vé ; ronique Favrel ; MD^u ; Prof Marc Hamoir ; MD^f ; Antoine Lusinchi ; MD^a ; Sté ; phane Temam ; MD^b ; Antonella Pinna ; BSc^c ; Yun Gan Tao ; MD^a ; Pierre Blanchard ; MD^a ; Anne Aupé ; rin ; MD^c
• 刊名：Lancet Oncology
• 出版年：2012
• 出版时间：February 2012
• 年：2012
• 卷：13
• 期：2
• 页码：145-153
• 全文大小：331 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

Background

Concomitant chemoradiotherapy and accelerated radiotherapy independently improve outcomes for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC). We aimed to assess the efficacy and safety of a combination of these approaches.

Methods

In our open-label phase 3 randomised trial, we enrolled patients with locally advanced, stage III and IV (non-metastatic) HNSCC and an Eastern Cooperative Oncology Group performance status of 0-2. We randomly allocated patients centrally with a computer program (with centre, T stage, N stage, and localisation as minimisation factors) in a 1:1:1 ratio to receive conventional chemoradiotherapy (70 Gy in 7 weeks plus three cycles of 4 days' concomitant carboplatin-fluorouracil), accelerated radiotherapy-chemotherapy (70 Gy in 6 weeks plus two cycles of 5 days' concomitant carboplatin-fluorouracil), or very accelerated radiotherapy alone (64¡¤8 Gy [1¡¤8 Gy twice daily] in 3¡¤5 weeks). The primary endpoint, progression-free survival (PFS), was assessed in all enrolled patients. This trial is completed. The trial is registered with , number .

Findings

Between Feb 29, 2000, and May 9, 2007, we randomly allocated 279 patients to receive conventional chemoradiotherapy, 280 to accelerated radiotherapy-chemotherapy, and 281 to very accelerated radiotherapy. Median follow-up was 5¡¤2 years (IQR 4¡¤9-6¡¤2); rates of chemotherapy and radiotherapy compliance were good in all groups. Accelerated radiotherapy-chemotherapy offered no PFS benefit compared with conventional chemoradiotherapy (HR 1¡¤02, 95 % CI 0¡¤84-1¡¤23; p=0¡¤88) or very accelerated radiotherapy (0¡¤83, 0¡¤69-1¡¤01; p=0¡¤060); conventional chemoradiotherapy improved PFS compared with very accelerated radiotherapy (0¡¤82, 0¡¤67-0¡¤99; p=0¡¤041). 3-year PFS was 37¡¤6 % (95 % CI 32¡¤1-43¡¤4) after conventional chemoradiotherapy, 34¡¤1 % (28¡¤7-39¡¤8) after accelerated radiotherapy-chemotherapy, and 32¡¤2 % (27¡¤0-37¡¤9) after very accelerated radiotherapy. More patients in the very accelerated radiotherapy group had RTOG grade 3-4 acute mucosal toxicity (226 [84 % ] of 268 patients) compared with accelerated radiotherapy-chemotherapy (205 [76 % ] of 271 patients) or conventional chemoradiotherapy (180 [69 % ] of 262; p=0¡¤0001). 158 (60 % ) of 265 patients in the conventional chemoradiotherapy group, 176 (64 % ) of 276 patients in the accelerated radiotherapy-chemotherapy group, and 190 (70 % ) of 272 patients in the very accelerated radiotherapy group were intubated with feeding tubes during treatment (p=0¡¤045).

Interpretation

Chemotherapy has a substantial treatment effect given concomitantly with radiotherapy and acceleration of radiotherapy cannot compensate for the absence of chemotherapy. We noted the most favourable outcomes for conventional chemoradiotherapy, suggesting that acceleration of radiotherapy is probably not beneficial in concomitant chemoradiotherapy schedules.

Funding

French Ministry of Health.