Meta analysis| Volume 92, ISSUE 1, P4-14, July 2009

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Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients



      Our previous individual patient data (IPD) meta-analysis showed that chemotherapy improved survival in patients curatively treated for non-metastatic head and neck squamous cell carcinoma (HNSCC), with a higher benefit with concomitant chemotherapy. However the heterogeneity of the results limited the conclusions and prompted us to confirm the results on a more complete database by adding the randomised trials conducted between 1994 and 2000.


      The updated IPD meta-analysis included trials comparing loco-regional treatment to loco-regional treatment + chemotherapy in HNSCC patients and conducted between 1965 and 2000. The log-rank-test, stratified by trial, was used to compare treatments. The hazard ratios of death were calculated.


      Twenty-four new trials, most of them of concomitant chemotherapy, were included with a total of 87 trials and 16,485 patients. The hazard ratio of death was 0.88 (p < 0.0001) with an absolute benefit for chemotherapy of 4.5% at 5 years, and a significant interaction (p < 0.0001) between chemotherapy timing (adjuvant, induction or concomitant) and treatment. Both direct (6 trials) and indirect comparisons showed a more pronounced benefit of the concomitant chemotherapy as compared to induction chemotherapy. For the 50 concomitant trials, the hazard ratio was 0.81 (p < 0.0001) and the absolute benefit 6.5% at 5 years. There was a decreasing effect of chemotherapy with age (p = 0.003, test for trend).


      The benefit of concomitant chemotherapy was confirmed and was greater than the benefit of induction chemotherapy.


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      1. Ferlay F, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002: cancer incidence, mortality and prevalence worldwide. IARC Cancer Base No. 5. Version 2.0. Lyon: IARC Press; 2004.

        • Pignon J.-P.
        • Bourhis J.
        • Domenge C.
        • Désigné L.
        • On behalf of the MACH-NC Collaborative Group
        Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data.
        Lancet. 2000; 255: 949-955
        • Baujat B.
        • Mahé C.
        • Pignon J.-P.
        • Hill C.
        A graphical method for exploring heterogeneity in meta-analysis: application to a meta-analysis of 65 trials.
        Stat Med. 2002; 21: 2641-2652
        • Pignon J.-P..
        • Le Maître A.
        • Bourhis J.
        • On behalf of the MACH-NC Collaborative Group
        Meta-analyses of chemotherapy in head and neck cancer (MACH-NC): an update.
        Int J Radiat Oncol Biol Phys. 2007; 69: S112-S114
        • Schemper M.
        • Smith T.L.
        A note on quantifying follow-up in studies of failure time.
        Control Clin Trials. 1996; 17: 343-346
        • Yusuf S.
        • Peto R.
        • Lewis J.
        • Collins R.
        • Sleight T.
        Beta blockade during and after myocardial infarction: an overview of randomised clinical trials.
        Prog Cardiovasc Dis. 1985; 27: 335-371
        • Early Breast Cancer Trialists’ Collaborative Group
        Effects of radiotherapy and surgery in early breast cancer: an overview of randomized trials.
        N Engl J Med. 1995; 333: 1444-1455
        • Non-small Cell Lung Cancer Collaborative Group
        Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomized clinical trials.
        Br Med J. 1995; 311: 899-909
        • Higgins J.P.T.
        • Thompson S.G.
        Quantifying heterogeneity in a meta-analysis.
        Stat Med. 2002; 21: 1539-1558
        • Early Breast Cancer Trialists’ Collaborative Group
        Systemic treatment of early breast cancer by hormonal, cytotoxic or immune therapy: 133 randomised trials involving 31,000 recurrences and 24,000 death among 75,000 women.
        Lancet. 1992; 339: 1-15
        • Gabriele P.
        • Orecchia R.
        • Ragona R.
        • et al.
        A cooperative AIRO/Piemonte randomized clinical trial of carboplatin as an adjunct to radiotherapy in head and neck cancer.
        Radiat Oncol. 1994; 32: S93
        • Bhowmik K.T.
        • Safaya A.
        • Sharma R.
        • Suri K.
        • Bhatia J.S.
        • Das Nl.
        Concomitant chemoradiotherapy in advanced head and neck cancers: Safdarjang hospital experience.
        Radiat Oncol. 2001; 58: S16
        • Haselow R.E.
        • Warshaw M.G.
        • Oken M.M.
        • et al.
        Radiation alone versus radiation with weekly low dose cisplatinum in unrescetable cancer of the head and neck.
        in: Head and neck cancer. vol. II. BC Decker, Philadelphia1990: 279-281
        • Bourhis J.
        • Overgaard J.
        • Audry H.
        • et al.
        Hyperfractionated or accelerated radiotherapy in head and neck cancer: an individual patient data meta-analysis of 15 randomized trials.
        Lancet. 2006; 368: 843-854
      2. Available from: [last access on November 26, 2008].

        • Hitt R.
        • Lopez-Pousa A.
        • Martinez-Trufero J.
        • et al.
        Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally advanced head and neck cancer.
        J Clin Oncol. 2005; 23: 8636-8645
        • Posner M.R.
        • Hershock D.M.
        • Blajman C.R.
        • et al.
        Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer.
        N Engl J Med. 2007; 357: 1705-1715
        • Vermorken J.B.
        • Remenar E.
        • van Herpen C.
        • et al.
        Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer.
        N Engl J Med. 2007; 357: 1695-1704
        • Bonner J.A.
        • Harari P.M.
        • Giralt J.
        • et al.
        Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck.
        N Engl J Med. 2006; 354: 567-578