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

Abstract Background 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 t...

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Published in:Radiotherapy and oncology 2009-07, Vol.92 (1), p.4-14
Main Authors: Pignon, Jean-Pierre, Maître, Aurélie le, Maillard, Emilie, Bourhis, Jean
Format: Article
Language:English
Subjects:
Antineoplastic Agents - therapeutic use
Carcinoma, Squamous Cell - drug therapy
Carcinoma, Squamous Cell - radiotherapy
Chemotherapy
Combined Modality Therapy
Head and neck cancer
Head and Neck Neoplasms - drug therapy
Head and Neck Neoplasms - radiotherapy
Hematology, Oncology and Palliative Medicine
Humans
Individual patient data
Meta-analysis
Meta-Analysis as Topic
Radiotherapy
Randomised clinical trials
Randomized Controlled Trials as Topic
Systematic review
Treatment Outcome
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creator Pignon, Jean-Pierre
Maître, Aurélie le
Maillard, Emilie
Bourhis, Jean
description Abstract Background 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. Methods 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. Results 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). Conclusion The benefit of concomitant chemotherapy was confirmed and was greater than the benefit of induction chemotherapy.
doi_str_mv 10.1016/j.radonc.2009.04.014
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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. Methods 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. Results 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 &lt; 0.0001) with an absolute benefit for chemotherapy of 4.5% at 5 years, and a significant interaction ( p &lt; 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 &lt; 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). Conclusion The benefit of concomitant chemotherapy was confirmed and was greater than the benefit of induction chemotherapy.</description><identifier>ISSN: 0167-8140</identifier><identifier>EISSN: 1879-0887</identifier><identifier>DOI: 10.1016/j.radonc.2009.04.014</identifier><identifier>PMID: 19446902</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Antineoplastic Agents - therapeutic use ; Carcinoma, Squamous Cell - drug therapy ; Carcinoma, Squamous Cell - radiotherapy ; Chemotherapy ; Combined Modality Therapy ; Head and neck cancer ; Head and Neck Neoplasms - drug therapy ; Head and Neck Neoplasms - radiotherapy ; Hematology, Oncology and Palliative Medicine ; Humans ; Individual patient data ; Meta-analysis ; Meta-Analysis as Topic ; Radiotherapy ; Randomised clinical trials ; Randomized Controlled Trials as Topic ; Systematic review ; Treatment Outcome</subject><ispartof>Radiotherapy and oncology, 2009-07, Vol.92 (1), p.4-14</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2009 Elsevier Ireland Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-28aca534320087ef84e772f80ea567f21a0bbefdddf8bfbeb5de2368cacb7b823</citedby><cites>FETCH-LOGICAL-c415t-28aca534320087ef84e772f80ea567f21a0bbefdddf8bfbeb5de2368cacb7b823</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19446902$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pignon, Jean-Pierre</creatorcontrib><creatorcontrib>Maître, Aurélie le</creatorcontrib><creatorcontrib>Maillard, Emilie</creatorcontrib><creatorcontrib>Bourhis, Jean</creatorcontrib><creatorcontrib>on behalf of the MACH-NC Collaborative Group</creatorcontrib><creatorcontrib>MACH-NC Collaborative Group</creatorcontrib><title>Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients</title><title>Radiotherapy and oncology</title><addtitle>Radiother Oncol</addtitle><description>Abstract Background 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. Methods 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. Results 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 &lt; 0.0001) with an absolute benefit for chemotherapy of 4.5% at 5 years, and a significant interaction ( p &lt; 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 &lt; 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). 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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. Methods 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. Results 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 &lt; 0.0001) with an absolute benefit for chemotherapy of 4.5% at 5 years, and a significant interaction ( p &lt; 0.0001) between chemotherapy timing (adjuvant, induction or concomitant) and treatment. 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subjects Antineoplastic Agents - therapeutic use
Carcinoma, Squamous Cell - drug therapy
Carcinoma, Squamous Cell - radiotherapy
Chemotherapy
Combined Modality Therapy
Head and neck cancer
Head and Neck Neoplasms - drug therapy
Head and Neck Neoplasms - radiotherapy
Hematology, Oncology and Palliative Medicine
Humans
Individual patient data
Meta-analysis
Meta-Analysis as Topic
Radiotherapy
Randomised clinical trials
Randomized Controlled Trials as Topic
Systematic review
Treatment Outcome
title Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients
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