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


CONCLUSIONS
The benefit of concomitant chemotherapy was confirmed and was greater than the benefit of induction chemotherapy.
Pignon
Jean-Pierre
JP
Department of Biostatistics and Epidemiology, Institut Gustave-Roussy, Villejuif, France. jppignon@igr.fr
le Maître
Aurélie
A
Maillard
Emilie
E
Bourhis
Jean
J
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy; D003131:Combined Modality Therapy; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D015201:Meta-Analysis as Topic; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D000970:Antineoplastic Agents