TY - JOUR
T1 - Interventions for the treatment of oral cavity and oropharyngeal cancer
T2 - chemotherapy
AU - Parmar, Ambika
AU - Macluskey, Michaelina
AU - Mc Goldrick, Niall
AU - Conway, David I.
AU - Glenny, Anne Marie
AU - Clarkson, Janet E.
AU - Worthington, Helen V.
AU - Chan, Kelvin K. W.
N1 - Funding Information:
For this update, we would like to thank Laura MacDonald, Anne Littlewood, Philip Riley, Martin McCabe, Tanya Walsh, Jennifer Hilgart, Soodabeh Behboodi and Anne Lethaby. We would like to acknowledge the work of the CSROC (Cochrane Systematic Reviews in Oral Cancer) Expert Panel who played a substantial role in the design of the original protocols for this series of reviews and provided comments and advice on the early drafts. The CSROC Expert Panel comprised Bertrand Baujat, Gerry Humphris, Iain Hutchison, Jean-Pierre Pignon, Gerry Robertson, Simon Rogers, Jatin Shah, Nick Slevin, Phil Sloan, David Soutar, Erich Sturgis, Jan Vermorken, Steve Wardell, Saman Warnakulasuriya and Keith Webster. We would like to thank the following individuals for their contributions to protocol development, search strategy development and conduct, full-text retrieval, statistical input, as well as expert opinion: Emma Tavender, Sylvia Bickley, Anne Littlewood, Phil Riley, Brian Bonner, May Wong, Chris O'Brien, Susan Furness, Sue Pavitt and Richard Oliver. Thanks to the following for their translation of published papers into English. Toru Naito - translated Tsukuda 1994, Yoshino 1991 and Yoshino 1994 from Japanese Anette Bluemle - translated Muncker 2000, Von Heyden 1982, Von Heyden 1984, Von Heyden 1984, and Bitter 1979 from German J-H Vergnes translated Haddad 1996 from French Prof V Vlassov and Dr Oleg Borisenko translated Gladkov 2007 from Russian Daniel Bereczki translated Olasz 2000 from Hungarian Luisa Fernandez-Mauleffinch translated Giglio 1997 and Segura 2002 from Spanish Dr Nicoletta Bobola translated Buffoli 1992 from Italian Toru Naito - translated Tsukuda 1994, Yoshino 1991 and Yoshino 1994 from Japanese Anette Bluemle - translated Muncker 2000, Von Heyden 1982, Von Heyden 1984, Von Heyden 1984, and Bitter 1979 from German J-H Vergnes translated Haddad 1996 from French Prof V Vlassov and Dr Oleg Borisenko translated Gladkov 2007 from Russian Daniel Bereczki translated Olasz 2000 from Hungarian Luisa Fernandez-Mauleffinch translated Giglio 1997 and Segura 2002 from Spanish Dr Nicoletta Bobola translated Buffoli 1992 from Italian
Funding Information:
Funding source: government. Grants-in-Aid for Scientific Research (B)10557087, 11470190, and 11877152 from the Japanese Ministry of Education, Science, and Culture
Funding Information:
Funding source: grant from Department of Science & Tecnology, Government of India, under Project number 1/37/82 - STP - III Inclusion: T3-T4 histologically confirmed squamous cell carcinoma of buccal mucosa with or without cervical node metastases, except for those with fixed N3 masses outside submandibular region. Those with external fungation, muscle invasion were eligible.
Funding Information:
Funding source: grants from FNLCC & 'Ligue Departmentate de L'Aube'
Funding Information:
Funding source: supported by the German Cancer Aid
Publisher Copyright:
Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
PY - 2021/12/20
Y1 - 2021/12/20
N2 - Background: Oral cavity and oropharyngeal cancers are the most common cancers arising in the head and neck. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients. This review updates one last published in 2011.Objectives: To determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal squamous cell carcinoma results in improved overall survival, improved disease-free survival and/or improved locoregional control, when incorporated as either induction therapy given prior to locoregional treatment (i.e. radiotherapy or surgery), concurrent with radiotherapy or in the adjuvant (i.e. after locoregional treatment with radiotherapy or surgery) setting.Search methods: An information specialist searched 4 bibliographic databases up to 15 September 2021 and used additional search methods to identify published, unpublished and ongoing studies.Selection criteria: We included randomised controlled trials (RCTs) where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and that evaluated the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration.Data collection and analysis: For this update, we assessed the new included trials for their risk of bias and at least two authors extracted data from them. Our primary outcome was overall survival (time to death from any cause). Secondary outcomes were disease-free survival (time to disease recurrence or death from any cause) and locoregional control (response to primary treatment). We contacted trial authors for additional information or clarification when necessary.Main results: We included 100 studies with 18,813 participants. None of the included trials were at low risk of bias.For induction chemotherapy, we reported the results for contemporary regimens that will be of interest to clinicians and people being treated for oral cavity and oropharyngeal cancers. Overall, there is insufficient evidence to clearly demonstrate a survival benefit from induction chemotherapy with platinum plus 5-fluorouracil prior to radiotherapy (hazard ratio (HR) for death 0.85, 95% confidence interval (CI) 0.70 to 1.04, P = 0.11; 7427 participants, 5 studies; moderate-certainty evidence), prior to surgery (HR for death 1.06, 95% CI 0.71 to 1.60, P = 0.77; 198 participants, 1 study; low-certainty evidence) or prior to concurrent chemoradiation (CRT) with cisplatin (HR for death 0.71, 95% CI 0.37 to 1.35, P = 0.30; 389 participants, 2 studies; low-certainty evidence). There is insufficient evidence to support the use of an induction chemotherapy regimen with cisplatin plus 5-fluorouracil plus docetaxel prior to CRT with cisplatin (HR for death 1.08, 95% CI 0.80 to 1.44, P = 0.63; 760 participants, 3 studies; low-certainty evidence).There is insufficient evidence to support the use of adjuvant chemotherapy over observation only following surgery (HR for death 0.95, 95% CI 0.73 to 1.22, P = 0.67; 353 participants, 5 studies; moderate-certainty evidence). Among studies that compared post-surgical adjuvant CRT, as compared to post-surgical RT, adjuvant CRT showed a survival benefit (HR 0.84, 95% CI 0.72 to 0.98, P = 0.03; 1097 participants, 4 studies; moderate-certainty evidence).Primary treatment with CRT, as compared to radiotherapy alone, was associated with a reduction in the risk of death (HR for death 0.74, 95% CI 0.67 to 0.83, P < 0.00001; 2852 participants, 24 studies; moderate-certainty evidence).Authors' conclusions: The results of this review demonstrate that chemotherapy in the curative-intent treatment of oral cavity and oropharyngeal cancers only seems to be of benefit when used in specific circumstances together with locoregional treatment. The evidence does not show a clear survival benefit from the use of induction chemotherapy prior to radiotherapy, surgery or CRT. Adjuvant CRT reduces the risk of death by 16%, as compared to radiotherapy alone. Concurrent chemoradiation as compared to radiation alone is associated with a greater than 20% improvement in overall survival; however, additional research is required to inform how the specific chemotherapy regimen may influence this benefit.
AB - Background: Oral cavity and oropharyngeal cancers are the most common cancers arising in the head and neck. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients. This review updates one last published in 2011.Objectives: To determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal squamous cell carcinoma results in improved overall survival, improved disease-free survival and/or improved locoregional control, when incorporated as either induction therapy given prior to locoregional treatment (i.e. radiotherapy or surgery), concurrent with radiotherapy or in the adjuvant (i.e. after locoregional treatment with radiotherapy or surgery) setting.Search methods: An information specialist searched 4 bibliographic databases up to 15 September 2021 and used additional search methods to identify published, unpublished and ongoing studies.Selection criteria: We included randomised controlled trials (RCTs) where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and that evaluated the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration.Data collection and analysis: For this update, we assessed the new included trials for their risk of bias and at least two authors extracted data from them. Our primary outcome was overall survival (time to death from any cause). Secondary outcomes were disease-free survival (time to disease recurrence or death from any cause) and locoregional control (response to primary treatment). We contacted trial authors for additional information or clarification when necessary.Main results: We included 100 studies with 18,813 participants. None of the included trials were at low risk of bias.For induction chemotherapy, we reported the results for contemporary regimens that will be of interest to clinicians and people being treated for oral cavity and oropharyngeal cancers. Overall, there is insufficient evidence to clearly demonstrate a survival benefit from induction chemotherapy with platinum plus 5-fluorouracil prior to radiotherapy (hazard ratio (HR) for death 0.85, 95% confidence interval (CI) 0.70 to 1.04, P = 0.11; 7427 participants, 5 studies; moderate-certainty evidence), prior to surgery (HR for death 1.06, 95% CI 0.71 to 1.60, P = 0.77; 198 participants, 1 study; low-certainty evidence) or prior to concurrent chemoradiation (CRT) with cisplatin (HR for death 0.71, 95% CI 0.37 to 1.35, P = 0.30; 389 participants, 2 studies; low-certainty evidence). There is insufficient evidence to support the use of an induction chemotherapy regimen with cisplatin plus 5-fluorouracil plus docetaxel prior to CRT with cisplatin (HR for death 1.08, 95% CI 0.80 to 1.44, P = 0.63; 760 participants, 3 studies; low-certainty evidence).There is insufficient evidence to support the use of adjuvant chemotherapy over observation only following surgery (HR for death 0.95, 95% CI 0.73 to 1.22, P = 0.67; 353 participants, 5 studies; moderate-certainty evidence). Among studies that compared post-surgical adjuvant CRT, as compared to post-surgical RT, adjuvant CRT showed a survival benefit (HR 0.84, 95% CI 0.72 to 0.98, P = 0.03; 1097 participants, 4 studies; moderate-certainty evidence).Primary treatment with CRT, as compared to radiotherapy alone, was associated with a reduction in the risk of death (HR for death 0.74, 95% CI 0.67 to 0.83, P < 0.00001; 2852 participants, 24 studies; moderate-certainty evidence).Authors' conclusions: The results of this review demonstrate that chemotherapy in the curative-intent treatment of oral cavity and oropharyngeal cancers only seems to be of benefit when used in specific circumstances together with locoregional treatment. The evidence does not show a clear survival benefit from the use of induction chemotherapy prior to radiotherapy, surgery or CRT. Adjuvant CRT reduces the risk of death by 16%, as compared to radiotherapy alone. Concurrent chemoradiation as compared to radiation alone is associated with a greater than 20% improvement in overall survival; however, additional research is required to inform how the specific chemotherapy regimen may influence this benefit.
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Carcinoma, Squamous Cell
KW - Combined Modality Therapy
KW - Mouth Neoplasms
KW - Oropharyngeal Neoplasms
KW - Randomized Controlled Trails as Topic
KW - Remission Induction
KW - Survival Analysis
UR - http://www.scopus.com/inward/record.url?scp=85121704638&partnerID=8YFLogxK
U2 - 10.1002/14651858.CD006386.pub4
DO - 10.1002/14651858.CD006386.pub4
M3 - Review article
C2 - 34929047
AN - SCOPUS:85121704638
SN - 1465-1858
VL - 2021
JO - Cochrane Database of Systematic Reviews
JF - Cochrane Database of Systematic Reviews
IS - 12
M1 - CD006386
ER -