Cochrane · intervention · CD006386

Interventions for the treatment of oral cavity and oropharyngeal cancer: chemotherapy

Parmar, A, Macluskey, M, Mc Goldrick, N, et al. · Cochrane Database of Systematic Reviews · 2021 · Cochrane Library

Oral Health Dental caries Oral medicine and oral cancer4 versionsAMSTAR 2: not assessed

Full textEvery question was extracted from the full review (methods and results), not only its Summary of Findings table.

Questions

18

current version

GRADE rated

7

No studies

2

Included studies

100

as reported

No studies 2 · 11.1%Ungraded 9 · 50%Very low 0 · 0%Low 3 · 16.7%Moderate 4 · 22.2%High 0 · 0%

Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.

Review question

Element	Planned (methods)	Found (results)
Population	Patients with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials included where >50% of participants have oral cavity/oropharyngeal cancer or separate data available	Oral cavity and oropharyngeal (and mixed head and neck, >50% oral/oropharyngeal) squamous cell carcinoma (n=100 trials; 18,813 participants)
Intervention	Chemotherapy (cytotoxic/antineoplastic drugs) by any mode of administration, as induction, concomitant or adjuvant treatment, +/- radiotherapy and/or surgery	Induction chemotherapy plus LRT (n=36); surgery + adjuvant treatment (n=varies); concurrent chemoradiotherapy (n=varies); head-to-head chemotherapy regimens (n=varies)
Comparison	Other chemotherapy / different regimen, timing or mode of administration; surgical combinations; radiotherapy combinations; no chemotherapy	Locoregional treatment alone (radiotherapy and/or surgery); observation/no chemotherapy; alternative chemotherapy regimen
Outcomes	Primary: Overall survival (time to death from any cause). Secondary: Disease-free survival (time to disease recurrence or death); Locoregional control (response to primary treatment)	Overall survival; Disease-free survival; Locoregional control
Study designs	Randomised controlled trials (minimum 6 months follow-up in PUB2 onwards)	Randomised controlled trials (RCT)
Timing	Not specified	Follow-up 3-8 years

Search date: 2021-09. Databases: Cochrane Oral Health's Trials Register; CENTRAL; MEDLINE (OVID); Embase (OVID); US National Institutes of Health Trials Registry (ClinicalTrials.gov); WHO ICTRP

Questions and results

Current version only

Induction chemotherapy plus locoregional treatment (radiotherapy and/or surgery) vs Locoregional treatment (radiotherapy and/or surgery) alone

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386.PUB4 (current) · 6 questions

Outcome	Effect	Evidence	Status / GRADE
Overall survival, induction platinum + 5-fluorouracil prior to surgery vs surgery alone same question in other reviews	HR 1.06 [0.71, 1.60] 200; 500; 700 per 1000 (low; medium; high risk population) vs 211; 520; 721 per 1000	1 study · 198 participants	Low Downgraded: imprecision
Disease-free survival, induction platinum + 5-fluorouracil prior to radiotherapy vs radiotherapy alone same question in other reviews	HR 0.78 [0.63, 0.97]	3 studies · 332 participants	Ungraded
Overall survival, induction cisplatin + 5-fluorouracil + docetaxel prior to concurrent chemoradiation (cisplatin) vs concurrent chemoradiation (cisplatin) same question in other reviews	HR 1.08 [0.80, 1.44] 200; 500; 700 per 1000 (low; medium; high risk population) vs 214; 527; 728 per 1000	3 studies · 760 participants	Low Downgraded: imprecision, inconsistency
Locoregional control, induction cisplatin + 5-fluorouracil + docetaxel prior to concurrent chemoradiation vs concurrent chemoradiation same question in other reviews	RR 0.80 [0.64, 0.99]	3 studies	Ungraded
Overall survival, induction platinum + 5-fluorouracil prior to radiotherapy vs radiotherapy alone same question in other reviews	HR 0.85 [0.70, 1.04] 200; 500; 700 per 1000 (low; medium; high risk population) vs 173; 445; 641 per 1000	5 studies · 7427 participants	Moderate Downgraded: inconsistency
Overall survival, induction cisplatin + 5-fluorouracil prior to concurrent chemoradiation (cisplatin) vs concurrent chemoradiation (cisplatin) same question in other reviews	HR 0.71 [0.37, 1.35] 200; 500; 700 per 1000 (low; medium; high risk population) vs 147; 389; 575 per 1000	2 studies · 389 participants	Low Downgraded: imprecision, inconsistency

Surgery +/- radiotherapy + (adjuvant) chemotherapy vs Surgery +/- radiotherapy alone (observation or adjuvant radiotherapy only)

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386.PUB4 (current) · 3 questions

Outcome	Effect	Evidence	Status / GRADE
Overall survival, adjuvant chemotherapy vs observation alone following surgery same question in other reviews	HR 0.95 [0.73, 1.22] 200; 500; 700 per 1000 (low; medium; high risk population) vs 191; 482; 681 per 1000	5 studies · 353 participants	Moderate Downgraded: imprecision
Disease-free survival, adjuvant concurrent chemoradiation vs adjuvant radiotherapy (pooled) same question in other reviews	HR 0.84 [0.72, 0.97]	4 studies	Ungraded
Overall survival, adjuvant concurrent chemoradiation vs adjuvant radiotherapy same question in other reviews	HR 0.84 [0.72, 0.98] 200; 500; 700 per 1000 (low; medium; high risk population) vs 171; 441; 636 per 1000	4 studies · 1097 participants	Moderate Downgraded: inconsistency

Concomitant (concurrent) chemoradiotherapy vs Radiotherapy alone (non-resectable tumours)

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386.PUB4 (current) · 3 questions

Outcome	Effect	Evidence	Status / GRADE
Locoregional control, concurrent chemoradiotherapy (platinum + 5-fluorouracil) vs radiotherapy alone (pooled) same question in other reviews	RR 0.75 [0.61, 0.93]	3 studies	Ungraded
Disease-free survival, concurrent chemoradiotherapy vs radiotherapy alone (pooled) same question in other reviews	HR 0.74 [0.67, 0.80]	13 studies	Ungraded
Overall survival, concurrent chemoradiotherapy vs radiotherapy alone (pooled) same question in other reviews	HR 0.74 [0.67, 0.83] 200; 500; 700 per 1000 (low; medium; high risk population) vs 156; 410; 599 per 1000	24 studies · 2852 participants	Moderate Downgraded: inconsistency

Chemotherapy regimen A (+/- locoregional treatment) vs Chemotherapy regimen B (+/- locoregional treatment)

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386.PUB4 (current) · 3 questions

Outcome	Effect	Evidence	Status / GRADE
Overall survival, chemotherapy regimen A vs regimen B same question in other reviews	Eight of 11 induction-before-radiotherapy studies reported overall survival; not pooled (heterogeneity). Only Vermorken 2007 significant: cisplatin+5-FU+docetaxel induction HR 0.73 (95% CI 0.57 to 0.93, P = 0.01).…	8 studies	Ungraded
Disease-free survival, chemotherapy regimen A vs regimen B same question in other reviews	Induction cisplatin+5-FU+docetaxel vs cisplatin+5-FU: disease-free survival HR 0.72 (95% CI 0.57 to 0.91, P = 0.006; Vermorken 2007). Prior to concurrent chemoradiation: Posner 2007 HR 0.71 (0.56 to 0.90, P = 0.005).…	2 studies	Ungraded
Locoregional control, chemotherapy regimen A vs regimen B same question in other reviews	Locoregional control reported in 12 studies; not pooled. Olasz 2000 RR 0.50 (0.26 to 0.96); Prevost 2005 RR 1.48 (1.04 to 2.11); Molinari 1982 RR 0.35 (0.19 to 0.66).	12 studies	Ungraded

Chemotherapy (any regimen; added to, or compared with, locoregional treatment) vs Locoregional treatment and/or an alternative chemotherapy regimen

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386.PUB4 (current) · 2 questions

Outcome	Effect	Evidence	Status / GRADE
Quality of life same question in other reviews	Quality of life was a planned (protocol) outcome but no included trial provided usable quality-of-life data; the protocol was modified to report only survival/response outcomes.	0 studies	No studies
Toxicity / adverse effects (harms) of chemotherapy same question in other reviews	Harms/toxicity were planned but very little quantitative data suitable for analysis were found; toxicity reported narratively and not quantified or GRADE-rated.	NR	Ungraded

Chemotherapy vs Placebo

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386.PUB4 (current) · 1 question

Outcome	Effect	Evidence	Status / GRADE
Outcome NR same question in other reviews	Types of studies: it was anticipated that there would be no studies comparing chemotherapy with placebo (none were identified).	0 studies	No studies

Induction chemotherapy plus locoregional treatment (radiotherapy and/or surgery) vs Locoregional treatment (radiotherapy and/or surgery) alone

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386.PUB3 · 6 questions

Outcome	Effect	Evidence	Status / GRADE
Locoregional recurrence, induction chemotherapy plus LRT vs LRT alone (Licitra 2003)	Licitra 2003: locoregional recurrence - no statistically significant difference.	1 study	Ungraded
Disease-free survival, induction chemotherapy plus LRT vs LRT alone (pooled)	HR 0.78 [0.67, 0.90]	8 studies	Ungraded
Overall survival (total mortality), induction chemotherapy plus LRT vs LRT alone (all studies pooled)	HR 0.92 [0.84, 1.00] 200; 500; 700 per 1000 (low; medium; high risk population) vs 186; 471; 670 per 1000	25 studies · 4051 participants	Very low Downgraded: risk of bias, indirectness
Overall survival (total mortality), induction chemotherapy plus LRT vs LRT alone (low risk-of-bias studies sensitivity analysis)	HR 0.80 [0.67, 0.97] 200; 500; 700 per 1000 (low; medium; high risk population) vs 163; 426; 618 per 1000	4 studies · 968 participants	Moderate Downgraded: indirectness
Progression-free survival, induction chemotherapy plus LRT vs LRT alone (pooled)	HR 0.80 [0.64, 1.00]	2 studies	Ungraded
Disease-free survival at 5 years, induction chemotherapy plus LRT vs LRT alone (Licitra 2003)	Licitra 2003: disease free survival at 5 years - no statistically significant difference.	1 study	Ungraded

Surgery +/- radiotherapy + (adjuvant) chemotherapy vs Surgery +/- radiotherapy alone (observation or adjuvant radiotherapy only)

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386.PUB3 · 7 questions

Outcome	Effect	Evidence	Status / GRADE
Overall survival (total mortality), surgery +/- RT + adjuvant chemotherapy vs surgery +/- RT alone (low risk-of-bias studies sensitivity)	HR 0.88 [0.74, 1.05] 200; 500; 700 per 1000 (low; medium; high risk population) vs 178; 457; 653 per 1000	4 studies · 758 participants	Moderate Downgraded: indirectness
Disease-free survival, surgery +/- RT + adjuvant chemotherapy vs surgery +/- RT alone (pooled)	HR 0.89 [0.78, 1.01]	8 studies	Ungraded
Locoregional recurrence, adjuvant cisplatin chemoradiotherapy vs post-surgery radiotherapy alone (Cooper 2004)	HR 0.61 [0.41, 0.91]	1 study	Ungraded
Overall survival (total mortality), surgery +/- RT + adjuvant chemotherapy vs surgery +/- RT alone (all studies pooled)	HR 0.88 [0.79, 0.99] 200; 500; 700 per 1000 (low; medium; high risk population) vs 178; 457; 653 per 1000	10 studies · 2017 participants	Low Downgraded: risk of bias, indirectness
Overall survival, adjuvant concomitant chemoradiotherapy vs post-surgery radiotherapy alone	HR 0.84 [0.72, 0.98]	4 studies	Ungraded
Progression-free survival, adjuvant cisplatin chemoradiotherapy vs post-surgery radiotherapy alone (Bernier 2004)	HR 0.75 [0.57, 0.99]	1 study	Ungraded
Overall survival, post-surgery chemotherapy vs surgery alone (no radiotherapy)	HR 0.84 [0.50, 1.39]	2 studies	Ungraded

Concomitant (concurrent) chemoradiotherapy vs Radiotherapy alone (non-resectable tumours)

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386.PUB3 · 6 questions

Outcome	Effect	Evidence	Status / GRADE
Locoregional control (complete response to treatment), concomitant chemoradiotherapy vs radiotherapy alone	Four trials reported complete response to treatment; due to substantial heterogeneity, data were not pooled.	4 studies	Ungraded
Progression-free survival, concomitant/alternating chemoradiotherapy vs radiotherapy alone (pooled)	HR 0.77 [0.67, 0.89]	6 studies	Ungraded
Locoregional control, concomitant chemoradiotherapy vs radiotherapy alone (pooled)	HR 0.73 [0.64, 0.82]	7 studies	Ungraded
Disease-free survival, concomitant chemoradiotherapy vs radiotherapy alone (pooled)	HR 0.77 [0.70, 0.84]	8 studies	Ungraded
Overall survival (total mortality), concomitant/alternating chemoradiotherapy vs radiotherapy alone (low risk-of-bias studies sensitivity)	HR 0.87 [0.79, 0.95] 200; 500; 700 per 1000 (low; medium; high risk population) vs 176; 453; 649 per 1000	9 studies · 2266 participants	Moderate Downgraded: indirectness
Overall survival (total mortality), concomitant/alternating chemoradiotherapy vs radiotherapy alone (all studies pooled)	HR 0.78 [0.73, 0.83] 200; 500; 700 per 1000 (low; medium; high risk population) vs 160; 418; 609 per 1000	26 studies · 4734 participants	Low Downgraded: risk of bias, indirectness

Chemotherapy regimen A (+/- locoregional treatment) vs Chemotherapy regimen B (+/- locoregional treatment)

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386.PUB3 · 4 questions

Outcome	Effect	Evidence	Status / GRADE
Progression-free survival, chemotherapy regimen A vs regimen B	7 trials reported progression free survival; not pooled (heterogeneous regimens).	7 studies	Ungraded
Disease-free survival, chemotherapy regimen A vs regimen B	7 trials reported disease free survival; not pooled (heterogeneous regimens).	7 studies	Ungraded
Overall survival (total mortality), chemotherapy regimen A vs regimen B	20 trials reported total mortality across heterogeneous head-to-head chemotherapy comparisons; not pooled.	20 studies	Ungraded
Locoregional control, chemotherapy regimen A vs regimen B	Several trials reported locoregional control/recurrence; not pooled (heterogeneous regimens).	NR	Ungraded

Chemotherapy (any regimen; added to, or compared with, locoregional treatment) vs Locoregional treatment and/or an alternative chemotherapy regimen

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386.PUB3 · 2 questions

Outcome	Effect	Evidence	Status / GRADE
Quality of life	Quality of life was a planned (protocol) outcome but no included trial provided usable quality-of-life data; the protocol was modified to report only survival/response outcomes.	0 studies	No studies
Toxicity / adverse effects (harms) of chemotherapy	Harms/toxicity were planned but very little quantitative data suitable for analysis were found; toxicity reported narratively and not quantified or GRADE-rated.	NR	Ungraded

Chemotherapy vs Placebo

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386.PUB3 · 1 question

Outcome	Effect	Evidence	Status / GRADE
Outcome NR	Types of studies: it was anticipated that there would be no studies comparing chemotherapy with placebo (none were identified).	0 studies	No studies

Induction chemotherapy plus locoregional treatment (radiotherapy and/or surgery) vs Locoregional treatment (radiotherapy and/or surgery) alone

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386.PUB2 · 5 questions

Outcome	Effect	Evidence	Status / GRADE
Progression-free survival, induction chemotherapy plus LRT vs LRT alone (pooled)	HR 0.80 [0.64, 1.00]	2 studies	Ungraded
Overall survival (total mortality), induction chemotherapy plus LRT vs LRT alone (all regimens pooled)	HR 0.92 [0.84, 1.00]	25 studies	Ungraded
Disease-free survival at 5 years, induction chemotherapy plus LRT vs LRT alone (Licitra 2003)	Licitra 2003 reported disease free survival at 5 years (Comparison 1.4.1) - no statistically significant difference between groups.	1 study	Ungraded
Disease-free survival, induction chemotherapy plus LRT vs LRT alone (pooled)	HR 0.78 [0.67, 0.90]	8 studies	Ungraded
Locoregional recurrence, induction chemotherapy plus LRT vs LRT alone (Licitra 2003)	Licitra 2003 reported locoregional recurrence (Comparison 1.5.1) - no statistically significant difference between groups.	1 study	Ungraded

Surgery +/- radiotherapy + (adjuvant) chemotherapy vs Surgery +/- radiotherapy alone (observation or adjuvant radiotherapy only)

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386.PUB2 · 6 questions

Outcome	Effect	Evidence	Status / GRADE
Overall survival, adjuvant concomitant chemoradiotherapy vs post-surgery radiotherapy alone	HR 0.84 [0.72, 0.98]	4 studies	Ungraded
Progression-free survival, adjuvant cisplatin chemoradiotherapy vs post-surgery radiotherapy alone (Bernier 2004)	HR 0.75 [0.57, 0.99]	1 study	Ungraded
Disease-free survival, surgery +/- RT + adjuvant chemotherapy vs surgery +/- RT alone (pooled)	HR 0.87 [0.73, 1.04]	3 studies	Ungraded
Locoregional recurrence, adjuvant cisplatin chemoradiotherapy vs post-surgery radiotherapy alone (Cooper 2004)	HR 0.61 [0.41, 0.91]	1 study	Ungraded
Overall survival, post-surgery chemotherapy vs surgery alone (no radiotherapy)	HR 0.84 [0.50, 1.39]	2 studies	Ungraded
Overall survival (total mortality), surgery +/- RT + adjuvant chemotherapy vs surgery +/- RT alone (all regimens pooled)	HR 0.88 [0.79, 0.99]	10 studies	Ungraded

Concomitant (concurrent) chemoradiotherapy vs Radiotherapy alone (non-resectable tumours)

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386.PUB2 · 5 questions

Outcome	Effect	Evidence	Status / GRADE
Disease-free survival, concomitant chemoradiotherapy vs radiotherapy alone (pooled)	HR 0.77 [0.70, 0.84]	8 studies	Ungraded
Locoregional control, concomitant chemoradiotherapy vs radiotherapy alone (pooled)	HR 0.73 [0.64, 0.82]	7 studies	Ungraded
Progression-free survival, concomitant chemoradiotherapy vs radiotherapy alone (pooled)	HR 0.77 [0.67, 0.89]	4 studies	Ungraded
Locoregional control (complete response to treatment), concomitant chemoradiotherapy vs radiotherapy alone	Four trials of an antitumour antibiotic reported complete response to treatment; due to substantial clinical and statistical heterogeneity, data were not pooled.	4 studies	Ungraded
Overall survival (total mortality), concomitant/alternating chemoradiotherapy vs radiotherapy alone (pooled)	HR 0.78 [0.73, 0.83]	27 studies	Ungraded

Chemotherapy regimen A (+/- locoregional treatment) vs Chemotherapy regimen B (+/- locoregional treatment)

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386.PUB2 · 4 questions

Outcome	Effect	Evidence	Status / GRADE
Progression-free survival, chemotherapy regimen A vs regimen B	7 trials reported progression free survival for head-to-head chemotherapy comparisons; not pooled (heterogeneous regimens).	7 studies	Ungraded
Disease-free survival, chemotherapy regimen A vs regimen B	7 trials reported disease free survival for head-to-head chemotherapy comparisons; not pooled (heterogeneous regimens).	7 studies	Ungraded
Locoregional control, chemotherapy regimen A vs regimen B	Several trials reported locoregional control / recurrence for head-to-head chemotherapy comparisons; not pooled (heterogeneous regimens).	NR	Ungraded
Overall survival (total mortality), chemotherapy regimen A vs regimen B	20 trials reported total mortality across heterogeneous head-to-head chemotherapy comparisons; regimens too heterogeneous to pool into a single estimate.	20 studies	Ungraded

Chemotherapy (any regimen; added to, or compared with, locoregional treatment) vs Locoregional treatment and/or an alternative chemotherapy regimen

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386.PUB2 · 2 questions

Outcome	Effect	Evidence	Status / GRADE
Toxicity / adverse effects (harms) of chemotherapy	Harms/toxicity were planned but very little quantitative data suitable for analysis were found; toxicity reported narratively and not quantified or GRADE-rated.	NR	Ungraded
Quality of life	Quality of life was a planned (protocol) outcome but no included trial provided usable quality-of-life data; the protocol was modified to report only survival/response outcomes.	0 studies	No studies

Chemotherapy vs Placebo

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386.PUB2 · 1 question

Outcome	Effect	Evidence	Status / GRADE
Outcome NR	Types of studies: it was anticipated that there would be no studies comparing chemotherapy with placebo (none were identified).	0 studies	No studies

Chemotherapy (any regimen; added to, or compared with, locoregional treatment) vs Locoregional treatment and/or an alternative chemotherapy regimen

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386 · 4 questions

Outcome	Effect	Evidence	Status / GRADE
Disease-free survival or time to recurrence	Protocol (Types of outcome measures, primary): Disease-free survival or time to recurrence. Protocol; no included studies.	0 studies	No studies
Total mortality (overall survival)	Protocol (Types of outcome measures, primary): Total mortality (disease related mortality will also be studied if possible). Protocol; no included studies.	0 studies	No studies
Quality of life	Protocol (Types of outcome measures, primary): Quality of life (using any appropriate scales, for example those produced by the University of Washington and the EORTC). Protocol; no included studies.	0 studies	No studies
Toxicity / adverse effects (harms) of chemotherapy	Protocol (Types of outcome measures, secondary): Harms associated with treatment (for example nerve damage, nutritional problems); complications of treatment. Protocol; no included studies.	0 studies	No studies

Chemotherapy vs Placebo

Population: People receiving curative-intent treatment for oral cavity and oropharyngeal (squamous cell) cancer

CD006386 · 1 question

Outcome	Effect	Evidence	Status / GRADE
Outcome NR	Protocol (Types of studies): 'It is anticipated that there will be no studies comparing any of the treatment modalities with placebo (although if there are such studies they will be included), therefore randomised…	0 studies	No studies