What do systematic reviews say?

Topical bleomycin vs placebo or no treatment

It is very uncertain whether topical bleomycin changes improvement of histological features (not improved) compared with placebo or no treatment (very low certainty).

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes

  3 months
  RR 0.49 [0.22, 1.10]
  1 study · 21 participants
  Very low

Herbal extracts (tea components; Chinese herbal mixture; freeze-dried black raspberry gel) vs placebo or no treatment

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes

  up to 3 months
  SoF 4, Safety of the intervention up to 3 months: '3 studies measured adverse effects: green tea extract capsules caused high frequency (93%) of adverse effects of varying severity in 1 study; the mixed tea study did…
  3 studies
  GRADE not reported

Removal of predisposing habits (e.g. tobacco/alcohol cessation) vs Placebo or no treatment

The review found no eligible studies for this question.

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes
  '...nor did we identify any RCTs of risk factor cessation.' Removal of predisposing habits (e.g. smoking cessation) was a planned intervention; no eligible RCT found.
  Studies not reported
  No studies found

Vitamin A or retinoids (systemic or topical; incl. 13-cis-retinoic acid, acitretin) vs placebo or no treatment

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes

  4 to 12 months
  SoF 1, Safety of the intervention at 4 to 12 months: '3 studies (1 each evaluating topical acitretin, topical 13-cis-retinoic acid, 200,000 IU per week of vitamin A) found no adverse effects. Systemic 13-cis-retinoic…
  4 studies
  GRADE not reported

Bowman-Birk inhibitor vs placebo or no treatment

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes

  up to 6 months
  SoF 6, Safety of the intervention up to 6 months: 'Trial authors reported that there were no significant adverse effects. 33 participants in the intervention group reported 75 adverse effects. 25 participants in the…
  1 study
  GRADE not reported

Non-specific immunotherapy (recombinant interleukin-2 or BCG cell wall preparation) plus standard therapy vs Standard therapy alone (radiotherapy or chemoradiotherapy)

Non-specific immunotherapy (recombinant interleukin-2 or BCG cell… showed no clear difference in adverse effects compared with standard therapy alone; GRADE not reported.

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Moderate to severe chills (BCG-CWP, all grades)
  RR 11.00 [0.67, 179.29]
  1 study · 24 participants
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Nausea/vomiting (rIL-2, grades >=3)
  RR 3.40 [0.15, 77.34]
  1 study · 30 participants
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Stomatitis (rIL-2, all grades)
  RR 1.47 [0.75, 2.90]
  1 study · 30 participants
  GRADE not reported

Tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy)

Tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus… led to higher adverse effects compared with standard therapy alone (radiotherapy or chemoradiotherapy); GRADE not reported.

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  40 to 60 months · Skin toxicity (lapatinib, all grades)
  RR 2.02 [1.23, 3.32]
  1 study · 67 participants
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  40 to 60 months · Gastrointestinal complaints (gefitinib, all grades)
  RR 1.04 [0.98, 1.11]
  1 study · 226 participants
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  40 to 60 months · Gastrointestinal complaints (lapatinib, all grades)
  RR 15.53 [2.18, 110.55]
  1 study · 67 participants
  GRADE not reported

EGFR monoclonal antibody (cetuximab or nimotuzumab) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy)

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Mucositis (all grades)
  Mucositis all grades: not estimable due to high heterogeneity (P=0.0009; I2=86%) between subgroups (cetuximab; nimotuzumab) and within cetuximab (I2=93%); 1417 participants, 3 studies. Table 3, row 1.6 (Ang 2014;…
  3 studies · 1417 participants
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Skin toxicity/acneiform rash (cetuximab, all grades)
  RR 6.56 [5.35, 8.03]
  2 studies · 1311 participants
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Xerostomia (grades >=3)
  RR 1.36 [0.80, 2.31]
  2 studies · 1311 participants
  GRADE not reported

Non-specific immunotherapy (recombinant interleukin-2 or BCG cell wall preparation) plus standard therapy vs Standard therapy alone (radiotherapy or chemoradiotherapy)

It is very uncertain whether non-specific immunotherapy (recombinant interleukin-2 or BCG cell… changes disease-free survival compared with standard therapy alone (very low certainty).

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Recombinant interleukin-2 + surgery (De Stefani 2002)
  HR 0.66 [0.43, 1.02]
  1 study · 201 participants
  Very low

EGFR monoclonal antibody (cetuximab or nimotuzumab) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy)

EGFR monoclonal antibody (cetuximab or nimotuzumab) plus standard… showed no clear difference in progression-free survival compared with standard therapy alone (radiotherapy or chemoradiotherapy); GRADE not reported.

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Monoclonal antibody + chemoradiotherapy vs chemoradiotherapy alone
  HR 1.08 [0.89, 1.32]
  1 study · 891 participants
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Monoclonal antibody + radiotherapy vs radiotherapy alone
  HR 0.70 [0.54, 0.91]
  1 study · 424 participants
  GRADE not reported

Tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy)

It is very uncertain whether tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus… changes progression-free survival compared with standard therapy alone (radiotherapy or chemoradiotherapy) (very low certainty).

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  40 to 60 months
  HR 0.80 [0.51, 1.28]
  2 studies · 271 participants
  Very low

EGFR monoclonal antibody (cetuximab or nimotuzumab) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy)

The review found no eligible studies for this question.

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months
  No included studies addressed participant satisfaction (review-wide gap).
  0 studies
  No studies found

EGFR monoclonal antibody (cetuximab or nimotuzumab) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy)

The review found no eligible studies for this question.

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months
  No included studies addressed direct and indirect costs to participants and health services (review-wide gap).
  0 studies
  No studies found

EGFR monoclonal antibody (cetuximab or nimotuzumab) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy)

EGFR monoclonal antibody (cetuximab or nimotuzumab) plus standard… probably leads to lower overall survival compared with standard therapy alone (radiotherapy or chemoradiotherapy) (moderate certainty).

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months
  HR 0.82 [0.69, 0.97]
  3 studies · 1421 participants
  Moderate

Non-specific immunotherapy (recombinant interleukin-2 or BCG cell wall preparation) plus standard therapy vs Standard therapy alone (radiotherapy or chemoradiotherapy)

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · BCG cell wall preparation + surgery (Bier 1981)
  BCG-CWP + surgery versus surgery alone: 3-year overall survival 10/10 vs 9/10; too few participants to calculate a hazard ratio (Bier 1981, 24 participants).
  1 study · 24 participants
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Recombinant interleukin-2 + surgery (De Stefani 2002)
  HR 0.52 [0.31, 0.87]
  1 study · 201 participants
  Very low

Tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy)

It is very uncertain whether tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus… changes overall survival compared with standard therapy alone (radiotherapy or chemoradiotherapy) (very low certainty).

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  40 to 60 months
  HR 0.99 [0.62, 1.57]
  2 studies · 271 participants
  Very low

Tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy)

It is very uncertain whether tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus… changes disease-free survival compared with standard therapy alone (radiotherapy or chemoradiotherapy) (very low certainty).

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  40 to 60 months · Gefitinib + radiotherapy (oral cavity)
  HR 1.51 [0.61, 3.71]
  1 study · 60 participants
  Very low

Tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy)

It is very uncertain whether tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus… changes locoregional control compared with standard therapy alone (radiotherapy or chemoradiotherapy) (very low certainty).

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  40 to 60 months
  HR 0.89 [0.53, 1.49]
  2 studies · 271 participants
  Very low

EGFR monoclonal antibody (cetuximab or nimotuzumab) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy)

EGFR monoclonal antibody (cetuximab or nimotuzumab) plus standard… probably leads to lower locoregional control compared with standard therapy alone (radiotherapy or chemoradiotherapy) (moderate certainty).

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months
  HR 0.68 [0.52, 0.89]
  1 study · 424 participants
  Moderate

Non-specific immunotherapy (recombinant interleukin-2 or BCG cell wall preparation) plus standard therapy vs Standard therapy alone (radiotherapy or chemoradiotherapy)

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Recombinant interleukin-2 + neoadjuvant chemotherapy (Mantovani 1998), tumour response
  Response to treatment (Mantovani 1998; neoadjuvant chemotherapy + rIL-2 vs chemotherapy alone): complete response 4/13 vs 3/15; partial response 6/13 vs 9/15. Narrative only; no GRADE rating.
  1 study · 33 participants
  GRADE not reported