Cochrane · intervention · CD011990
Interventions for preventing oral mucositis in patients with cancer receiving treatment: cytokines and growth factors
Riley, P, Glenny, AM, Worthington, HV, et al. · Cochrane Database of Systematic Reviews · 2017 · Cochrane Library
Full textEvery question was extracted from the full review (methods and results), not only its Summary of Findings table.
Questions
69
current version
GRADE rated
13
No studies
2
Included studies
35
as reported
No studies 2 · 2.9%Ungraded 54 · 78.3%Very low 5 · 7.2%Low 5 · 7.2%Moderate 2 · 2.9%High 1 · 1.4%
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 | All patients with cancer who are receiving treatment | 35 studies, 3102 participants analysed (3218 randomised); patients being treated for cancer, aged 1 to 87 years; almost all adults (only occasional children) |
| Intervention | Growth factors and cytokines for the prevention of oral mucositis (keratinocyte growth factor; colony-stimulating factors; epidermal growth factor; transforming growth factor-beta; whey-derived growth factor; interleukin-11; ATL-104; trefoil factor); also targeted therapy-induced stomatitis had such studies been identified | Keratinocyte growth factor (KGF) (n=16); Granulocyte-macrophage colony-stimulating factor (GM-CSF) (n=8); Granulocyte-colony stimulating factor (G-CSF) (n=6); Epidermal growth factor (EGF) (n=2); Intestinal trefoil factor (ITF) (n=1); Erythropoietin (n=1); Transforming growth factor (TGF-beta2) (n=1) |
| Comparison | Usual care; no treatment; any other treatment to prevent oral mucositis; different growth factors/cytokines or different regimens (head-to-head) | Placebo (n=28); No treatment (n=4); Chlorhexidine (n=1); Sucralfate (n=2) |
| Outcomes | Mucositis of any severity (dichotomised: any 0 vs 1+; moderate to severe 0-1 vs 2+; severe 0-2 vs 3+); Interruptions to cancer treatment; Oral pain; Quality of life; Normalcy of diet (incl. PEG feeding tubes or total parenteral nutrition); Adverse events; Number of days in hospital; Number of days of treatment with opioid analgesics; Number of days unable to take medicine orally | Oral mucositis incidence (n=35); Interruptions to cancer treatment (n=8); Oral pain (n=15); Quality of life (n=0); Normalcy of diet (n=17); Adverse events (n=35); Number of days in hospital (n=9); Number of days of treatment with opioid analgesics (n=11); Number of days unable to take medicine orally (n=0) |
| Study designs | All randomised controlled trials (RCTs) of parallel design; cross-over studies included using first-period data only, treated as parallel studies | Randomised controlled trials of parallel design (35 RCTs) |
| Timing | Not specified | Not reported |
Search date: 2017-05. Databases: Cochrane Oral Health's Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE Ovid; Embase Ovid; CINAHL EBSCO; CANCERLIT PubMed; ClinicalTrials.gov; WHO International Clinical Trials Registry Platform
Questions and results
Show all 2 versionsKeratinocyte growth factor (KGF; palifermin or repifermin), intravenous vs Placebo
Population: Adults with cancer receiving treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Oral mucositis (any severity) BMT/SCT after conditioning for haematological cancers | RR 0.96 [0.88, 1.05] | 4 studies · 655 participants | Ungraded |
Interruptions to cancer treatment (chemotherapy delays/discontinuations) RT to head and neck with cisplatin/fluorouracil | RR 0.96 [0.62, 1.47] | 2 studies · 374 participants | Ungraded |
Normalcy of diet (mean worst ability to eat, 1 to 4 scale) BMT/SCT after conditioning for haematological cancers | MD -0.50 [-1.21, 0.21] | 1 study · 42 participants | Ungraded |
Oral pain (mean pain score, 0 to 4 scale) RT to head and neck with cisplatin/fluorouracil | MD -0.12 [-0.27, 0.02] | 2 studies · 374 participants | Ungraded |
Oral mucositis (severe) Chemotherapy alone for mixed cancers | RR 0.30 [0.14, 0.65] 154 per 1000 vs 46 per 1000 | 3 studies · 263 participants | Low Downgraded: imprecision, publication bias |
Oral mucositis (any severity) Children | Two studies of KGF versus placebo in children were unclear in reporting; no usable data could be presented | 2 studies | Ungraded |
Adverse events | Adverse events attributed to KGF were typically oral-related or skin-related; mostly mild to moderate with very few serious events; reporting poor and inconsistent, not appropriate to meta-analyse (SoF comments cell,… | 16 studies | Ungraded |
Interruptions to cancer treatment (unscheduled radiotherapy breaks of 5 or more days) RT to head and neck with cisplatin/fluorouracil | RR 1.01 [0.65, 1.59] | 3 studies · 473 participants | Ungraded |
Number of days in hospital BMT/SCT after conditioning for haematological cancers | MD 0.00 [-1.64, 1.64] | 1 study · 281 participants | Ungraded |
Quality of life | No studies reported this outcome (planned secondary outcome not measured by any study in the review) | 0 studies | No studies |
Oral mucositis (moderate to severe) BMT/SCT after conditioning for haematological cancers | RR 0.89 [0.80, 0.99] 848 per 1000 vs 755 per 1000 | 6 studies · 852 participants | Low Downgraded: inconsistency, publication bias |
Number of days unable to take medicine orally | No studies reported this outcome (planned secondary outcome not measured by any study in the review) | 0 studies | No studies |
Oral pain (mean worst pain, 0 to 10 scale) BMT/SCT after conditioning for haematological cancers | MD -0.85 [-3.00, 1.30] | 1 study · 42 participants | Ungraded |
Normalcy of diet (supplemental nutrition: TPN, PEG, nasogastric tube or IV hydration) RT to head and neck with cisplatin/fluorouracil | RR 1.03 [0.77, 1.37] | 3 studies · 473 participants | Ungraded |
Oral mucositis (moderate to severe) RT to head and neck with cisplatin/fluorouracil | RR 0.91 [0.83, 1.00] 932 per 1000 vs 848 per 1000 | 3 studies · 471 participants | Moderate Downgraded: inconsistency |
Oral mucositis (severe) BMT/SCT after conditioning for haematological cancers | RR 0.85 [0.65, 1.11] 677 per 1000 vs 575 per 1000 | 6 studies · 852 participants | Low Downgraded: inconsistency, publication bias |
Oral mucositis (moderate to severe) Chemotherapy alone for mixed cancers | RR 0.56 [0.45, 0.70] 631 per 1000 vs 353 per 1000 | 4 studies · 344 participants | Moderate Downgraded: publication bias |
Oral mucositis (any severity) RT to head and neck with cisplatin/fluorouracil | RR 0.95 [0.90, 1.00] | 2 studies · 374 participants | Ungraded |
Normalcy of diet (total parenteral nutrition) BMT/SCT after conditioning for haematological cancers | RR 0.89 [0.58, 1.34] | 4 studies · 714 participants | Ungraded |
Number of days of treatment with opioid analgesics BMT/SCT after conditioning for haematological cancers | MD -1.41 [-3.33, 0.51] | 2 studies · 323 participants | Ungraded |
Oral mucositis (any severity) Chemotherapy alone for mixed cancers | RR 0.71 [0.60, 0.85] | 2 studies · 215 participants | Ungraded |
Oral mucositis (severe) RT to head and neck with cisplatin/fluorouracil | RR 0.79 [0.69, 0.90] 700 per 1000 vs 553 per 1000 | 3 studies · 471 participants | High |
Granulocyte-macrophage colony-stimulating factor (GM-CSF) vs Placebo or no treatment
Population: Adults with cancer receiving treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Adverse events | Adverse events attributed to GM-CSF typically bone pain, nausea, fever and headache; not reported as serious; reporting poor and inconsistent (SoF comments cell, not GRADE-rated) | 8 studies | Ungraded |
Oral mucositis (any severity) BMT/SCT after conditioning for haematological cancers | RR 0.91 [0.80, 1.04] | 1 study · 90 participants | Ungraded |
Oral mucositis (moderate to severe) RT to head and neck | RR 0.72 [0.49, 1.06] 929 per 1000 vs 669 per 1000 | 1 study · 29 participants | Very low Downgraded: risk of bias, imprecision, indirectness, publication bias |
Oral pain (mean pain score, 0 to 10 scale) BMT/SCT after conditioning for haematological cancers | MD 0.60 [-0.85, 2.05] | 1 study · 90 participants | Ungraded |
Oral mucositis (any severity) RT to head and neck | RR 1.01 [0.82, 1.23] | 1 study · 29 participants | Ungraded |
Oral mucositis (severe) BMT/SCT after conditioning for mixed cancers | RR 0.74 [0.33, 1.67] 347 per 1000 vs 257 per 1000 | 3 studies · 235 participants | Low Downgraded: imprecision, inconsistency |
Oral mucositis (severe) Chemotherapy alone for mixed cancers | RR 0.59 [0.05, 7.11] 500 per 1000 vs 295 per 1000 | 2 studies · 65 participants | Very low Downgraded: risk of bias, imprecision, inconsistency |
Normalcy of diet (total parenteral nutrition) BMT/SCT after conditioning for haematological cancers | RR 1.10 [0.63, 1.91] | 1 study · 36 participants | Ungraded |
Oral mucositis (moderate to severe) BMT/SCT after conditioning for haematological cancers | RR 0.94 [0.79, 1.13] 839 per 1000 vs 789 per 1000 | 1 study · 109 participants | Very low Downgraded: imprecision, indirectness |
Number of days of treatment with opioid analgesics BMT/SCT after conditioning for haematological cancers | MD -1.10 [-1.91, -0.29] | 1 study · 90 participants | Ungraded |
Normalcy of diet (tube feeding) RT to head and neck | RR 0.31 [0.01, 7.09] | 1 study · 29 participants | Ungraded |
Oral mucositis (severe) RT to head and neck | RR 0.31 [0.01, 7.09] 71 per 1000 vs 22 per 1000 | 1 study · 29 participants | Very low Downgraded: risk of bias, imprecision, indirectness, publication bias |
Granulocyte-colony stimulating factor (G-CSF) vs Placebo or no treatment
Population: Adults with cancer receiving treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Oral mucositis (any severity) Chemotherapy alone for lung cancer | RR 0.59 [0.40, 0.87] | 1 study · 195 participants | Ungraded |
Adverse events | Limited evidence of adverse events for G-CSF; 2 of 6 studies did not report; low rates of mild to moderate events, most commonly bone pain (SoF comments cell, not GRADE-rated) | 6 studies | Ungraded |
Oral mucositis (any severity) RT to head and neck | RR 1.02 [0.86, 1.22] | 2 studies · 54 participants | Ungraded |
Oral mucositis (severe) RT to head and neck | RR 0.37 [0.15, 0.87] 519 per 1000 vs 192 per 1000 | 2 studies · 54 participants | Low Downgraded: imprecision |
Interruptions to cancer treatment (radiotherapy interruptions) RT to head and neck | RR 0.22 [0.01, 4.31] | 1 study · 40 participants | Ungraded |
Oral mucositis (moderate to severe) Chemotherapy alone for breast cancer | RR 0.33 [0.12, 0.95] 1000 per 1000 vs 330 per 1000 | 1 study · 14 participants | Very low Downgraded: risk of bias, imprecision, indirectness |
Normalcy of diet (percutaneous endoscopic gastrostomy) RT to head and neck | RR 0.16 [0.01, 2.86] | 1 study · 40 participants | Ungraded |
Epidermal growth factor (EGF), oral spray vs Placebo
Population: Adults with cancer receiving treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Oral mucositis (moderate to severe) Chemoradiotherapy to the head and neck | RR 1.06 [0.78, 1.43] | 1 study · 136 participants | Ungraded |
Adverse events | Adverse events narratively reported; no serious events attributed to EGF (not GRADE-rated) | 2 studies | Ungraded |
Oral mucositis (severe) Chemoradiotherapy to the head and neck | RR 1.03 [0.59, 1.80] | 1 study · 136 participants | Ungraded |
Interruptions to cancer treatment (radiotherapy breaks longer than two days) Radiotherapy to the head and neck | RR 4.38 [0.25, 75.44] | 1 study · 113 participants | Ungraded |
Oral mucositis (moderate to severe) Radiotherapy to the head and neck | RR 0.67 [0.45, 0.99] | 1 study · 103 participants | Ungraded |
Normalcy of diet (total parenteral nutrition) Chemoradiotherapy to the head and neck | RR 1.03 [0.55, 1.94] | 1 study · 136 participants | Ungraded |
Intestinal trefoil factor (ITF), oral spray vs Placebo
Population: Adults receiving chemotherapy alone for colorectal cancer
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Oral mucositis (any severity) | RR 0.52 [0.35, 0.79] | 1 study · 99 participants | Ungraded |
Oral mucositis (moderate to severe) | RR 0.22 [0.10, 0.48] | 1 study · 99 participants | Ungraded |
Adverse events | Adverse events narratively reported (not GRADE-rated) | 1 study | Ungraded |
Oral mucositis (severe) | RR 1.52 [0.06, 36.39] | 1 study · 99 participants | Ungraded |
Erythropoietin mouthwash vs Placebo
Population: Adults receiving bone marrow/stem cell transplantation after conditioning therapy for haematological cancers
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Oral mucositis (moderate to severe) | RR 0.43 [0.24, 0.79] | 1 study · 80 participants | Ungraded |
Oral mucositis (severe) | RR 0.40 [0.14, 1.17] | 1 study · 80 participants | Ungraded |
Oral mucositis (any severity) | RR 0.35 [0.21, 0.60] | 1 study · 80 participants | Ungraded |
Number of days in hospital | MD -2.95 [-7.73, 1.83] | 1 study · 80 participants | Ungraded |
Transforming growth factor-beta(2) (TGF-beta2) vs Placebo
Population: Adults receiving chemotherapy alone for colorectal cancer
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Oral mucositis (any severity) | RR 0.10 [0.01, 1.71] | 1 study · 13 participants | Ungraded |
Keratinocyte growth factor (KGF), higher dose/regimen vs Keratinocyte growth factor (KGF), different (lower) dose/regimen
Population: Adults with cancer receiving treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Oral mucositis (any severity) | Some inconsistent evidence from which no conclusions can be drawn regarding different dosages of KGF (Analyses 2.1 to 2.8); no pooled estimate reported | NR | Ungraded |
Keratinocyte growth factor (KGF), intravenous vs Chlorhexidine mouthwash
Population: Children with acute lymphoblastic leukaemia receiving chemotherapy alone
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Oral mucositis (any severity) Children | RR 0.67 [0.54, 0.85] | 1 study · 90 participants | Ungraded |
Oral mucositis (moderate to severe) Children | RR 0.12 [0.05, 0.28] | 1 study · 90 participants | Ungraded |
Oral mucositis (severe) Children | RR 0.01 [0.00, 0.19] | 1 study · 90 participants | Ungraded |
Granulocyte-macrophage colony-stimulating factor (GM-CSF), higher dose (1260 to 12,600 micrograms) vs Granulocyte-macrophage colony-stimulating factor (GM-CSF), lower dose (12.6 to 126 micrograms)
Population: Adults receiving chemotherapy alone for breast cancer
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Oral mucositis (severe) | RR 2.75 [1.07, 7.04] | 1 study · 36 participants | Ungraded |
Granulocyte-macrophage colony-stimulating factor (GM-CSF), mouthwash vs Sucralfate mouthwash
Population: Adults receiving radiotherapy to the head and neck
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Normalcy of diet (percutaneous endoscopic gastrostomy) RT to head and neck | RR 0.18 [0.01, 3.56] | 1 study · 40 participants | Ungraded |
Interruptions to cancer treatment RT to head and neck | RR 0.13 [0.01, 2.36] | 1 study · 40 participants | Ungraded |
Oral mucositis (moderate to severe) RT to head and neck | RR 0.96 [0.80, 1.14] | 1 study · 40 participants | Ungraded |
Oral mucositis (severe) RT to head and neck | RR 0.54 [0.24, 1.21] | 1 study · 40 participants | Ungraded |
Granulocyte-colony stimulating factor (G-CSF; pegfilgrastim, single dose) vs Granulocyte-colony stimulating factor (G-CSF; filgrastim, multiple doses)
Population: Children receiving bone marrow/stem cell transplantation after conditioning therapy for mixed cancers
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Oral mucositis (moderate to severe) Children | RR 0.78 [0.55, 1.11] | 1 study · 61 participants | Ungraded |
Normalcy of diet (total parenteral nutrition) Children | RR 1.00 [0.94, 1.06] | 1 study · 61 participants | Ungraded |
Oral mucositis (any severity) Children | RR 1.02 [0.82, 1.27] | 1 study · 61 participants | Ungraded |
Intestinal trefoil factor (ITF), lower dose (336 mg) vs Intestinal trefoil factor (ITF), higher dose (2688 mg)
Population: Adults receiving chemotherapy alone for colorectal cancer
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Oral mucositis (any severity) | Insufficient evidence to determine whether lower (336 mg) or higher (2688 mg) dose performs better (Analyses 11.1 to 11.3); no pooled estimate reported | 1 study · 66 participants | Ungraded |