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Scientific Reports Jan 2024We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for... (Meta-Analysis)
Meta-Analysis
We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for Research on Cancer working groups. Following the PRISMA guidelines, a comprehensive literature search was conducted using the PubMed database. Pharmaceuticals with few studies on cancer risk were identified in systematic reviews; those with two or more studies were subjected to meta-analysis. For the meta-analysis, a random-effects model was used to calculate the summary relative risks (SRRs) and 95% confidence intervals (95% CIs). Heterogeneity across studies was presented using the Higgins I square value from Cochran's Q test. Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen + oncovin + procarbazine + prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen + ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide + bleomycin + cisplatin and treosulfan]. Cyclosporine and azathioprine reported increased skin cancer risk (SRR = 1.32, 95% CI 1.07-1.62; SRR = 1.56, 95% CI 1.25-1.93) compared to non-use. Cyclophosphamide increased bladder and hematologic cancer risk (SRR = 2.87, 95% CI 1.32-6.23; SRR = 2.43, 95% CI 1.65-3.58). Busulfan increased hematologic cancer risk (SRR = 6.71, 95% CI 2.49-18.08); melphalan was associated with hematologic cancer (SRR = 4.43, 95% CI 1.30-15.15). In the systematic review, methoxsalen + UV and MOPP were associated with an increased risk of skin and lung cancer, respectively. Our results can enhance persistent surveillance of group I pharmaceutical use, establish novel clinical strategies for patients with indications, and provide evidence for re-categorizing current group I pharmaceuticals into other groups.
Topics: Humans; Etoposide; Methoxsalen; Azathioprine; Melphalan; Busulfan; Neoplasms; Hematologic Neoplasms; Cyclophosphamide; Cyclosporins; Pharmaceutical Preparations
PubMed: 38172159
DOI: 10.1038/s41598-023-50602-6 -
Journal of Geriatric Oncology Nov 2020Several treatment options are available for the management of older adults with newly diagnosed patients with Multiple Myeloma (MM) who are ineligible for hematopoietic... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several treatment options are available for the management of older adults with newly diagnosed patients with Multiple Myeloma (MM) who are ineligible for hematopoietic cell transplantation (tiMM). We aimed to identify treatment options that provide the best balance in terms of efficacy and safety.
METHODS
We searched bibliographic databases and meeting libraries for search terms reflecting newly diagnosed and older and/or transplant-ineligible patients from inception to October 21, 2018. Phase II/III randomized trials comparing at least two first line treatment regimens for newly diagnosed tiMM were included. We extracted data on efficacy (progression free survival, PFS, overall survival and overall response rate) and safety (grade ¾ toxicities) and conducted network meta-analysis using Bayesian methods and random effects models. Relative ranking of treatment regimens was assessed using Surface under the cumulative ranking (SUCRA) probabilities.
RESULTS
We identified 27 trials involving 12,194 patients. For PFS, the four most effective regimens were: Daratumumab, Bortezomib, Melphalan and Prednisone (SUCRA 0.960) followed by Daratumumab, lenalidomide and dexamethasone (Dara_RD, SUCRA 0.847), Bortezomib, melphalan, prednisone, thalidomide maintenance with bortezomib-thalidomide (SUCRA 0.834) and Bortezomib, Lenalidomide and Dexamethasone (SUCRA 0.739). Among these four most efficacious regimens, toxicity profile was most favorable for Dara_RD (median additional AEs per patient vs dexamethasone = 0.74; 95% CrI 0.51-1.17; SUCRA 0.430).
CONCLUSION
Among first line tiMM regimens, increasing efficacy is associated with increased toxicity. We provide relative ranking of these regimens for both efficacy and safety. Future studies should incorporate geriatric assessments and frailty biomarkers to refine treatment decision-making for each individual patient.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Humans; Lenalidomide; Multiple Myeloma; Treatment Outcome
PubMed: 32513568
DOI: 10.1016/j.jgo.2020.05.013 -
Cancers Oct 2021Isolated limb perfusion (ILP) is a locoregional procedure indicated by the unresectable melanoma of the limbs. Its complexity and highly demanding multidisciplinary... (Review)
Review
BACKGROUND
Isolated limb perfusion (ILP) is a locoregional procedure indicated by the unresectable melanoma of the limbs. Its complexity and highly demanding multidisciplinary approach means that it is a technique only implemented in a few referral centers around the globe. This report aims to examine its potential role in the era of targeted therapies and immunotherapy by conducting a systematic review of the literature on ILP.
METHODS
PubMed, Embase and Cochrane Library were searched. The eligibility criteria included publications from 2000-2020 providing valid data o effectiveness, survival or toxicity. Studies in which the perfusion methodology was not clearly described, letters to the editor, non-systematic reviews and studies that applied outdated clinical guidelines were excluded. To rule out studies of a low methodological quality and assess the risk of bias, the following aspects were also required: a detailed description of the applied ILP regimen, the clinical context, follow-up periods, analyzed clinical endpoints, and the number of analyzed ILPs. The disagreements were resolved by consensus. The results are presented in tables and figures.
RESULTS
Twenty-seven studies including 2637 ILPs were selected. The median overall response rate was 85%, with a median complete response rate of 58.5%. The median overall survival was 38 months, with a 5-year overall survival of 35%. The toxicity was generally mild according to Wieberdink toxicity criteria.
DISCUSSION
ILP still offer a high efficacy in selected patients. The main limitation of our review is the heterogeneity and age of most of the articles, as well as the absence of clinical trials comparing ILP with other procedures, making it difficult to transfer its results to the current era.
CONCLUSIONS
ILP is still an effective and safe procedure for selected patients with unresectable melanoma of the limbs. In the era of targeted therapies and immunotherapy, ILP remains an acceptable and reasonable palliative treatment alternative, especially to avoid limb amputations. The ongoing clinical trials combining systemic therapies and ILP will provide more valuable information in the future to clarify the potential synergism of both strategies.
PubMed: 34771649
DOI: 10.3390/cancers13215485 -
The Cochrane Database of Systematic... Dec 2015This is the second update of the review first published in the Cochrane Database of Systematic Reviews in 2009, Issue 1. Epithelial ovarian cancer is diagnosed in over... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is the second update of the review first published in the Cochrane Database of Systematic Reviews in 2009, Issue 1. Epithelial ovarian cancer is diagnosed in over 200,000 women worldwide each year. Ten to 20% of women are diagnosed early, when there is still a good possibility of cure. The treatment of early-stage (stage I and IIa) disease involves surgery to remove the disease, often followed by chemotherapy (adjuvant chemotherapy). The largest clinical trials of adjuvant chemotherapy show an overall survival (OS) advantage with platinum-based chemotherapy; however the precise role and type of this treatment in subgroups of women with differing prognoses needs to be defined.
OBJECTIVES
To undertake a systematic review of the evidence for adjuvant chemotherapy in early-stage epithelial ovarian cancer to determine whether chemotherapy following surgery offers a survival advantage over the policy of observation following surgery (with chemotherapy reserved for treatment of disease recurrence); and to determine if clinical subgroups of women with differing prognoses, based on histological subtype or completeness of surgical staging, have more or less to gain from adjuvant chemotherapy.
SEARCH METHODS
We performed an electronic search using the Cochrane Gynaecological Cancer Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 3), MEDLINE (1948 to March week 5, 2015), and EMBASE (1980 to week 14, 2015). We developed the search strategy using free-text and medical subject headings (MeSH). We also searched registers of clinical trials and citation lists of included studies for potentially relevant studies.
SELECTION CRITERIA
We included randomised clinical trials (RCTs) of women with early stage (I/IIa) epithelial ovarian cancer staged at laparotomy.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed study quality of included RCTs. We resolved any disagreements by discussion with a third review author. We used random-effects methods for all meta-analyses, including subgroup analyses.
MAIN RESULTS
The original version of this Cochrane review included five RCTs involving 1277 women. In this 2015 update, no new studies met the inclusion criteria but we included an additional paper with mature data (10-year follow-up) relating to a previously included study (ICON1).We included four studies in the meta-analyses and considered them to be at a low risk of bias. Most study participants (> 95%) had stage I ovarian cancer. Meta-analysis of five-year data from three studies indicated that women who received adjuvant platinum-based chemotherapy had better overall survival (OS) than those who did not (Hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.53 to 0.93; 1008 women; 3 studies; I² statistic = 0%; high quality evidence). Likewise, meta-analysis of five-year data from four studies indicated that women who received adjuvant chemotherapy had better progression-free survival (PFS) than those who did not (HR 0.67, 95% CI 0.53 to 0.84; 1170 women, 4 studies; I² statistic = 0%; high quality evidence). These findings were robust over time, with 10-year HR estimates of 0.72 (95% CI 0.57 to 0.92; 925 women, 2 studies) and 0.67 (95% CI 0.53 to 0.83; 925 women, 2 studies) for OS and PFS, respectively (high quality evidence). The risk of death at 10 years follow-up favoured the adjuvant chemotherapy arm (0.76, 95% CI 0.62 to 0.94; 923 women, 2 studies; I² statistic = 0%), as did the findings for risk of progression at 10 years (RR 0.72, 95% CI 0.60 to 0.87; 925 women, 2 studies; I² statistic = 0%). Low quality evidence suggested that women with high-risk disease may have the most to gain from adjuvant chemotherapy. However, subgroup analyses could neither confirm nor exclude survival benefits in lower risk disease or in optimally staged disease. We found insufficient data to compare adverse events and long term risks between chemotherapy and observation groups.
AUTHORS' CONCLUSIONS
High-quality evidence indicates that adjuvant platinum-based chemotherapy is effective in prolonging survival in women with early stage (FIGO stage I/IIa) epithelial ovarian cancer. It remains uncertain whether women with low- and intermediate-risk early stage disease will benefit as much from adjuvant chemotherapy as women with high-risk disease. Decisions to use adjuvant chemotherapy (AC) in these women should be mindful of this uncertainty, and the uncertainty regarding adverse events. Treatment of women with lower risk disease should be individualised to take into account individual factors.
Topics: Antineoplastic Agents; Carboplatin; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Early Detection of Cancer; Female; Humans; Melphalan; Neoplasm Staging; Ovarian Neoplasms; Randomized Controlled Trials as Topic
PubMed: 26676202
DOI: 10.1002/14651858.CD004706.pub5 -
Clinical Hematology International 2024Globally, multiple myeloma (MM) ranks 24 among the most common cancers. The Middle East and Africa are affected by an increasing trend in MM incidence, owing to several...
BACKGROUND
Globally, multiple myeloma (MM) ranks 24 among the most common cancers. The Middle East and Africa are affected by an increasing trend in MM incidence, owing to several underlying factors. This systematic review aims to assess the epidemiology, patient characteristics, and treatment outcomes associated with MM in selected countries in the Middle East and Africa.
METHODS
An electronic search was performed in the PubMed/MEDLINE database. Abstracts presented at the annual meetings of the American Society of Clinical Oncology, American Society of Hematology, and European Society for Medical Oncology and the GLOBOCAN registry were searched. Qualitative analysis was performed.
RESULTS
A total of 412 articles were screened, and 14 were selected. The five-year prevalence per 100,000 gathered from country-wise GLOBOCAN data ranged between 155 in Kuwait and 5,625 in North Africa. The identified treatment options were proteasome inhibitors such as bortezomib, drugs such as thalidomide, lenalidomide, dexamethasone, melphalan, and cyclophosphamide, and newer drugs such as daratumumab.
CONCLUSION
Improved diagnostic capability has increased the incidence of MM in this region. However, advanced drugs and treatment regimens remain unaffordable in many countries of these regions. Therefore, understanding the trends of the disease and improving healthcare settings are imperative.
PubMed: 38817690
DOI: 10.46989/001c.92555 -
The Cochrane Database of Systematic... Sep 2021Ewing sarcomas are solid tumours of the bone and soft tissue, that usually affect children, adolescents, and young adults. The incidence is about three cases per million... (Review)
Review
BACKGROUND
Ewing sarcomas are solid tumours of the bone and soft tissue, that usually affect children, adolescents, and young adults. The incidence is about three cases per million a year, with a peak incidence at 12 years of age. Metastatic disease is detected in about 20 % to 30% of people, and is typically found in the lungs, bone, bone marrow, or a combination of these. Presence of metastatic disease at diagnosis (primary metastatic disease) is the most important adverse prognostic factor, and is associated with a five-year survival lower than 30%. High-dose chemotherapy (HDC) followed by autologous haematopoietic cell transplantation (AHCT) is used in various solid tumours with unfavourable prognoses in children, adolescents, and young adults. It has also been used as rescue after multifocal radiation of metastases. The hypothesis is that HDC regimens may overcome the resistance to standard multidrug chemotherapy and improve survival rates.
OBJECTIVES
To assess the effects of high-dose chemotherapy with autologous haematopoietic cell transplantation compared with conventional chemotherapy in improving event-free survival, overall survival, quality-adjusted survival, and progression-free survival in children, adolescents, and young adults with primary metastatic Ewing sarcoma, and to determine the toxicity of the treatment.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, conference proceedings from major international cancer-related conferences, and ongoing trial registers until January 2020. We also searched reference lists of included articles and review articles.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) or (historical) controlled clinical trials (CCTs) comparing the effectiveness of HDC and AHCT with conventional chemotherapy for children, adolescents, and young adults (younger than 30 years at the date of diagnostic biopsy) with primary metastatic Ewing sarcoma.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We identified one RCT, which investigated the effects of HDC with AHCT versus conventional chemotherapy with whole lung irradiation (WLI) in people with Ewing sarcoma metastasised to the lungs only at diagnosis. Only a selection of the participants were eligible for our review (N = 267: HDC with AHCT group N = 134; control group N = 133). There may be no difference in event-free survival between the two treatment groups (hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.59 to 1.17; low-certainty evidence). We downgraded one level each because of study limitations and imprecision. Overall survival and toxicity were not reported separately for the participants eligible for this review, while quality-adjusted survival and progression-free survival were not reported at all. We did not identify any studies that addressed children, adolescents, and young adults with Ewing sarcoma with metastases to other locations.
AUTHORS' CONCLUSIONS
In people with Ewing sarcoma with primary metastases to locations other than the lungs, there is currently no evidence from RCTs or CCTs to determine the efficacy of HDC with AHCT compared to conventional chemotherapy. Based on low-certainty evidence from one study (267 participants), there may be no difference in event-free survival between children, adolescents, and young adults with primary pulmonary metastatic Ewing sarcoma who receive HDC with AHCT and those who receive conventional chemotherapy with WLI. Further high-quality research is needed. Results are anticipated for the EuroEwing 2008R3 study, in which the effects of HDC with treosulfan and melphalan followed by AHCT on survival, in people with Ewing sarcoma with metastatic disease to bone, other sites, or both were explored. Achieving high-quality studies in a selection of people with rare sarcoma requires long-term, multi-centre, international participant inclusion.
Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Hematopoietic Stem Cell Transplantation; Humans; Progression-Free Survival; Sarcoma, Ewing; Transplantation, Autologous; Young Adult
PubMed: 34472082
DOI: 10.1002/14651858.CD011405.pub2 -
Oncotarget Jul 2016We performed a network meta-analysis of randomized controlled trials (RCTs) to compare the efficacy of several intravesical chemotherapeutic (IVC) agents after... (Meta-Analysis)
Meta-Analysis Review
Single, immediate postoperative instillation of chemotherapy in non-muscle invasive bladder cancer: a systematic review and network meta-analysis of randomized clinical trials using different drugs.
We performed a network meta-analysis of randomized controlled trials (RCTs) to compare the efficacy of several intravesical chemotherapeutic (IVC) agents after transurethral resection of bladder tumor (TURB) in non-muscle invasive bladder cancer patients. The literature search was conducted using the Embase, Scopus and PubMed databases for RCTs, including patients with single or multiple, primary or recurrent stage Ta or T1 urothelial carcinoma of the bladder managed with a single, immediate instillation of IVC after TURB. Thirteen RCTs met the eligibility criteria. Pair-wise meta-analysis (direct comparison) showed that pirarubicin [hazard ratio (HR): 0.31], epirubicin (HR: 0.62), and MMC (HR: 0.40) were the most effective drugs for reducing tumor recurrence. Bayesian network meta-analysis (indirect comparison) revealed that treatment with pirarubicin (HR: 0.31), MMC (HR: 0.44), or epirubicin (HR: 0.60) was associated with prolonged recurrence-free survival. Among the drugs examined, only pirarubicin reduced disease progression compared to controls. These results suggest that a single, immediate administration of IVC with pirarubicin, MMC, or epirubicin is associated with prolonged recurrence-free survival following TURB in non-muscle invasive bladder cancer patients, though only pirarubicin also reduced disease progression.
Topics: Administration, Intravesical; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Cyclophosphamide; Doxorubicin; Epirubicin; Humans; Melphalan; Network Meta-Analysis; Semustine; Treatment Outcome; Urinary Bladder Neoplasms
PubMed: 27323781
DOI: 10.18632/oncotarget.9991 -
Indian Journal of Hematology & Blood... Apr 2018Bortezomib began to be used in the treatment of light chain (AL) amyloidosis in recent years. We performed the first meta-analysis of randomized clinical trials and...
Bortezomib began to be used in the treatment of light chain (AL) amyloidosis in recent years. We performed the first meta-analysis of randomized clinical trials and clinical controlled trials to evaluate the effect and safety of bortezomib treatment for AL amyloidosis. We conducted a search (until July 2016) in electronic databases (PubMed databases and the Cochrane Central Register of Controlled Trials bases from the year 2003). There were 205 records we searched and eight studies was included (n = 617 persons). We demonstrated that bortezomib treatment significantly improved overall response rate (ORR), complete response, a cardiac response rate, 2-year overall survival and the risk of neuropathy and reduced overall mortality compared to controls without bortezomib therapy. From the comparison and subgroup analysis of ORR between bortezomib group and no bortezomib group, the patients with bortezomib had a higher ORR, especially patients pretreated with bortezomib before high-dose melphalan followed by autologous stem cell transplant compared to no pretreatment. In addition, patients with bortezomib in standard dosage had significantly higher ORR. According to our results, bortezomib should be used in AL amyloidosis patients to improve response rate and survival rate and future relevant randomized controlled trials require to be performed.
PubMed: 29622862
DOI: 10.1007/s12288-018-0937-x -
Biology of Blood and Marrow... Apr 2019Fludarabine with busulfan (FB) or melphalan (FM) are 2 more commonly used reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (HCT).We... (Meta-Analysis)
Meta-Analysis
Choosing a Reduced-Intensity Conditioning Regimen for Allogeneic Stem Cell Transplantation, Fludarabine/Busulfan versus Fludarabine Melphalan: A Systematic Review and Meta-Analysis.
Fludarabine with busulfan (FB) or melphalan (FM) are 2 more commonly used reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (HCT).We present a systematic review and meta-analysis of studies comparing these 2 RIC regimens. We searched electronic databases from inception through November 1, 2017 for literature searches to identify relevant studies. A DerSimonian random effects model was used to measure efficacy outcomes; hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) are reported. Seven studies, including a total of 1955 patients, met criteria for inclusion, of which 6 were included in the overall pooled analysis because of repetition of some patients in 2 studies. Three studies were included in the subgroup analysis of acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS) and 2 in the subgroup analysis of lymphoid malignancies. Overall survival (OS) and progression-free survival were not statistically significantly different between the 2 RIC regimens in analysis of all studies. However, OS was better with FM in subgroup analysis of AML/MDS studies (HR, .83; 95% CI, .73 to .95). Nonrelapse mortality was lower with FB (HR, .64; 95% CI, .46 to .89), whereas relapse was lower with FM (HR, 1.52; 95% CI, 1.13 to 2.06) in the analysis of all studies. This meta-analysis shows that FB and FM are associated with a similar OS in patients undergoing HCT. Relapse rates are lower with FM but at the cost of higher nonrelapse mortality.
Topics: Busulfan; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Melphalan; Transplantation Conditioning; Transplantation, Homologous; Vidarabine
PubMed: 30471339
DOI: 10.1016/j.bbmt.2018.11.016 -
The Cochrane Database of Systematic... Dec 2015Oral mucositis is a side effect of chemotherapy, head and neck radiotherapy, and targeted therapy, affecting over 75% of high risk patients. Ulceration can lead to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Oral mucositis is a side effect of chemotherapy, head and neck radiotherapy, and targeted therapy, affecting over 75% of high risk patients. Ulceration can lead to severe pain and difficulty eating and drinking, which may necessitate opioid analgesics, hospitalisation and nasogastric or intravenous nutrition. These complications may lead to interruptions or alterations to cancer therapy, which may reduce survival. There is also a risk of death from sepsis if pathogens enter the ulcers of immunocompromised patients. Ulcerative oral mucositis can be costly to healthcare systems, yet there are few preventive interventions proven to be beneficial. Oral cryotherapy is a low-cost, simple intervention which is unlikely to cause side-effects. It has shown promise in clinical trials and warrants an up-to-date Cochrane review to assess and summarise the international evidence.
OBJECTIVES
To assess the effects of oral cryotherapy for preventing oral mucositis in patients with cancer who are receiving treatment.
SEARCH METHODS
We searched the following databases: the Cochrane Oral Health Group Trials Register (to 17 June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 5), MEDLINE via Ovid (1946 to 17 June 2015), EMBASE via Ovid (1980 to 17 June 2015), CANCERLIT via PubMed (1950 to 17 June 2015) and CINAHL via EBSCO (1937 to 17 June 2015). We searched the US National Institutes of Health Trials Registry, and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching databases.
SELECTION CRITERIA
We included parallel-design randomised controlled trials (RCTs) assessing the effects of oral cryotherapy in patients with cancer receiving treatment. We used outcomes from a published core outcome set registered on the COMET website.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the results of electronic searches, extracted data and assessed risk of bias. We contacted study authors for information where feasible. For dichotomous outcomes, we reported risk ratios (RR) and 95% confidence intervals (CI). For continuous outcomes, we reported mean differences (MD) and 95% CIs. We pooled similar studies in random-effects meta-analyses. We reported adverse effects in a narrative format.
MAIN RESULTS
We included 14 RCTs analysing 1280 participants. The vast majority of participants did not receive radiotherapy to the head and neck, so this review primarily assesses prevention of chemotherapy-induced oral mucositis. All studies were at high risk of bias. The following results are for the main comparison: oral cryotherapy versus control (standard care or no treatment). Adults receiving fluorouracil-based (5FU) chemotherapy for solid cancersOral cryotherapy probably reduces oral mucositis of any severity (RR 0.61, 95% CI 0.52 to 0.72, 5 studies, 444 analysed, moderate quality evidence). In a population where 728 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 444 (95% CI 379 to 524). The number needed to treat to benefit one additional person (NNTB), i.e. to prevent them from developing oral mucositis, is 4 people (95% CI 3 to 5).The results were similar for moderate to severe oral mucositis (RR 0.52, 95% CI 0.41 to 0.65, 5 studies, 444 analysed, moderate quality evidence). NNTB 4 (95% CI 4 to 6).Severe oral mucositis is probably reduced (RR 0.40, 95% CI 0.27 to 0.61, 5 studies, 444 analysed, moderate quality evidence). Where 300 per 1000 would develop severe oral mucositis, oral cryotherapy would reduce this to 120 (95% CI 81 to 183), NNTB 6 (95% CI 5 to 9). Adults receiving high-dose melphalan-based chemotherapy before haematopoietic stem cell transplantation (HSCT)Oral cryotherapy may reduce oral mucositis of any severity (RR 0.59, 95% CI 0.35 to 1.01, 5 studies, 270 analysed, low quality evidence). Where 824 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 486 (95% CI reduced to 289 to increased to 833). The NNTB is 3, although the uncertainty surrounding the effect estimate means that the 95% CI ranges from 2 NNTB, to 111 NNTH (number needed to treat in order to harm one additional person, i.e. for one additional person to develop oral mucositis).The results were similar for moderate to severe oral mucositis (RR 0.43, 95% CI 0.17 to 1.09, 5 studies, 270 analysed, low quality evidence). NNTB 3 (95% CI 2 NNTB to 17 NNTH).Severe oral mucositis is probably reduced (RR 0.38, 95% CI 0.20 to 0.72, 5 studies, 270 analysed, moderate quality evidence). Where 427 per 1000 would develop severe oral mucositis, oral cryotherapy would reduce this to 162 (95% CI 85 to 308), NNTB 4 (95% CI 3 to 9).Oral cryotherapy was shown to be safe, with very low rates of minor adverse effects, such as headaches, chills, numbness/taste disturbance, and tooth pain. This appears to contribute to the high rates of compliance seen in the included studies.There was limited or no evidence on the secondary outcomes of this review, or on patients undergoing other chemotherapies, radiotherapy, targeted therapy, or on comparisons of oral cryotherapy with other interventions or different oral cryotherapy regimens. Therefore no further robust conclusions can be made. There was also no evidence on the effects of oral cryotherapy in children undergoing cancer treatment.
AUTHORS' CONCLUSIONS
We are confident that oral cryotherapy leads to large reductions in oral mucositis of all severities in adults receiving 5FU for solid cancers. We are less confident in the ability of oral cryotherapy to reduce oral mucositis in adults receiving high-dose melphalan before HSCT. Evidence suggests that it does reduce oral mucositis in these adults, but we are less certain about the size of the reduction, which could be large or small. However, we are confident that there is an appreciable reduction in severe oral mucositis in these adults.This Cochrane review includes some very recent and currently unpublished data, and strengthens international guideline statements for adults receiving the above cancer treatments.
Topics: Adult; Antineoplastic Agents; Cryotherapy; Fluorouracil; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Mouth Diseases; Myeloablative Agonists; Neoplasms; Pain; Randomized Controlled Trials as Topic; Stomatitis
PubMed: 26695736
DOI: 10.1002/14651858.CD011552.pub2