-
PloS One 2014Amifostine is the most clinical used chemical radioprotector, but its effect in patients treated with radiation is not consistent. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Amifostine is the most clinical used chemical radioprotector, but its effect in patients treated with radiation is not consistent.
METHODS
By searching Medline, CENTRAL, EMBASE, ASCO, ESMO, and CNKI databases, the published randomized controlled trials (RCTs) about the efficacy of amifostine in HNSCC patients treated with radiotherapy were collected. The pooled efficacy and side effects of this drug were calculated by RevMan software.
RESULTS
Seventeen trials including a total of 1167 patients (604 and 563 each arm) were analyzed in the meta-analysis. The pooled data showed that the use of amifostine significantly reduce the risk of developing Grade 3-4 mucositis (relative risk [RR],0.72; 95% confidence interval [CI],0.54-0.95; p<0.00001), Grade 2-4 acute xerostomia (RR,0.70; 95%CI,0.52-0.96; p = 0.02), or late xerostomia (RR,0.60; 95%CI,0.49-0.74; p<0.00001) and Grade 3-4 dysphagia (RR,0.39; 95%CI,0.17-0.92; p = 0.03). However, subgroup analysis demonstrated that no statistically significant reduction of Grade 3-4 mucositis (RR,0.97; 95% CI,0.74-1.26; p = 0.80), Grade 2-4 acute xerostomia (RR,0.35; 95%CI,0.02-5.44; p = 0.45), or late xerostomia (RR,0.40; 95%CI,0.13-1.24; p = 0.11) and Grade 3-4 dysphagia (RR,0.23; 95%CI,0.01-4.78; p = 0.35) was observed in patients treated with concomitant chemoradiotherapy. Compared with placebo or observation, amifostine does not show tumor protective effect in complete response (RR,1.02; 95%CI,0.89-1.17; p = 0.76) and partial response (RR,0.90; 95%CI, 0.56-1.44; p = 0.66). For the hematologic side effect, no statistical difference of Grade 3-4 leucopenia (RR,0.60; 95%CI,0.35-1.05; p = 0.07), anemia (RR,0.80; 95%CI, 0.42-1.53; p = 0.50) and thrombocytopenia (RR,0.43; 95%CI,0.16-1.15; p = 0.09) were found between amifostine and control groups. The most common amifostine related side effects were nausea, emesis, hypotension and allergic with an average incidence rate (Grade 3-4) of 5%, 6%, 4% and 4% respectively.
CONCLUSION
This systematic review showed that amifostine significantly reduce the serious mucositis, acute/late xerastomia and dysphagia without protection of the tumor in HNSCC patients treated with radiotherapy. And the toxicities of amifostine were generally acceptable.
Topics: Amifostine; Carcinoma, Squamous Cell; Combined Modality Therapy; Head and Neck Neoplasms; Humans; Radiation Injuries; Randomized Controlled Trials as Topic; Squamous Cell Carcinoma of Head and Neck
PubMed: 24788761
DOI: 10.1371/journal.pone.0095968 -
The Cochrane Database of Systematic... Mar 2014Cisplatin and several related antineoplastic drugs used to treat many types of solid tumours are neurotoxic, and most patients completing a full course of cisplatin... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cisplatin and several related antineoplastic drugs used to treat many types of solid tumours are neurotoxic, and most patients completing a full course of cisplatin chemotherapy develop a clinically detectable sensory neuropathy. Effective neuroprotective therapies have been sought.
OBJECTIVES
To examine the efficacy and safety of purported chemoprotective agents to prevent or limit the neurotoxicity of cisplatin and related drugs.
SEARCH METHODS
On 4 March 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and CINAHL Plus for randomised trials designed to evaluate neuroprotective agents used to prevent or limit neurotoxicity of cisplatin and related drugs among human patients.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) or quasi-RCTs in which the participants received chemotherapy with cisplatin or related compounds, with a potential chemoprotectant (acetylcysteine, amifostine, adrenocorticotrophic hormone (ACTH), BNP7787, calcium and magnesium (Ca/Mg), diethyldithiocarbamate (DDTC), glutathione, Org 2766, oxcarbazepine, or vitamin E) compared to placebo, no treatment, or other treatments. We considered trials in which participants underwent evaluation zero to six months after completing chemotherapy using quantitative sensory testing (the primary outcome) or other measures including nerve conduction studies or neurological impairment rating using validated scales (secondary outcomes).
DATA COLLECTION AND ANALYSIS
Two review authors assessed each study, extracted the data and reached consensus, according to standard Cochrane methodology.
MAIN RESULTS
As of 2013, the review includes 29 studies describing nine possible chemoprotective agents, as well as description of two published meta-analyses. Among these trials, there were sufficient data in some instances to combine the results from different studies, most often using data from secondary non-quantitative measures. Nine of the studies were newly included at this update. Few of the included studies were at a high risk of bias overall, although often there was too little information to make an assessment. At least two review authors performed a formal review of an additional 44 articles but we did not include them in the final review for a variety of reasons.Of seven eligible amifostine trials (743 participants in total), one used quantitative sensory testing (vibration perception threshold) and demonstrated a favourable outcome in terms of amifostine neuroprotection, but the vibration perception threshold result was based on data from only 14 participants receiving amifostine who completed the post-treatment evaluation and should be regarded with caution. Furthermore the change measured was subclinical. None of the three eligible Ca/Mg trials (or four trials if a single retrospective study was included) described our primary outcome measures. The four Ca/Mg trials included a total of 886 participants. Of the seven eligible glutathione trials (387 participants), one used quantitative sensory testing but reported only qualitative analyses. Four eligible Org 2766 trials (311 participants) employed quantitative sensory testing but reported disparate results; meta-analyses of three of these trials using comparable measures showed no significant vibration perception threshold neuroprotection. The remaining trial reported only descriptive analyses. Similarly, none of the three eligible vitamin E trials (246 participants) reported quantitative sensory testing. The eligible single trials involving acetylcysteine (14 participants), diethyldithiocarbamate (195 participants), oxcarbazepine (32 participants), and retinoic acid (92 participants) did not perform quantitative sensory testing. In all, this review includes data from 2906 participants. However, only seven trials reported data for the primary outcome measure of this review, (quantitative sensory testing) and only nine trials reported our objective secondary measure, nerve conduction test results. Additionally, methodological heterogeneity precluded pooling of the results in most cases. Nonetheless, a larger number of trials reported the results of secondary (non-quantitative and subjective) measures such as the National Cancer Institute Common Toxicity Criteria (NCI-CTC) for neuropathy (15 trials), and these results we pooled and reported as meta-analysis. Amifostine showed a significantly reduced risk of developing neurotoxicity NCI-CTC (or equivalent) ≥ 2 compared to placebo (RR 0.26, 95% CI 0.11 to 0.61). Glutathione was also efficacious with an RR of 0.29 (95% CI 0.10 to 0.85). In three vitamin E studies subjective measures not suitable for combination in meta analysis each favoured vitamin E. For other interventions the qualitative toxicity measures were either negative (N-acetyl cysteine, Ca/Mg, DDTC and retinoic acid) or not evaluated (oxcarbazepine and Org 2766).Adverse events were infrequent or not reported for most interventions. Amifostine was associated with transient hypotension in 8% to 62% of participants, retinoic acid with hypocalcaemia in 11%, and approximately 20% of participantss withdrew from treatment with DDTC because of toxicity.
AUTHORS' CONCLUSIONS
At present, the data are insufficient to conclude that any of the purported chemoprotective agents (acetylcysteine, amifostine, calcium and magnesium, diethyldithiocarbamate, glutathione, Org 2766, oxcarbazepine, retinoic acid, or vitamin E) prevent or limit the neurotoxicity of platin drugs among human patients, as determined using quantitative, objective measures of neuropathy. Amifostine, calcium and magnesium, glutathione, and vitamin E showed modest but promising (borderline statistically significant) results favouring their ability to reduce the neurotoxicity of cisplatin and related chemotherapies, as measured using secondary, non-quantitative and subjective measures such as the NCI-CTC neuropathy grading scale. Among these interventions, the efficacy of only vitamin E was evaluated using quantitative nerve conduction studies; the results were negative and did not support the positive findings based on the qualitative measures. In summary, the present studies are limited by the small number of participants receiving any particular agent, a lack of objective measures of neuropathy, and differing results among similar trials, which make it impossible to conclude that any of the neuroprotective agents tested prevent or limit the neurotoxicity of platinum drugs.
Topics: Antineoplastic Agents; Cisplatin; Humans; Neuroprotective Agents; Peptide Fragments; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic
PubMed: 24687190
DOI: 10.1002/14651858.CD005228.pub4 -
MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy.Cancer May 2014Mucositis is a highly significant, and sometimes dose-limiting, toxicity of cancer therapy. The goal of this systematic review was to update the Multinational... (Review)
Review
BACKGROUND
Mucositis is a highly significant, and sometimes dose-limiting, toxicity of cancer therapy. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for mucositis.
METHODS
A literature search was conducted to identify eligible published articles, based on predefined inclusion/exclusion criteria. Each article was independently reviewed by 2 reviewers. Studies were rated according to the presence of major and minor flaws as per previously published criteria. The body of evidence for each intervention, in each treatment setting, was assigned a level of evidence, based on previously published criteria. Guidelines were developed based on the level of evidence, with 3 possible guideline determinations: recommendation, suggestion, or no guideline possible.
RESULTS
The literature search identified 8279 papers, 1032 of which were retrieved for detailed evaluation based on titles and abstracts. Of these, 570 qualified for final inclusion in the systematic reviews. Sixteen new guidelines were developed for or against the use of various interventions in specific treatment settings. In total, the MASCC/ISOO Mucositis Guidelines now include 32 guidelines: 22 for oral mucositis and 10 for gastrointestinal mucositis. This article describes these updated guidelines.
CONCLUSIONS
The updated MASCC/ISOO Clinical Practice Guidelines for mucositis will help clinicians provide evidence-based management of mucositis secondary to cancer therapy.
Topics: Amifostine; Analgesics; Anti-Infective Agents; Anti-Inflammatory Agents; Anti-Ulcer Agents; Antineoplastic Agents; Cryotherapy; Cytokines; Esophagitis; Evidence-Based Medicine; Humans; Hyperbaric Oxygenation; Intercellular Signaling Peptides and Proteins; Low-Level Light Therapy; Mucositis; Neoplasms; Oral Hygiene; Phototherapy; Proctitis; Protective Agents; Radiation-Protective Agents; Radiotherapy; Stomatitis; Sucralfate
PubMed: 24615748
DOI: 10.1002/cncr.28592 -
Clinical Nutrition (Edinburgh, Scotland) Dec 2013Chemotherapy induced peripheral neuropathy [CIPN] is a common significant and debilitating side effect resulting from the administration of neurotoxic chemotherapeutic... (Review)
Review
Chemotherapy induced peripheral neuropathy [CIPN] is a common significant and debilitating side effect resulting from the administration of neurotoxic chemotherapeutic agents. These pharmaco-chemotherapeutics can include taxanes, vinca alkaloids and others. Moderate to severe CIPN significantly decreases the quality of life and physical abilities of cancer patients and current pharmacotherapy for CIPN e.g. Amifostine and antidepressants have had limited efficacy and may themselves induce adverse side effects. To determine the potential use of nutraceuticals i.e. vitamin E, acetyl-L-carnitine, glutamine, glutathione, vitamin B6, omega-3 fatty acids, magnesium, calcium, alpha lipoic acid and n-acetyl cysteine as adjuvants in cancer treatments a systematic literature review was conducted. Revised clinical studies comprised of randomized clinical trials that investigated the anti-CIPN effect of nutraceuticals as the adjuvant intervention in patients administered chemotherapy. Twenty-four studies were assessed on methodological quality and limitations identified. Studies were mixed in their recommendations for nutraceuticals. Currently no agent has shown solid beneficial evidence to be recommended for the treatment or prophylaxis of CIPN. The standard of care for CIPN includes dose reduction and/or discontinuation of chemotherapy treatment. The management of CIPN remains an important challenge and future studies are warranted before recommendations for the use of supplements can be made.
Topics: Acetylcarnitine; Acetylcysteine; Antineoplastic Agents; Dietary Supplements; Fatty Acids, Omega-3; Glutamine; Glutathione; Humans; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic; Thioctic Acid; Trace Elements; Vitamins
PubMed: 23647723
DOI: 10.1016/j.clnu.2013.04.007 -
Journal of Otolaryngology - Head & Neck... Oct 2012The effectiveness of amifostine in the prevention of cisplatin ototoxicity remains controversial. The objective of this meta-analysis was to determine whether amifostine... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The effectiveness of amifostine in the prevention of cisplatin ototoxicity remains controversial. The objective of this meta-analysis was to determine whether amifostine is successful in preventing ototoxicity secondary to cisplatin chemotherapy.
DESIGN
Meta-analysis.
METHODS
We conducted a systematic review of all randomized, controlled trials using amifostine in patients of all ages receiving cisplatin chemotherapy. Data extraction was performed by two independent reviewers using predefined data fields, including study quality indicators. Heterogeneity was evaluated using the I2 test. The meta-analysis was performed using the random effect method.
MAIN OUTCOME MEASURE
Ototoxicity.
RESULTS
Four randomized, controlled trials were included in this meta-analysis. The odds ratio of grade 2 or greater ototoxicity was 0.54 (95% CI 0.27-1.11), and the odds ratio of grade 3 ototoxicity or greater was 0.78 (95% CI 0.29-2.10). The side effects from amifostine use included hypocalcemia, hypotension, vomiting, and sneezing.
CONCLUSIONS
This meta-analysis reveals a trend toward decreased ototoxicity in patients receiving amifostine infusion prior to receiving cisplatin chemotherapy. However, the results did not reach statistical significance. Further large randomized, controlled trials of amifostine use to prevent cisplatin-induced ototoxicity are needed.
Topics: Amifostine; Antineoplastic Agents; Cisplatin; Ear Diseases; Humans; Neoplasms; Radiation-Protective Agents
PubMed: 23092832
DOI: No ID Found -
Supportive Care in Cancer : Official... Jan 2013The aim of this study was to review the available literature from 1966 until December 31, 2010 and define clinical practice guidelines for the use of amifostine for the... (Review)
Review
PURPOSE
The aim of this study was to review the available literature from 1966 until December 31, 2010 and define clinical practice guidelines for the use of amifostine for the prevention and treatment of oral mucositis in cancer patients.
METHODS
A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. The body of evidence for the use of amifostine, in each cancer treatment setting was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, or no guideline possible.
RESULTS
Thirty papers were reviewed for evidence on amifostine as an intervention for oral mucositis. No guideline was possible for amifostine in any cancer treatment setting due to inadequate and conflicting evidence.
CONCLUSION
Review of the amifostine studies for the prevention and treatment of oral mucositis has found insufficient evidence to support its use in any cancer treatment setting for this purpose. Additional well-designed research is needed to clarify the role of amifostine as an intervention for oral mucositis.
Topics: Administration, Topical; Amifostine; Evidence-Based Medicine; Humans; Infusions, Intravenous; Injections, Subcutaneous; Neoplasms; Practice Guidelines as Topic; Radiation-Protective Agents; Stomatitis
PubMed: 23052919
DOI: 10.1007/s00520-012-1613-6 -
Journal of Cancer Research and Clinical... Dec 2012Factors prediction in the development of radiation pneumonitis (RP) remains unclear. A meta-analysis about this was performed. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Factors prediction in the development of radiation pneumonitis (RP) remains unclear. A meta-analysis about this was performed.
MATERIALS
Articles were searched in February 2012 from PubMed, EMBASE, Cochrane Library and CNKI (Chinese Journal Full-text Database) using the keywords "lung cancer," "radiation pneumonitis" or "radiation lung injury." The outcome was the RP incidence. We pooled the data using RevMan 5.1 software and tested the statistical heterogeneity.
RESULTS
We included the following factors: age, gender, weight loss, smoking history, complications, performance status, pre-radiation therapy (RT) pulmonary function, TNM, histological type, tumor location, pre-RT surgery, RT combined with chemotherapy (RCT), RT/RCT combined with amifostine, plasma end/pre-RT TGF-β1 ratio and irradiation volume. The significant risk factors for RP ≥ grade 2 were patients with chronic lung disease, tumor located in the middle or lower lobe, without pre-RT surgery, RCT, plasma end/pre-RT TGF-β1 ratio ≥1 and gross tumor volume (GTV). Following factors were identified significant for RP, including tumor located not in the upper lobe, smokers, combined with chronic lung diseases or diabetes mellitus, low pre-RT pulmonary function, RCT, RT/RCT without amifostine and plasma end/pre-RT TGF-β1 ratio ≥1. Dose-volume parameters included the average of mean lung dose (MLD) of disease lung, GTV and V (5), V (10) (≥34 %), V (20) (≥25 %), V (30) (≥18 %) of bilateral lung.
CONCLUSIONS
More attention should be paid to the levels of patients' pulmonary function, plasma TGF-β1 and dose-volume histogram (DVH). Rigorous studies are needed to identify the relationship between the above-mentioned factors and RP ≥grade 1 or 3.
Topics: Aged; Case-Control Studies; Cohort Studies; Dose-Response Relationship, Radiation; Female; Humans; Lung Neoplasms; Male; Neoplasm Staging; Radiation Pneumonitis; Radiotherapy Dosage; Randomized Controlled Trials as Topic; Risk Factors; Transforming Growth Factor beta1
PubMed: 22842662
DOI: 10.1007/s00432-012-1284-1 -
The Cochrane Database of Systematic... May 2012Platinum-based therapy, including cisplatin, carboplatin and/or oxaliplatin, is used to treat a variety of paediatric malignancies. Unfortunately, one of the most... (Review)
Review
BACKGROUND
Platinum-based therapy, including cisplatin, carboplatin and/or oxaliplatin, is used to treat a variety of paediatric malignancies. Unfortunately, one of the most important adverse effects is the occurrence of hearing loss or ototoxicity. In an effort to prevent this ototoxicity, different otoprotective medical interventions have been studied.
OBJECTIVES
The primary objective was to assess the efficacy of different otoprotective medical interventions in preventing hearing loss in children with cancer treated with platinum-based therapy. Secondary objectives were to determine possible effects of these interventions on anti-tumour efficacy, toxicities other than hearing loss and quality of life.
SEARCH METHODS
We searched the electronic databases Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4), MEDLINE (PubMed) (1945 to 22 December 2011) and EMBASE (Ovid) (1980 to 22 December 2011). In addition, we handsearched reference lists of relevant articles and the conference proceedings of the International Society for Paediatric Oncology (2006 to 2011), the American Society of Pediatric Hematology/Oncology (2007 to 2011) and the International Conference on Long-Term Complications of Treatment of Children and Adolescents for Cancer (2010). We scanned the International Standard Randomized Controlled Trial Number (ISRCTN) Register and the National Institute of Health Register for ongoing trials (www.controlled-trials.com) (searched on 20 December 2011).
SELECTION CRITERIA
Randomized controlled trials (RCTs) or controlled clinical trials (CCTs) evaluating platinum-based therapy together with an otoprotective medical intervention versus platinum-based therapy with placebo, no additional treatment or another protective medical intervention in children with cancer.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed the study selection, risk of bias assessment of included studies and data extraction, including adverse effects. Analyses were performed according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions.
MAIN RESULTS
We identified two RCTs and one CCT (total number of patients 149) evaluating the use of amifostine versus no additional treatment. Two studies included children with osteosarcoma, the other study included children with hepatoblastoma. Patients received cisplatin only or a combination of cisplatin and carboplatin, either administered intra-arterially or intravenously. All studies had methodological limitations. Unfortunately, pooling of the results of included studies was not possible. However, in all individual studies no significant difference was identified in symptomatic ototoxicity only (that is grade 2 or higher) and combined asymptomatic and symptomatic ototoxicity (that is grade 1 or higher) between children treated with or without amifostine. Only one study, including children with osteosarcoma treated with intra-arterial cisplatin, provided information on tumour response, defined as the number of patients with a good or partial remission. The 'available data' analysis (data were missing for one patient), 'best case scenario' analysis and 'worst case scenario' analysis all showed a difference in favour of amifostine, but this difference was significant only in the 'worst case scenario' analysis (P = 0.04). No information on survival was available for any of the included study populations. Only one study, including children with osteosarcoma treated with intra-arterial cisplatin, provided data on the number of patients with adverse effects other than ototoxicity grade 3 or higher. There was a significant difference in favour of the control group in the occurrence of vomiting grade 3 or 4 (RR 9.04; 95% CI 1.99 to 41.12; P = 0.004). No significant difference was identified between treatment groups for cardiotoxicity and renal toxicity grade 3 or 4. None of the studies evaluated quality of life. No eligible studies were found for possible otoprotective medical interventions other than amifostine and other types of malignancies.
AUTHORS' CONCLUSIONS
At the moment there is no evidence from individual studies in children with osteosarcoma and hepatoblastoma treated with different platinum analogues and dosage schedules which underscores the use of amifostine as an otoprotective intervention as compared to no additional treatment. Since pooling of results was not possible and all studies had serious methodological limitations, no definitive conclusions can be made. It should be noted that 'no evidence of effect', as identified in this review, is not the same as 'evidence of no effect'. Based on the currently available evidence, we are not able to give recommendations for clinical practice. For other possible otoprotective medical interventions and other types of malignancies no eligible studies were identified, so no conclusions can be made about their efficacy in preventing ototoxicity in children treated with platinum-based therapy. More high quality research is needed.
Topics: Adolescent; Amifostine; Antineoplastic Agents; Bone Neoplasms; Carboplatin; Child; Child, Preschool; Cisplatin; Controlled Clinical Trials as Topic; Hearing Loss; Hepatoblastoma; Humans; Infant; Infant, Newborn; Liver Neoplasms; Neoplasms; Osteosarcoma; Protective Agents; Randomized Controlled Trials as Topic; Young Adult
PubMed: 22592737
DOI: 10.1002/14651858.CD009219.pub2 -
The Cochrane Database of Systematic... Jun 2011Anthracyclines are among the most effective chemotherapeutic agents in the treatment of numerous malignancies. Unfortunately, their use is limited by a dose-dependent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Anthracyclines are among the most effective chemotherapeutic agents in the treatment of numerous malignancies. Unfortunately, their use is limited by a dose-dependent cardiotoxicity. In an effort to prevent this cardiotoxicity, different cardioprotective agents have been studied.
OBJECTIVES
The objective of this review was to assess the efficacy of different cardioprotective agents in preventing heart damage in cancer patients treated with anthracyclines.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 10), MEDLINE (1966 to November 2010) and EMBASE (1980 to November 2010) databases. In addition, we handsearched reference lists, conference proceedings of the International Society of Paediatric Oncology (SIOP) and American Society of Clinical Oncology (ASCO) meetings (1998 to 2010) and ongoing trials registers.
SELECTION CRITERIA
Randomised controlled trials (RCTs) in which any cardioprotective agent was compared to no additional therapy or placebo in cancer patients (children and adults) receiving anthracyclines.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed the study selection, risk of bias assessment and data extraction including adverse effects.
MAIN RESULTS
We identified RCTs for the eight cardioprotective agents N-acetylcysteine, phenethylamines, coenzyme Q10, a combination of vitamins E and C and N-acetylcysteine, L-carnitine, carvedilol, amifostine and dexrazoxane (mostly for adults with advanced breast cancer). All studies had methodological limitations and for the first seven agents there were too few studies to allow pooling of results. None of the individual studies showed a cardioprotective effect. The 10 included studies on dexrazoxane enrolled 1619 patients. The meta-analysis for dexrazoxane showed a statistically significant benefit in favour of dexrazoxane for the occurrence of heart failure (risk ratio (RR) 0.29, 95% CI 0.20 to 0.41). No evidence was found for a difference in response rate or survival between the dexrazoxane and control groups. The results for adverse effects were ambiguous. No significant difference in the occurrence of secondary malignancies was identified.
AUTHORS' CONCLUSIONS
No definitive conclusions can be made about the efficacy of cardioprotective agents for which pooling of results was impossible. Dexrazoxane prevents heart damage and no evidence for a difference in response rate or survival between the dexrazoxane and control groups was identified. The evidence available did not allow us to reach any definite conclusions about adverse effects. We conclude that if the risk of cardiac damage is expected to be high, it might be justified to use dexrazoxane in patients with cancer treated with anthracyclines. However, clinicians should weigh the cardioprotective effect of dexrazoxane against the possible risk of adverse effects for each individual patient.
Topics: Anthracyclines; Antibiotics, Antineoplastic; Cardiotonic Agents; Cytoprotection; Heart Diseases; Humans; Neoplasms; Randomized Controlled Trials as Topic; Razoxane
PubMed: 21678342
DOI: 10.1002/14651858.CD003917.pub4 -
The Cochrane Database of Systematic... Apr 2011Treatment of cancer is increasingly more effective but is associated with short and long term side effects. Oral side effects remain a major source of illness despite... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Treatment of cancer is increasingly more effective but is associated with short and long term side effects. Oral side effects remain a major source of illness despite the use of a variety of agents to prevent them. One of these side effects is oral mucositis (mouth ulcers).
OBJECTIVES
To evaluate the effectiveness of prophylactic agents for oral mucositis in patients with cancer receiving treatment, compared with other potentially active interventions, placebo or no treatment.
SEARCH STRATEGY
Electronic searches of Cochrane Oral Health Group and PaPaS Trials Registers (to 16 February 2011), CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to 16 February 2011), EMBASE via OVID (1980 to 16 February 2011), CINAHL via EBSCO (1980 to 16 February 2011), CANCERLIT via PubMed (1950 to 16 February 2011), OpenSIGLE (1980 to 2005) and LILACS via the Virtual Health Library (1980 to 16 February 2011) were undertaken. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information.
SELECTION CRITERIA
Randomised controlled trials of interventions to prevent oral mucositis in patients receiving treatment for cancer.
DATA COLLECTION AND ANALYSIS
Information regarding methods, participants, interventions, outcome measures, results and risk of bias were independently extracted, in duplicate, by two review authors. Authors were contacted for further details where these were unclear. The Cochrane Collaboration statistical guidelines were followed and risk ratios calculated using random-effects models.
MAIN RESULTS
A total of 131 studies with 10,514 randomised participants are now included. Overall only 8% of these studies were assessed as being at low risk of bias. Ten interventions, where there was more than one trial in the meta-analysis, showed some statistically significant evidence of a benefit (albeit sometimes weak) for either preventing or reducing the severity of mucositis, compared to either a placebo or no treatment. These ten interventions were: aloe vera, amifostine, cryotherapy, granulocyte-colony stimulating factor (G-CSF), intravenous glutamine, honey, keratinocyte growth factor, laser, polymixin/tobramycin/amphotericin (PTA) antibiotic pastille/paste and sucralfate.
AUTHORS' CONCLUSIONS
Ten interventions were found to have some benefit with regard to preventing or reducing the severity of mucositis associated with cancer treatment. The strength of the evidence was variable and implications for practice include consideration that benefits may be specific for certain cancer types and treatment. There is a need for further well designed, and conducted trials with sufficient numbers of participants to perform subgroup analyses by type of disease and chemotherapeutic agent.
Topics: Antineoplastic Agents; Candidiasis, Oral; Humans; Neoplasms; Oral Ulcer; Randomized Controlled Trials as Topic; Stomatitis
PubMed: 21491378
DOI: 10.1002/14651858.CD000978.pub5