Efficacy of Oral Cryotherapy in the Prevention of Oral Mucositis Associated with Cancer Chemotherapy: Systematic Review with Meta-Analysis and Trial Sequential Analysis

Background: This review aimed to evaluate the efficacy of oral cryotherapy in the prevention of chemotherapy-induced oral mucositis using meta-analysis and trial sequential analysis, as well as to assess the quality of the results by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Methods: A comprehensive search of three databases including Medline, Embase and Central was performed to identify randomized controlled trials that used oral cryotherapy for the prevention of chemotherapy-induced oral mucositis. The primary outcome was the incidence of oral mucositis for trials employing oral cryotherapy as the intervention for the prevention of oral mucositis. The meta-analysis was performed using the random-effects model and random errors of the meta-analyses were detected by trial sequential analysis. Results: A total of 14 RCTs with 1577 participants were included in the present meta-analysis. Patients treated with oral cryotherapy were associated with a significantly lower risk of developing oral mucositis of any grade (risk ratio (RR), 0.67 (95% CI: 0.56–0.81, p < 0.05)). Findings from the subgroup analyses showed that oral cryotherapy significantly reduced the risk of oral mucositis in patients undergoing bone marrow transplantation (RR 0.69, CI: 0.54–0.89, p < 0.05) as well as chemotherapy (RR 0.66, CI: 0.58–0.75, p < 0.05). Findings from the trial sequential analysis suggested that the evidence on oral cryotherapy as a preventive intervention for oral mucositis in patients with solid malignancies receiving conventional chemotherapy was conclusive. Conclusion: Oral cryotherapy is effective in preventing oral mucositis in patients undergoing chemotherapy for the management of solid malignancies. The use of oral cryotherapy in preventing oral mucositis in bone marrow transplantation settings showed promising efficacy, but the evidence is not conclusive and requires more high-quality randomized controlled trials.     

Effect of granulocyte-macrophage colony-stimulating factor on chemotherapy-induced oral mucositis in non-neutro-penic cancer patients

The aim of this study was to assess prospectively the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the management of chemotherapy-induced oral mucositis in non-neutropenic cancer patients. In a prospective open study, 30 cancer patients with chemotherapy-induced, neutropenia-independent oral mucositis were treated with GM-CSF (Schering Plough Corp, Kenilworth, NJ) prepared as a mouthwash solution (5-10 μg ml^-1). GM-CSF was administered within 24 hours of occurrence of oral mucositis x 4 to 6 times daily. Systemic GM-CSF was not permissible. Oral mucositis was graded according to the modified Radiation Therapy Oncology Group criteria. Six patients were subsequently excluded as they experienced neutropenia during GM-CSF therapy. The remaining 24 patients were all evaluable. Most patients had either Grade 3 or 4 gross (76%) or functional (54%) mucositis. The mean ± SEM gross oral mucositis scores for all 24 patients combined decreased from 3.08 ± 0.18 at baseline to 2.04 ± 0.19(p < 0.0001) after 2 days, 0.92 ± 0.16(p < 0.0001) after 5 days, and 0.25 ± 0.09(p < 0.0001) after 10 days of therapy. Likewise, the mean ± SEM functional oral mucositis scores decreased from 2.71 ± 0.18 at baseline to 1.58 ± 0.19(p < 0.0001) after 2 days, 0.75 ± 0.16(p < 0.0001) after 5 days, and 0.17 ± 0.08(p < 0.0001) after 10 days of therapy. The duration of severe oral mucositis was also shortened as Grade 0 or 1 (gross mucositis score) was evident in seven (29%), 20 (83%), and 24 (100%) patients by the 2nd, 5th, and 10th day of therapy, respectively. Similarly, Grade 0 or 1 (functional mucositis score) reported in 13 (54%), 19 (79%), and 24 (100%) by the 2nd, 5th, and 10th day of therapy respectively. It was found that GM-CSF mouthwash as used in this study has a significant recuperative efficacy on the severity, morbidity, and duration of chemotherapy-induced oral mucositis. A large randomized, placebo-controlled study is warranted to ascertain that benefit and determine the optimal dosages and schedule.     

Antiseptic effect of a novel alcohol-free mouthwash: a convenient prophylactic alternative for high-risk patients

We developed an efficacious and non-irritant mouthwash that is alcohol-free and that has a low concentration of chlorhexidine, in order to be used for preventing oral cavity infections in immunocompromised and cancer patients. The novel mouthwash solution was tested for its antimicrobial efficacy against both free floating (planktonic) and the biofilm forms of Candida albicans. The solution was also tested against Klebsiella pneumoniae, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA), using a modification of a previously published method. The activity of the novel mouthwash was also compared with that of three commercially available mouthwashes. The experimental mouthwash showed efficacy against C. albicans, both in free-floating form and in biofilm. With higher concentration of chlorhexidine, the solution was also efficacious in inhibiting the growth of K. pneumoniae, P. aeruginosa, and MRSA. The antiseptic activity of the alcohol-free mouthwash against other bacterial organisms and C. albicans was comparable to other commercially available alcohol-based mouthwash solutions. A novel alcohol-free mouthwash solution, that has low concentration of chlorhexidine, showed antiseptic effect against planktonic and biofilm forms of C. albicans and against K. pneumoniae, P. aeruginosa, and MRSA.     

Radiation-induced mucositis: a randomized clinical trial of micronized sucralfate versus salt & soda mouthwashes

Oral mucositis is one of the major toxicities caused by radiation therapy (RT) treatments to the head and neck. The clinical efficacy of sucralfate (Carafate R) mouthwash for head and neck cancer patients (HNC) is not consistent across studies. In this study, it was hypothesized that if the particles in the original sucralfate suspension were micronized (i.e., ≤25 microns) then the coating action of the mouthwash in the oral cavity would be enhanced. The purpose of this pilot study was to compare the efficacy of micronized sucralfate (Carafate R) mouthwash and salt & soda mouthwash in terms of the severity of the mucositis, the severity of mucositis-related pain, and the time required to heal RT-induced mucositis in patients with HNC. Severe mucositis and related pain can interfere with the ingestion of food and fluids, so patients' body weights were measured as well. All patients in this randomized clinical trial carried out a systematic oral hygiene protocol called the PRO-SELF: Mouth Aware (PSMA) Program. Patients who developed RT-induced mucositis anytime during their course of RT were randomized to one of the two mouthwashes and followed to the completion of RT and at one month following RT. Two referral sites were used for the study. Repeated measures occurred with the following instruments/variables: MacDibbs Mouth Assessment and weight. Demographic, disease, and cancer treatment information was also obtained. Thirty patients successfully completed the study. The typical participant was male (70%), married/partnered (70%), White (63%), not working or retired (73%), and had an average of 14.5 years of education (SD=3.7). T-tests and Chi-square analyses with an alpha set at 0.05 were used to compare differences between the two mouthwashes. No significant differences were found in the number of days to onset of mucositis (i.e., 16±8.4 days). When patients had their worst MacDibbs score, (i.e., the most severe mucositis), there were no significant differences between the mouthwashes as to MacDibbs score, the RT dose received, or ratings of pain (upon swallowing). Similarly, at the end of RT, no significant differences were found between mouthwashes as to MacDibbs scores or ratings of pain (upon swallowing). At the one-month follow-up assessment no significant differences were found between the mouthwashes in MacDibbs scores or pain ratings (upon swallowing). The analysis of the efficacy of the two mouthwashes revealed no significant differences in the time to heal (in days) from the RT-induced mucositis. The findings from this trial provide important clinical information regarding cost analysis of RT mucositis management. Given that there is no significant difference in efficacy between micronized sucralfate and salt & soda, use of the less costly salt & soda is prudent and cost-effective.     

Evaluation of an oral care protocol intervention in the prevention of chemotherapy-induced oral mucositis in paediatric cancer patients

Oral mucositis is the most frequent and severe complication of chemotherapy in children with cancer that can aggravate the child's clinical condition and increase the risk of infection. This prospective comparative study was designed to determine the effectiveness of a preventive oral care protocol in reducing chemotherapy-induced oral mucositis in children with cancer. During an 8-month period, 42 children aged 6 to 17 years with haematological malignancies or solid tumours were evaluated. The 21 children who were included in the first 4-month period of the study constituted the control group. Another 21 children were enrolled in the subsequent 4 months and were assigned to the experimental group, in which they were given an oral care protocol intervention. The oral care protocol consisted of tooth brushing, 0.2% chlorhexidine mouth rinse and 0.9% saline rinse. Children in both groups were evaluated twice a week for 3 weeks. The incidence of ulcerative lesions, severity of oral mucositis and the related pain intensity were used as the main outcome variables. A 38% reduction in the incidence of ulcerative mucositis was found in children using the oral care protocol compared with children in the control group. The severity of oral mucositis (P=0.000002) and the related pain (P=0.0001) were significantly reduced with the intervention. These results support the preventive use of the oral care protocol in paediatric cancer patients who undergo chemotherapy for cancer treatment.     

Decrease of duration and symptoms in chemotherapy-induced oral mucositis by topical GM-CSF: results of a prospective randomised trial

We have conducted a prospective controlled randomised clinical study testing for the efficacy of topical GM-CSF (molgramostim), as compared to the combined topical use of an antiseptic agent (povidone-iodine) and amphotericin B (AA) in patients with chemotherapy-induced mucositis World Health Organization (WHO) grades I-III. 31 patients (17 females, 14 males) developing oral mucositis following the administration of 5-fluorouracil (5-FU)-based chemotherapy were entered into the present trial. 15 patients were randomised to receive GM-CSF mouthwashes, whereas 16 patients were randomised into the control arm to receive AA. Reported history (P=0.6109) and grading of oral mucositis (2.1+/-0.7, respectively; P=0.9867) were balanced and equally distributed between the two groups. The mean size of lesions of oral mucositis was 1.5+/-0.6 cm (range: 0.7-2.5 cm) in the GM-CSF group and 1.2+/-0.5 cm (range: 0.5-2.5 cm) in the AA group (P=0.08), respectively. The mean number of oral mucositis lesions was 1.9+/-1.1 (range: 1-4) in the GM-CSF group and 2.1+/-1.2 (range: 1-4) in the AA group (P=0.63), respectively. None of the patients had previously received colony stimulating factors either topically or systemically. Treatment for oral mucositis was initiated on day 2.7+/-1.2 (range: day 1-8) after onset of symptoms in the GM-CSF group and on day 1.8+/-1.4 (range: day 1-3; P=0.11) in the AA group. The topical application of GM-CSF resulted in a significantly shorter duration and quicker resolution of oral mucositis, as compared to AA including both, pretreatment plus treatment periods (5.3+/-2.5 versus 8.1+/-1.5 days; P=0.0008) as well as the necessary duration of treatment needed until complete remission of lesions (2.8+/-0.7 versus 6.3+/-1.1 days; P<0.0001). A systemic effect of topical GM-CSF upon the number of peripheral blood leukocytes or granulocytes was excluded. We conclude that the topical application of GM-CSF by mouthwash significantly abbreviated the duration and relieved patients from symptoms of chemotherapy-induced mucositis and was superior to the topical application of AA.     

A controlled evaluation of an allopurinol mouthwash as prophylaxis against 5-fluorouracil-induced stomatitis

Pursuant to a promising report suggesting that an allopurinol mouthwash could have a protective effect against 5-fluorouracil (5-FU)-induced stomatitis, the authors performed a randomized, placebo-controlled, double-blind, crossover study. Seventy-seven patients, receiving their first 5-day course of chemotherapy with 5-FU +/- leucovorin, were assigned to use a mouthwash containing 20 mg of allopurinol or a placebo. The mouthwash was administered every hour for four doses commencing with each chemotherapy dose. The severity of subsequent mucositis was graded (on a 0-4 scale) by the attending physician and also by a patient-completed questionnaire. There was trend toward less mucositis in the placebo group with mean physician-judged mucositis scores of 1.3 for placebo and 1.8 for allopurinol (P = 0.07) and mean patient-judged mucositis scores of 1.5 for placebo and 1.9 for allopurinol (P = 0.15). There were no substantial differences in mucositis attributable to the two mouthwashes in the patients who crossed-over on their second cycle of chemotherapy. These data demonstrate that the tested allopurinol mouthwash regimen does not offer any protective effect against 5-FU-induced mucositis.     

Prophylaxis with GM-CSF mouthwashes does not reduce frequency and duration of severe oral mucositis in patients with solid tumors undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue: a double blind, randomized, placebo-controlled study.

BACKGROUND: The aim of this study was to evaluate the effectiveness of granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwashes in the prevention of severe mucositis induced by high doses of chemotherapy. PATIENTS AND METHODS: Ninety consecutive patients affected by solid tumors and undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue were randomized to receive placebo versus GM-CSF mouthwash 150 micro g/day. Patients were stratified on the basis of the conditioning treatment and the consequent different risk of severe oral mucositis. Treatment was administered from the day after the end of chemotherapy until the resolution of stomatitis and/or neutrophil recovery. RESULTS: The statistical analyses were intention-to-treat and involved all patients who entered the study. The severity of stomatitis was evaluated daily by the physicians according to National Cancer Institute Common Toxicity Criteria. Both study and control groups were compared with respect to the frequency [30% versus 36%, chi(2) exact test, not significant (NS)] and mean duration (4.8 +/- 4.7 versus 4.4 +/- 2.7 days, t-test, NS) of severe stomatitis (grade > or =3). Oral pain was evaluated daily by patients themselves by means of a 10 cm analog visual scale: the mean (+/- standard error of the mean) maximum mucositis scores were 4.8 +/- 3.5 versus 4.2 +/- 3.5 cm (t-test, NS). Furthermore, 15/46 patients in the study group (33%) and 19/44 patients in the control group experienced pain requiring opioids (chi(2) exact test, NS). CONCLUSION: We did not find any evidence to indicate that prophylaxis with GM-CSF mouthwash can help to reduce the severity of mucositis in the setting of the patients we studied.     

Comparison of granulocyte-macrophage colony-stimulating factor and sucralfate mouthwashes in the prevention of radiation-induced mucositis: a double-blind prospective randomized phase III study

PURPOSE: To compare granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwashes with sucralfate mouthwashes in the prevention of radiation-induced mucositis. METHODS AND MATERIALS: Forty patients with radically operated head-and-neck cancer were randomly allocated to use either GM-CSF (n = 21) or sucralfate (n = 19) mouthwashes during postoperative radiotherapy (RT). All patients received conventionally fractionated RT to a total dose of 50-60 Gy in 2-Gy daily fractions during 5-6 weeks to the primary site and regional lymphatics. A minimum of 50% of the oral cavity and oropharyngeal mucosa was included in the clinical target volume. GM-CSF mouthwashes consisted of 37.5 microg GM-CSF and sucralfate mouthwashes of 1.0 g of sucralfate distilled in water. Both washes were used 4 times daily, beginning after the first week of RT and continued to the end of the RT course. Symptoms related to radiation mucositis and body weight, serum prealbumin level, and blood cell counts were monitored weekly. RESULTS: Oral mucositis tended to be less severe in the GM-CSF group (p = 0.072). Complete (n = 1) or partial (n = 4) healing of mucositis occurred during the RT course in 5 patients (24%) in the GM-CSF group and in none of the patients in the sucralfate group (p = 0.049). Patients who received GM-CSF had less mucosal pain (p = 0.058) and were less often prescribed opioids for pain (p = 0.042). Three patients in the sucralfate group needed hospitalization for mucositis during RT compared with none in the GM-CSF group. Four patients (21%) in the sucralfate group and none in the GM-CSF group required an interruption in the RT course (p = 0.042). No significant differences in weight, prealbumin level, or blood cell count were found between the groups, and both mouthwashes were well tolerated. CONCLUSION: GM-CSF mouthwashes may be moderately more effective than sucralfate mouthwashes in preventing radiation-induced mucositis and mucositis-related pain, and their use may lead to less frequent RT course interruptions from mucositis. The present findings need to be confirmed before adopting GM-CSF mouthwashes in routine clinical use.     

Studies on the prevention of 5-fluorouracil-induced oral mucositis

Oral mucositis is a major toxic effect related to 5-fluorouracil (5-FU) therapy. Clinical studies have attempted to identify an effective antidote for this untoward side effect. Early pilot studies suggested that an allopurinol mouthwash could lessen 5-FU-induced mucositis. However, a randomized, double-blinded, placebo-controlled crossover study did not suggest that an allopurinol mouthwash had any prophylactic value in this clinical situation. An ongoing, randomized clinical protocol is testing cryotherapy as a method of inhibiting 5-FU-induced stomatitis. No clinically appropriate prophylactic measure for preventing 5-FU-induced mucositis has been found to date.     

Double-blind, placebo-controlled, randomized study of chlorhexidine prophylaxis for 5-fluorouracil-based chemotherapy-induced oral mucositis with nonblinded randomized comparison to oral cooling (cryotherapy) in gastrointestinal malignancies

BACKGROUND: The purpose was to evaluate prevention of oral mucositis (OM) using chlorhexidine compared with placebo and with oral cooling (cryotherapy) during fluorouracil (5-FU)-based chemotherapy in gastrointestinal (GI) cancer. METHODS: Patients with previously untreated GI cancer receiving bolus 5-FU/leucovorin chemotherapy were randomized to chlorhexidine mouthrinse 3 times a day for 3 weeks (Arm A), double-blind placebo (normal saline) with the same dose and frequency (Arm B), or cryotherapy with crushed ice 45 minutes during chemotherapy (Arm C). Patients self-reported on severity (CTC-grading) and duration of OM. RESULTS: Among 225 patients randomized, 206 answered the questionnaire (70, 64, and 63 patients in Arms A, B, and C, respectively) and were well balanced with respect to diagnoses, stage, age, sex, smoking habits, and performance status. Mucositis grade 3-4 occurred more frequently in Arm B (33%) than in A (13%, P< .01) and C (11%, P< .005). Duration was significantly longer in B than in both A (P= .035) and C (P= .003). CONCLUSIONS: The frequency and duration of OM are significantly improved by prophylactic chlorhexidine and by cryotherapy. The latter is easy and inexpensive but has limited use, as it is drug- and schedule-dependent. The current study is the first double-blind randomized evaluation of prophylactic chlorhexidine in a large adult patient population with solid tumors receiving highly OM-inducing chemotherapy. A role for chlorhexidine in the prevention of OM is suggested, which should be evaluated further.     

康复新联合rhG-CSF防治放射性口腔炎的临床观察

目的:观察康复新液联合rhG-CSF（重组人粒细胞集落刺激因子）局部应用对放射性口腔炎的防治效果。方法:将46例经病理确诊的头颈部恶性肿瘤患者随机分为两组,实验组(23例)采用康复新液联合rhG-CSF稀释后含漱,对照组(23例)采用rhG-CSF稀释后含漱,两组均采用常规分割方式放疗。采用全美放射肿瘤治疗协作组(RTOG)急性放射性黏膜炎的分级标准,观察放射性口腔炎的发生时间、发生率及严重程度。结果:实验组与对照组放射性口腔炎平均发生时间分别为(28．57±1．93)d 及(19．57±1．95)d,P＜0．001。放射性口腔炎总发生率分别为65.22%及91.30%,P=0．032。2级以上放射性口腔黏膜损伤发生率分别为17.39%及47.83%,P=0.028。结论:康复新液联合rhG-CSF能够延迟放射性口腔炎出现时间,降低放射性口腔的发生率,并减轻其损伤程度。     

Randomized DoubleBlind PlaceboControlled Trial of Propolis for Oral Mucositis in Patients Receiving Chemotherapy for Head and Neck Cancer

Background: Propolis based preparations have a wide range of applications in various specialties of dentistry. The aim of this clinical trial was to test the efficacy of propolis as a mouthwash in the reduction of chemotherapy induced oral mucositis (OM) in a single center. Materials and Methods: In this randomised, controlled study patients undergoing chemotherapy were included consecutively and randomised to an experimental group receiving propolis mouthwash (n 20) and a control group receiving diluted water (n20). Oral mucositis, erythema and eating and drink ability were assessed at baseline and after 3 and 7 days using the World Health Organization (WHO) scale and the oral mucositis assessment scale (OMAS). Results: There were significant differences in OM, wound and erythema in propolis group compared to placebo, but no significant difference in eating and drink ability. However, it was interesting that 65% of the patients in the propolis group were completely healed at day 7 of the trial. No significant adverse events were reported by the patients. Conclusions: This study found that oral care with propolis as mouthwash for patients undergoing chemotherapy is an effective intervention to improve oral health. Our findings shouldlencourage health practitioners to apply propolis mouth rinse for the oral care of patients under chemotherapy.     

Phase I study of transforming growth factor-beta3 mouthwashes for prevention of chemotherapy-induced mucositis.

The purpose of this study was to establish the safety and tolerability of recombinant transforming growth factor-beta3 (TGF-beta3; CGP 46614) mouthwashes intended for prevention of chemotherapy-induced mucositis. Local effects were especially analyzed by objective and subjective measurements of mucositis. Secondary aims were analysis of potential systemic exposure and development of anti-TGF-beta3-antibodies. Eleven breast cancer patients received chemotherapy with 1.5 g/m2 cyclophosphamide i.v., 80 mg/m2 epirubicin i.v., and 1.0 g/m2 5-fluorouracil i.v. (n = 8) or 1.6 g/m2 carboplatin i.v., 480 mg/m2 thiotepa i.v., and 6 g/m2 cyclophosphamide i.v. divided over 4 days (n = 3). TGF-beta3 mouthwashes (10 ml; provided by Novartis, Basel, Switzerland) were administered for 4 days, four times a day, starting 1 day before chemotherapy. The dose was escalated in following patients from 25 microg/ml (n = 3) to 50 microg/ml (n = 3) and 100 microg/ml (n = 5). Clinically, the mucosa was scored objectively and according to WHO criteria. The percentage of viable oral epithelial cells was determined by trypan blue dye exclusion. Morphology of cells was assessed in buccal smears. Plasma samples were collected for determination of TGF-beta3 levels and anti-TGF-beta3-antibodies. Adverse events were recorded by the patient in a diary. Mouthwashes with TGF-beta3 were well tolerated. Three patients scored for mucositis > grade 0 (WHO grading criteria). The percentage of viable oral epithelial cells in patients treated with 1.5 g/m2 cyclophosphamide i.v., 80 mg/m2 epirubicin i.v., and 1.0 g/m2 5-fluorouracil i.v. was stable, whereas in patients treated with 1.6 g/m2 carboplatin i.v., 480 mg/m2 thiotepa i.v., and 6 g/m2 cyclophosphamide i.v. divided over 4 days, an increase was observed. The morphology of buccal cells showed a transient shift from mature to immature cells in the first week. Neither systemic absorption of TGF-beta3 nor development of TGF-beta3-antibodies was observed. TGF-beta3 mouthwashes were well tolerated and deserve further study in preventing chemotherapy-induced mucositis.     

Updated clinical practice guidelines for the prevention and treatment of mucositis

Considerable progress in research and clinical application has been made since the original guidelines for managing mucositis in cancer patients were published in 2004, and the first active drug for the prevention and treatment of this condition has been approved by the United States Food and Drug Administration and other regulatory agencies in Europe and Australia. These changes necessitate an updated review of the literature and guidelines. Panel members reviewed the biomedical literature on mucositis published in English between January 2002 and May 2005 and reached a consensus based on the criteria of the American Society of Clinical Oncology. Changes in the guidelines included recommendations for the use of palifermin for oral mucositis associated with stem cell transplantation, amifostine for radiation proctitis, and cryotherapy for mucositis associated with high-dose melphalan. Recommendations against specific practices were introduced: Systemic glutamine was not recommended for the prevention of gastrointestinal mucositis, and sucralfate and antimicrobial lozenges were not recommended for radiation-induced oral mucositis. Furthermore, new guidelines suggested that granulocyte-macrophage-colony stimulating factor mouthwashes not be used for oral mucositis prevention in the transplantation population. Advances in mucositis treatment and research have been complemented by an increased rate of publication on mucosal injury in cancer. However, additional and sustained efforts will be required to gain a fuller understanding of the pathobiology, impact on overall patient status, optimal therapeutic strategies, and improved educational programs for health professionals, patients, and caregivers. These efforts are likely to have significant clinical and economic impact on the treatment of cancer patients. Cancer 2007;109:820-31. (c) 2007 American Cancer Society.     

Correlation between the in vivo and in vitro antimicrobial properties of commercially available mouthwash preparations.

The effectiveness of six commercially available mouthwashes against common buccal organisms was studied. The minimum inhibitory concentrations (MIC) for two of the studied mouthwashes (Corsodyl and Oraldene) against buccal organisms were determined in Todd Hewitt medium with or without 5% serum. The concentration of the active substance in these two mouthwashes was in excess of the corresponding MIC. When the medium was supplemented with serum, lower MIC values were observed. Kill-time determinations, used at half the concentration of the normal preparation, revealed a rapid lethal effect for all tested mouthwashes. The slowest lethal effect was observed with Fluocaril mouthwash. When mouthwashes were tested in volunteers, an immediate significant fall in salivary bacterial counts was produced by all except Fluocaril. With the latter mouthwash the decrease was significant 2-30 minutes after rinsing. The bacterial levels returned to pre-rinse levels after 30 minutes for Listerine, after 90 minutes for both Oraldene and Mint and after 180 minutes for Corsodyl, Fluocaril and Sansilla mouthwashes. The results indicate that there is a good correlation between in vivo efficacy and in vitro determination of all mouthwash preparations.     

头颈部肿瘤化疗引起口腔黏膜炎的危险因素分析

目的:探讨影响头颈部肿瘤化疗引起口腔黏膜炎的危险因素。方法:研究对象为2011年5月-2013年6月我市三甲医院315例头颈部接受化疗的肿瘤患者,分析引起头颈部肿瘤化疗患者口腔黏膜炎症的影响因素。结果:随着患者年龄的增大,口腔黏膜炎的发病率有逐渐升高的趋势,有吸烟史的患者以及有义齿的患者口腔黏膜的发病率较高,性别对于口腔黏膜炎症的发病率没有影响;口腔pH、白细胞数与患者口腔黏膜炎症的发病率没有显著性的关系（P＜0.05）,含5-FU、口腔疾患、预防漱口等与患者口腔黏膜炎症的发病率有显著性的关系（P＜0.05);具有恶心、呕吐患者的口腔黏膜炎症的发病率较高,使用抗生素患者的口腔黏膜炎症的发病率要显著性低于未使用抗生素的患者,具有焦虑抑郁的患者发生口腔黏膜炎症的发病率会显著性的增加,随着住院天数的增加,患者发生口腔黏膜炎症的发病率会显著性的升高,两组比较均具有显著性的差异（P＜0.05）。结论:年龄、口腔疾患、含5-FU、抗生素、住院天数、焦虑抑郁等与头颈部的肿瘤化疗患者引起口腔黏膜炎症的发生率有一定的相关性。     

Safety and Efficacy of a Mouth-Rinse with Granulocyte Colony Stimulating Factor in Patients with Chemotherapy-Induced Oral Mucositis

Objective: To assess the safety and effectiveness of a mouth-rinse with G-CSF (JiSaiXin, produced by NCPC Biotechnology Co., Ltd) in treating patients with chemotherapy-induced oral mucositis (CIM). Method: A consecutive cohort of patients with advanced cancers and CIM were treated with mouth-rinse G-CSF. All chemotherapy for patients with advanced cancers was adopted from regimens suggested by NCCN guidelines. The mouth-rinse with G-CSF at a dose of 150-300ug plus 100ml-500ml normal saline was started from the time of oral mucositis was confirmed and continuously used for at least 7 days as one course. After at least two courses of treatment, safety and efficacy were evaluated. Results: There were 7 female and 7 male patients with advanced cancer and CIM recruited into this study, including 5 with colorectal, 2 with lung, 1 patient with gastric, 1 with cervical and 1 with pancreatic cancer, as well as 2 patients with diffuse large B cell lymphomas, 1 with nasopharyngeal and 1 with gastric cancer. The median age was 57 (41-79) years. Grade 1 to 2 myelosuppression was observed in 3/14 patients, and Grade 4 myelosuppression in 1/14. Adverse effects on the gastrointestinal tract were documented in 5/14 patients, and were Grade 1 to Grade 3. No treatment related death was documented. Regarding CIM, the median response time to mouth rinse of G-CSF was 2 (1-5) days, and all patients with CIM demonstrated a positive response. Conclusions: Mouth-rinse with G-CSF proved to be safe and effective in treating patients with advanced cancers and CIM. However, further randomized controlled studies should be conducted to clarify the effectiveness of this treatment with other lesions.     

Chemotherapy-induced stomatitis and diarrhea

Chemotherapy-induced mucositis is a clinically important and sometimes dose-limiting toxicity of cancer treatment, including standard-dose chemotherapy, high-dose chemotherapy and chemoradiotherapy. Consequently, dose reductions or treatment delays resulting from mucositis may impair treatment effectiveness. Symptoms are oral mucositis, dysphagia, abdominal pain and diarrhea, depending on the affected site. Although the underlying pathobiology of oral mucositis has been considerably elucidated over the past decade, there are few interventions for the prevention or treatment validated by randomized trials. The most commonly accepted intervention is basic oral care. Diarrhea is most common in patients treated with irinotecan and in some cases, life-threatening. No definitive interventions for the prevention of diarrhea exist, but there is evidence that loperamide and octreotide are effective for chemotherapy-induced diarrhea. In future, there is a need for well designed trials, preferably including a placebo or no treatment control, validating more effective interventions for managing chemotherapy- induced mucositis.     

Correlation Between the In Vivo And In Vitro Antimicrobial Properties of Commercially Available Mouthwash Preparations

Summary

The effectiveness of six commercially available mouthwashes against common buccal organisms was studied. The minimum inhibitory concentrations (MIC) for two of the studied mouthwashes (Corsodyl and Oraldene) against buccal organisms were determined in Todd Hewitt medium with or without 5% serum. The concentration of the active substance in these two mouthwashes was in excess of the corresponding MIC. When the medium was supplemented with serum, lower MIC values were observed. Kill-time determinations, used at half the concentration of the normal preparation, revealed a rapid lethal effect for all tested mouthwashes. The slowest lethal effect was observed with Fluocaril mouthwash.

When mouthwashes were tested in volunteers, an immediate significant fall in salivary bacterial counts was produced by all except Fluocaril. With the latter mouthwash the decrease was significant 2-30 minutes after rinsing. The bacterial levels returned to pre-rinse levels after 30 minutes for Listerine, after 90 minutes for both Oraldene and Mint and after 180 minutes for Corsodyl, Fluocaril and Sansilla mouthwashes. The results indicate that there is a good correlation between in vivo efficacy and in vitro determination of all mouthwash preparations.