Palifermin: new drug. Prevention of oral mucositis: inappropriate evaluation

(1) Patients treated with high-dose chemotherapy combined with total body irradiation (myeloablative therapy) often develop oral mucositis. Prevention is based mainly on sucking ice during chemotherapy. (2) Palifermin is a growth factor marketed for the prevention of severe oral mucositis in adults with malignant haemopathies who are receiving myeloablative therapy followed by peripheral stem cell autografting. (3) Palifermin has not been compared with sucking ice, despite the efficacy of this simple treatment. (4) In a randomised placebo-controlled double-blind trial involving 212 adult patients treated with high-dose chemotherapy and total body irradiation, palifermin reduced the incidence of severe oral mucositis (63% versus 98%) and its duration (about 3 days versus 9 days). The myeloablative regimen used in this trial is not that commonly used in Europe. The efficacy of palifermin during less aggressive regimens, which cause less severe oral mucositis, is not known. (5) The main adverse events noted in clinical trials were erythema and cutaneous oedema. It is not known whether palifermin increases the long-term risk of cancer. (6) Treatment with palifermin is expensive, 4800.00 euros in France); the optimal dosing schedule is not known and the unit dose chosen by the manufacturer is wastefully large. (7) In practice, it remains to be demonstrated that palifermin is more effective than simply sucking ice.     

Palifermin: a keratinocyte growth factor that reduces oral mucositis after stem cell transplant for haematological malignancies

Mucositis occurs in ≤ 98% of patients undergoing stem cell transplant for haematological malignancies and is associated with significant morbidity and mortality. Patients with severe mucositis have more pain, more difficulty with daily activities such as talking and eating, and are more likely to have bacteraemia. Palifermin is a keratinocyte growth factor that has been shown to decrease severity and duration of mucositis with a concurrent decrease in patient-reported symptoms and use of narcotics and total parenteral nutrition. Research is ongoing into palifermin’s potential ability to decrease graft-versus-host disease and improve reconstitution of functional T lymphocytes after allogeneic stem cell transplant, to hasten wound healing and to reduce mucositis following external beam radiation therapy in solid tumour patients.     

Palifermin: a keratinocyte growth factor that reduces oral mucositis after stem cell transplant for haematological malignancies

Mucositis occurs in < or = 98% of patients undergoing stem cell transplant for haematological malignancies and is associated with significant morbidity and mortality. Patients with severe mucositis have more pain, more difficulty with daily activities such as talking and eating, and are more likely to have bacteraemia. Palifermin is a keratinocyte growth factor that has been shown to decrease severity and duration of mucositis with a concurrent decrease in patient-reported symptoms and use of narcotics and total parenteral nutrition. Research is ongoing into palifermin's potential ability to decrease graft-versus-host disease and improve reconstitution of functional T lymphocytes after allogeneic stem cell transplant, to hasten wound healing and to reduce mucositis following external beam radiation therapy in solid tumour patients.     

Chemotherapy-induced oral mucositis: new approaches to prevention and management

Oral mucositis is a common and significant toxicity of cancer chemotherapy. It is under-reported and not well treated, particularly in patients that receive high-dose therapy with an autologous or allogenic stem cell transplant. Two recently published retrospective analyses of patient complaints following stem cell transplantation have identified oral mucositis as the worst toxicity reported by patients, and what is more important is that patients indicated that oncology healthcare team members do a poor job of managing and providing methods of symptom relief. Twenty percent of patients surveyed indi-cated they received no symptom relief at all.     

Chemotherapy-induced oral mucositis: new approaches to prevention and management

Oral mucositis is a common and significant toxicity of cancer chemotherapy. It is under-reported and not well treated, particularly in patients that receive high-dose therapy with an autologous or allogenic stem cell transplant. Two recently published retrospective analyses of patient complaints following stem cell transplantation have identified oral mucositis as the worst toxicity reported by patients, and what is more important is that patients indicated that oncology healthcare team members do a poor job of managing and providing methods of symptom relief. Twenty percent of patients surveyed indicated they received no symptom relief at all.     

Chemotherapy-induced oral mucositis. Prevention and management

Oral mucositis is a frequent and potentially severe complication of chemotherapy which has a considerable impact on patient quality of life. While the management of other chemotherapy-related toxicities has improved, the incidence of mucositis is increasing. A critical review of the literature published between 1985 and 1999 reveals very few strategies or agents with proven efficacy, leaving few recommendations for the standard care in the prevention and treatment of mucositis at this time. Recommendations that can be made include: reducing patient risk factors, implementing proven preventative interventions such as utilising oral ice chips with fluorouracil chemotherapy, and optimising supportive care practices individualised to the patients' needs and symptoms. Progress in understanding the pathophysiology of mucositis at the molecular level has led to the evaluation of a number of new investigational agents, specifically those directed to the epithelial mucosa, such as mitogens and epithelial growth factors. These appear to be very promising in preclinical studies. Randomised clinical trials with these agents may finally demonstrate an impact on the clinical practice of mucositis management in the coming years.     

化疗后口腔黏膜炎治疗的研究进展

口腔黏膜炎是肿瘤化疗过程中出现的常见不良反应，黏膜溃疡引起口腔局部剧烈的疼痛，黏膜炎症增加全身严重感染的风险，最终导致抗肿瘤治疗的中断，影响了化疗方案的效果。基于局部和全身治疗的干预思路，利用药物和非药物治疗的多种手段，可降低口腔黏膜炎的发生率或严重程度。     

核黄素防治放射性口腔黏膜炎的疗效观察

目的观察核黄素磷酸钠联合康复新液用于鼻咽癌放射性口腔黏膜炎的预防及治疗效果。方法选取我院经病理确诊的74例初诊放疗的鼻咽癌患者,随机分为试验组及对照组。试验组37例:核黄素磷酸钠联合康复新液。具体用药:核黄素磷酸钠注射液30 mg+生理盐水100 m L,放疗期间1次/d静点;康复新液,放疗期间3次/d,10 m L/次,于口中含服3~5 min后缓慢咽下。对照组:康复新液单药,用药剂量及用法与试验组相同。结果 74例均纳入分析,试验组患者Ⅱ级以上放射性口腔黏膜炎的发生率明显低于对照组(37.8%vs.67.6%,P=0.019);试验组患者主要为轻度疼痛(67.6%),而对照组以中度疼痛为主(56.8%),两组疼痛程度比较,差异有统计学意义(P=0.035)。本研究中未观察到重度药物相关不良反应,提示药物安全性良好。结论核黄素磷酸钠联合康复新液防治放射性口腔黏膜炎的效果确切、安全,值得临床推广。     

Chemotherapy- and radiotherapy-induced oral mucositis: review of preventive strategies and treatment

Oral mucositis is a frequently encountered and potentially severe complication associated with administration of chemotherapy and radiotherapy. Although many pharmacologic interventions have been used for the prevention and treatment of oral mucositis, there is not one universally accepted strategy for its management. Most preventive and treatment strategies are based on limited, often anecdotal, clinical data. Basic oral hygiene and comprehensive patient education are important components of care for any patient with cancer at risk for development of oral mucositis. Nonpharmacologic approaches for the prevention of oral mucositis include oral cryotherapy for patients receiving chemotherapy with bolus 5-fluorouracil, and low-level laser therapy for patients undergoing hematopoietic stem cell transplantation. Chlorhexidine, amifostine, hematologic growth factors, pentoxifylline, glutamine, and several other agents have all been investigated for prevention of oral mucositis. Results have been conflicting, inconclusive, or of limited benefit. Treatment of established mucositis remains a challenge and focuses on a palliative management approach. Topical anesthetics, mixtures (also called cocktails), and mucosal coating agents have been used despite the lack of experimental evidence supporting their efficacy. Investigational agents are targeting the specific mechanisms of mucosal injury; among the most promising of these is recombinant human keratinocyte growth factor.     

A rat model against chemotherapy plus radiation-induced oral mucositis

ObjectivesPresent study was aimed at developing an experimental model of oral mucositis in rats using a combination of chemotherapeutic agent and radiation.Study designFemale Wistar rats (150–200 g) were divided into 3 groups (n = 6). Rats in group 1 (normal control) and group 2 (mucositis control) were treated with vehicle. Rats in group 3 were treated with l-glutamine (1 g/kg, p.o.; 15 days) before and after mucositis induction. Oral mucositis was induced by busulfan (6 mg/kg, p.o.; 4 days) and the tongue exposed to infrared (IR) radiation of intensity 40 mV/cm² for 5 s on the 1st, 4th and 10th days of challenge using a tail flick apparatus. Parameters monitored were body weight, food intake, blood count and survival. Oral mucositis score (OMS) was recorded daily. Histological changes of the irradiated tongue were assessed by hematoxylin and eosin staining.ResultsBusulfan and IR radiation significantly reduced body weight and food intake of the mucositis control group as compared to normal control. Clear ulceration of the tongue reflected in the OMS. Histopathology of the tongue revealed intense lymphocytic infiltration, decreased thickness of squamous epithelial cell layer, decrease in number of blood vessels, and necrosis of cells along with pseudo-membrane formation in the mucositis control group. These findings suggested that oral mucositis was successfully induced and treatment with l-glutamine partially reversed these conditions.ConclusionOral mucositis was established successfully in rats by the combination of chemotherapeutic agent and IR radiation. This may be a useful model for screening drugs in the treatment of oral mucositis.     

银翘散加减方护理放射性口腔黏膜炎应用

目的探讨银翘散合五味消毒饮加减方在鼻咽癌患者放疗后口腔黏膜反应的应用效果。方法将85例患者随机分为观察组43例,常规护理组42例。观察组采用银翘散合五味消毒饮加减方治疗,对照组采用常规护理方法,分别评价治疗后护理效果。结果治疗8周后两组患者放疗后口腔黏膜反应程度,差异具有统计学意义(P<0.05)。观察组患者放疗后口腔黏膜反应情况优于常规护理组,其持续时间较短,差异具有统计学意义(P<0.05),反应程度较轻(P<0.05),产生副作用的例数更少,差异具有统计学意义(P<0.05)。结论应用银翘散合五味消毒饮加减方能够有效地减轻鼻咽癌放疗患者的口腔黏膜反应、减轻痛苦并提高生活质量。     

Pharmacotherapy for the management of cancer regimen-related oral mucositis

Introduction: Oral mucositis is a frequent and devastating toxicity secondary to cancer treatment, which may affect 20–40% of patients receiving conventional chemotherapy and 60–85% of patients undergoing hematopoietic stem cell transplantation. The pathobiology of mucositis includes a complex cascade of biologic events in which pro-inflammatory cytokines, ROS, second messengers, and the oral microbiome contribute to tissue damage of the oral mucosa. Management strategies to oral mucositis secondary to chemotherapy include preventative measures and therapeutic approaches.

Area covered: A literature search of published animal and clinical studies was perform to review the epidemiology, pathophysiology and treatment options for cancer regimen-induced mucositis. We also discuss new data coming from recent pertinent clinical trials.

Expert opinion: Mucositis is one of the most common debilitating toxicities secondary to cancer treatment and can adversely affect patients’ quality of life. Epidemiological data for mucositis are often under-reported. Research efforts have shown that genetics plays a major role in the development of this toxicity. Although few therapeutic agents are available, several promising drugs are under investigations.     

Section Reviews: Biologicals & Immunologicals: Pharmacological attenuation of chemotherapy-induced oral mucositis

Mucositis is a common, dose-limiting complication in patients receiving cancer chemotherapy, which derives from cytotoxic insult to the oral epithelial cell population. While a number of treatments which palliate the symptoms associated with ulcerative mucositis are available, they do not effectively treat the underlying mucosal injury. Recently, therapeutic approaches utilising cytokines to stimulate healing or prevent damage to the oral mucosa have been described. Here we review current progress in reducing the incidence and severity of oral mucositis in cancer patients. The circumvention of oral and gastrointestinal mucositis should allow dose or schedule intensification, with a goal to effect increases in long-term survival in patients with cancers responsive to high-dose or accelerated-cycle chemotherapy.     

自制漱口液在化疗患者口腔黏膜炎中的应用

目的 探讨自制漱口液治疗化疗引起的口腔黏膜炎的效果.方法 将71例发生口腔黏膜炎的化疗患者随机分为观察组（36例,采用自制漱口液）和对照组（35例,用生理盐水）进行对比研究.结果 观察组治愈率为88.87％,对照组治愈率为51.42％；观察组有效率为100％,对照组有效率为82.86％；观察组比对照组平均治愈时间明显缩短,差异均具有统计学意义（P＜0.05）.结论 自制漱口液治疗口腔黏膜炎明显优于生理盐水.     

氟康唑治疗急性放射性口腔粘膜炎继发的真菌感染

目的 :研究头颈部肿瘤放射治疗中急性放射性口腔粘膜反应与真菌感染的关系及氟康唑治疗的有效性。方法 :71例口腔粘膜受到大面积照射的肿瘤病人 :男性 4 2例 ,女性 2 9例 ;年龄 52a±s 4 1a( 11～ 76a) ,在病人的口腔粘膜反应最严重的时候 ,做口腔粘膜真菌学检查 ,32例有真菌感染的病人 ,用氟康唑胶囊 10 0mg ,po ,qd× 5d或氟康唑注射液 150mg ,iv ,gtt× 3d治疗。结果 :真菌的检出率为 4 5% ,以白念珠菌感染为主。有真菌感染和无真菌感染的 2组病人 ,在急性放射性粘膜反应上差异有显著意义 (P <0 .0 5) ;有真菌感染的病人用氟康唑治疗 ,治疗前后的粘膜反应差异有显著意义 (P<0 .0 5)。结论 :严重的急性放射性粘膜反应与真菌感染有密切的关系 ;有真菌感染的放射性口腔粘膜反应用氟康唑治疗可以明显减轻放射性粘膜反应     

Evaluation of topical external medicine for 5-fluorouracil-induced oral mucositis in hamsters

Oral ulcerative mucositis is a common and painful toxicity associated with chemotherapy for cancer. Current treatment for chemotherapy-induced oral mucositis is largely palliative, and no adequate treatment with conclusive evidence exists. The purpose of this study was to evaluate the potential effectiveness of the topical external medicines used in clinical settings, and the authors investigated the effects of 1% azulene ointment, 0.12% dexamethasone ointment, and polaprezinc-sodium alginate suspension on an animal model for oral mucositis induced by chemotherapy. Oral mucositis was induced in hamsters through a combination treatment of 5-fluorouracil and mild abrasion of the cheek pouch. Each drug was administered topically to the oral mucosa of hamsters, and the process of healing of damaged oral mucositis was examined by measuring the size of the mucositis. Azulene ointment did not reduce the size of the mucositis compared with the vaseline-treated control group. Polaprezinc-sodium alginate suspension significantly improved the recovery from 5-fluorouracil-induced damage. In contrast, local treatment with dexamethasone exacerbated the mucositis markedly. These results suggested the healing effect of polaprezinc-sodium alginate suspension and the risk of steroids to severe oral mucositis induced by chemotherapy.