利妥昔单抗联合化疗治疗回盲部弥漫大B细胞淋巴瘤的临床分析

目的探讨利妥昔单抗(美罗华)联合化疗治疗回盲部弥漫大B细胞淋巴瘤的疗效及毒副作用。方法 6例经病理检查证实为回盲部弥漫大B细胞淋巴瘤患者,5例采用利妥昔单抗联合CTNP方案化疗,1例采用CTNP方案化疗,每21天为1个周期,观察治疗前后的毒副作用及疗效。结果 5例利妥昔单抗联合化疗治疗的患者有4例达完全缓解,1例达部分缓解;另1例单纯化疗患者死于疾病进展。结论利妥昔单抗联合化疗治疗回盲部弥漫大B细胞淋巴瘤可取得较好疗效,对于高龄患者利妥昔单抗无需减量,但需注意调整化疗剂量,并监测不良反应。     

沙利度胺联合利妥昔单抗治疗CLL/SLL的近期疗效

目的探讨沙利度胺联合利妥昔单抗治疗慢性淋巴细胞白血病/小淋巴细胞淋巴瘤(CLL/SLL)的临床疗效及安全性。方法对25例CLL患者进行前瞻性研究,采用简单随机分组法,分为沙利度胺联合利妥昔单抗方案(TR)治疗组12例,利妥昔单抗联合氟达拉滨+环磷酰胺方案(FCR)对照组13例,评估患者的近期疗效和不良反应。结果经2个疗程、4个疗程治疗后,FCR组ORR明显高于TR组(P<0.05);在第6个疗程后,TR组与FCR组ORR率差异无统计学意义。TR组总体不良反应发生率明显低于FCR组(P<0.05)。结论沙利度胺联合利妥昔单抗治疗CLL/SLL,起效时间长,但近期疗效理想,不良反应轻。     

利妥昔单抗治疗弥漫大B淋巴瘤的毒副作用及其护理

目的：探讨利妥昔单抗治疗弥漫大 B 淋巴瘤的毒副作用及其护理。方法选取安徽医科大学第一附属医院肿瘤内科2012年7月—2013年12月收治的32例弥漫大 B 淋巴瘤患者,给予利妥昔单抗联合 CHOP 化疗,观察疗效及根据毒副作用给予的针对性护理结果。结果32例患者中3例患者在治疗期间因病情发展而停止应用利妥昔单抗治疗,退出研究,有效率为58.62％;毒副作用发生率为82.76％。结论临床上应用利妥昔单抗治疗肿瘤时,其毒副作用发生率较高,应充分评估其可能发生的毒副作用,针对毒副作用可能带来的风险,制定护理措施。     

血浆置换联合利妥昔单抗治疗初诊特发性血栓性血小板减少性紫癜的临床分析

目的分析血浆置换联合利妥昔单抗治疗初诊特发性血栓性血小板减少性紫癜(TTP)临床特征、治疗效果及生存情况。方法回顾性分析4例采用血浆置换联合利妥昔单抗方案治疗的初诊特发性TTP患者的临床资料。结果 3例患者有典型的"五联征",1例患者表现为微血管病性溶血性贫血、血小板减少和中枢神经系统症状。4例患者初诊时ADAMTS13无活性,ADAMTS13抗体阳性。4例患者治疗后获得临床缓解,治疗过程中无利妥昔单抗输注反应,无严重感染事件发生。中位随访29个月,患者均未复发,长期存活。结论 4例初诊特发性TTP患者在血浆置换基础上联用利妥昔单抗安全、有效、耐受性良好。     

利妥昔单抗联合CHOP方案治疗NHL的临床疗效评价

目的:探讨利妥昔单抗联合环磷酰胺、阿霉素、长春新碱、强的松(CHOP)方案治疗非霍奇金淋巴瘤(NHL)的疗效及安全性。方法:62例NHL患者,其中32例接受利妥昔单抗联合CHOP方案治疗者为治疗组;30例接受CHOP方案治疗者为对照组。每周期21d,共进行6个疗程。结果:治疗组与对照组总有效率分别为75.00%、60.00%(P<0.05);2组毒副作用基本相似(P>0.05);治疗组的生活质量改善情况明显高于对照组(P<0.05)。结论:利妥昔单抗联合CHOP方案对NHL患者有较好疗效,且化疗药物的毒副作用未见增加。     

HBsAg阳性淋巴瘤患者应用利妥昔单抗联合化疗后肝功能损害分析

目的探讨在抗病毒治疗的前提下应用利妥昔单抗(商品名:美罗华)联合化疗对乙肝表面抗原阳性(HBsAg+)淋巴瘤患者肝功能的影响。方法回顾性分析2001年7月至2011年6月病理确诊B细胞非霍奇金淋巴瘤伴HBsAg阳性的39例住院患者的临床资料。其中男31例,女8例,中位年龄47(21-83)岁。所有患者均接受利妥昔单抗联合化疗。早期有7例患者未进行抗病毒治疗,另32例患者每日口服拉米夫定100mg或恩替卡韦500μg,化疗后定期监测HBV-DNA。结果应用利妥昔单抗联合化疗治疗B细胞淋巴瘤107例。其中HBsAg阳性者39例,占36.4%。病毒高拷贝数8例(HBV DNA>104copy.mL-1),未抗病毒治疗的病人肝功能损害发生率为57.1%,有4例出现急性暴发性肝衰竭,3例死亡(死亡率高达42.9%),抗乙肝病毒治疗的有32例,有12例出现肝功能损害,发生率为37.5%,明显低于未抗病毒治疗者,抗病毒治疗的32例中包括乙肝大三阳6例及病毒高拷贝数8例(4例乙肝大三阳),乙肝大三阳中有4例发生肝功能损害,病毒高拷贝数患者中有4例出现肝功异常,大多为Ⅰ~Ⅱ度肝功能损害。结论在有效抗病毒及激素减量使用的同时,密切监测乙肝DNA,并严格遵循抗病毒药物的停药时间,HBsAg阳性淋巴瘤患者接受利妥昔单抗联合化疗是安全的。     

利妥昔单抗联合调整剂量EPOCH方案治疗胃肠道弥漫大B细胞淋巴瘤的可行性观察

目的:分析与探讨利妥昔单抗联合调整剂量EPOCH方案治疗胃肠道弥漫大B细胞淋巴瘤的可行性.方法:选取累及胃肠道的弥漫大B细胞淋巴瘤患者26例,分析发病经过、临床特点、病理特点以及预后判断,运用利妥昔单抗联合调整剂量的EPICH(R-DA-EPOCH)治疗方案进行治疗,观察化疗后的治疗反应并随访转归情况.结果:本次研究中3例接受R-DA-EPOCH方案治疗后得到了良好治疗结果.结论:采取利妥昔单抗联合调整剂量EPOCH方案治疗胃肠道弥漫大B细胞淋巴瘤具有一定可行性,近期疗效良好,但本次研究样本量过少,需将样本量扩大对远期疗效进行判断.     

延续护理在利妥昔单抗联合短疗程、高强度化疗治疗Burkitt's淋巴瘤/白血病中的应用研究

目的:探究延续护理在利妥昔单抗联合短疗程、高强度化疗治疗Burkitt’s淋巴瘤/白血病中的应用效果.方法:选取2018年9月～2019年9月本院收治的100例Burkitt’s淋巴瘤/白血病患者作为研究对象,按照随机数字表法将其分为观察组和对照组,各50例.在利妥昔单抗联合短疗程、高强度化疗的基础上,对照组给予常规护...     

利妥昔单抗治疗儿童难治性自身免疫性溶血性贫血2例并文献复习

目的:探讨利妥昔单抗治疗儿童难治性自身免疫性溶血性贫血(AIHA)的疗效、毒副作用。方法:(1)总结2例难治性AIHA患儿的临床表现、实验室检查结果及使用利妥昔单抗治疗前后的情况。(2)对2例患儿选用利妥昔单抗治疗(每次375 mg/m2,每周1次,共4次),随访利妥昔单抗使用后CD20+细胞、血红蛋白等的变化情况,探讨利妥昔单抗治疗儿童AIHA的疗效;同时观察发热、皮疹、感染等毒副作用。结果:2例患儿诊断AIHA后均首先选用糖皮质激素治疗,初期都能显效,但不能长期维持,需长期依赖激素及输血。使用利妥昔单抗治疗后,2例患儿均能显效,其中1例治愈,1例病情反复,最终死于严重贫血。结论:尽管糖皮质激素是治疗AIHA的一线药物,但激素依赖或难治性病例较常见,因此利妥昔单抗已逐渐成为儿童难治性AIHA安全有效的二线治疗药物。     

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利妥昔单抗联合化疗治疗慢性淋巴细胞白血病有效 单克隆抗体利妥昔单抗（rituximab）加入氟达拉滨＋环磷酰胺一线化疗方案是否改善慢性淋巴细胞白血病患者的临床转归？此项随机开放性Ⅲ期临床试验进行了探讨。身体健康良好、年龄在30～81Y、CD20＋、未治的慢性淋巴细胞白血病患者,     

美罗华治疗侵袭性B细胞淋巴瘤疗效观察

目的：探讨美罗华治疗侵袭性B细胞淋巴瘤的临床疗效及优越性。方法：回顾性分析我院78例侵袭性B细胞NHL患者治疗情况,其中39例为观察组采用美罗华联合CHOP化疗方案,39例为对照组采用CHOP化疗方案,观察两组近期疗效及不良反应情况,并进行对比分析。结果：观察组CR率和有效率（CR＋PR）率分别为79.49%和92.31%,明显高于对照组的53.85%和64.10%,组间比较差异有统计学意义（P〈0.05）;两组不良反应发生率比较差异无统计学意义（P〉0.05）。结论：含美罗华的联合化疗方案可提高侵袭性B细胞淋巴瘤治疗的临床疗效,且不会增加其不良反应,是目前侵袭性B细胞淋巴瘤治疗的一种较佳方案,值得临床推广应用。     

肺癌患者化疗中不同的用药方式的临床评价

目的 是探讨肺癌患者化疗中不同的用药方式的副作用以及临床疗效的评价.方法 选取2010年1月至2011年1月本医院的50名住院接受EP(顺铂,依托泊苷)方案化疗前四个疗程的肺小细胞癌患者,进行回顾性分析EP方案中顺铂的不同用药途径在肺癌(SCLC) 治疗中的近期疗效和不良反应.结果 1次组和分次组近期有效率分别68%和72%,两组比较差异无统计学意义(P>0.05); 1次组不良反应(乏力、食欲减退、恶心、呕吐、脱发、口腔溃疡及发热)发生率均明显高于分次组(P<0.05).结论 分次组明显改善肺癌化疗患者的睡眠质量及化疗不良反应发生情况,使患者的生活质量得到明显提高,顺铂分次用药能减轻化疗相关毒副作用,提高患者的生活质量.     

Opportunities and obstacles of targeted therapy and immunotherapy in small cell lung cancer

Abstract

Small cell lung cancer (SCLC) is an aggressive malignant tumour which accounts for approximately 13–15% of all newly diagnosed lung cancer cases. To date, platinum-based chemotherapy are still the first-line treatments for SCLC. However, chemotherapy resistance and systemic toxicity limit the long-term clinical outcome of first-line treatment in SCLC. Recent years, targeted therapy and immunotherapy have made great breakthrough in cancer therapy, and researchers aim to exploit both as a single agent or in combination with chemotherapy to improve the survival of SCLC patients, but limited effectiveness and the adverse events remain the major obstacles in the treatment of SCLC. To overcome these challenges for SCLC therapies, prevention and early diagnosis for this refractory disease is very important. At the same time, we should reveal more information about the pathogenesis of SCLC and the mechanism of drug resistance. Finally, new treatment strategies should also be taken into considerations, such as repurposing drug, optimising of targets, combination therapy strategies or prognostic biomarkers to enhance therapeutic effects and decrease the adverse events rates in SCLC patients. This article will review the molecular biology characteristics of SCLC and discuss the opportunities and obstacles of the current therapy for SCLC patients.     

靶向药物联合化疗治疗晚期非小细胞肺癌的临床分析

目的 分析研究靶向药物联合化疗治疗晚期非小细胞肺癌（NSCLC）的疗效.方法 选取2011-2012年我院收治的晚期NSCLC患者46例,将其随机划分为两组.甲组采用常规的化疗药物治疗,乙组在给予常规化疗基础上使用靶向药物治疗,比较两组治疗效果.结果 甲组临床疗效优于乙组,差异有统计学意义（P＜0.05）;两组患者血红蛋白、血小板、白细胞下降及皮疹、消化道反应发生率比较差异无统计学意义（P＞0.05）.结论 给予晚期NSCLC患者采用靶向药物联合化疗治疗,可显著提高临床治疗效果.     

唑来膦酸联合化疗治疗晚期非小细胞肺癌骨转移的临床思路总结

目的 探讨唑来膦酸联合化疗治疗晚期非小细胞肺癌骨转移的临床效果.方法 选取我院于2011年7月至2013年7月收治的42例晚期非小细胞肺癌骨转移患者作为研究对象,按照随机分组方式将患者分为观察组21例和对照组21例,对照组给予常规化疗措施,观察组在化疗基础上给予唑来膦酸治疗,对两组患者NRS、KPS水平进行测评,评价两种治疗方式的效果.结果 观察组骨转移灶完全缓解7例,部分缓解9例,稳定4例,恶化1例,综合有效率（完全缓解＋部分缓解）为76.19％,对照组完全缓解4例,部分缓解3例,稳定5例,恶化9例,综合有效率为33.33％,两组患者综合有效率对比具有显著的统计学差异（P＜0.01）;两组患者经治疗后NRS、KPS均有不同程度改善,相比治疗前差异有统计学意义（P＜0.05）,观察组改善更为明显,相比对照组差异有统计学意义（P＜0.05）.结论 唑来膦酸联合化疗治疗晚期非小细胞肺癌骨转移疗效显著,对于缓解患者疼痛、改善患者预后具有重要的临床意义.     

Rituximab maintenance therapy for follicular lymphoma: no better than watchful waiting

Chemotherapy is the first-choice treatment for patients with advanced follicular lymphoma (Ann Arbor stage III or IV) who qualify for therapy, but there is no consensus protocol. Adding rituximab (Mabthera, Roche) to chemotherapy moderately improves survival time. Rituximab is now authorised for long-term maintenance therapy in patients with follicular lymphoma in whom first-line chemotherapy induces a response. Clinical evaluation of rituximab in this setting is based on two unblinded randomised trials comparing rituximab maintenance therapy with watchful waiting in 1193 and 401 patients. Neither trial showed that rituximab had an impact on mortality or quality of life. Rituximab prolonged progression-free survival, based on unblinded assessment of radiological, laboratory or clinical criteria. These trials suffer from biases that make it difficult to interpret the results, including the lack of blinding, premature termination and too short follow-up in the larger trial, and in the other trial, heterogeneous patient recruitment and use of a different dose regimen from that recommended in the summary of product characteristics. Both trials confirmed the adverse effect profile of rituximab, which includes haematological disorders, infections, and cardiac and digestive disorders. These adverse effects are severe in about 7% of patients. There is also a riskof musculoskeletal and neuropsychiatric disorders. Questions still persist abouta possible oncogenic effect. In practice, the benefits of long-term rituximab maintenance therapy after a first line of chemotherapy remain to be demonstrated in terms of the length or quality of survival in patients with follicular lymphoma, while adverse effects are noteworthy. Pending further data, rituximab should only be used in clinical trials in this specific setting.     

利妥昔单抗联合化疗治疗弥漫性大B细胞淋巴瘤的临床观察

目的：评价利妥昔单抗联合化疗治疗弥漫性大B细胞淋巴瘤（DLBCL）的疗效及安全性.方法：116例DLBCL患者接受利妥昔单抗联合化疗方案,中位治疗4.73个疗程.初治DLBCL患者112例,其中R-CHOP 87例,R-CHOP样29例;26例在化疗中进展.采用Cheson标准及WHO标准评估疗效及不良反应.结果：116例患者全部进行疗效评价,总体客观有效率为75％ （87/116）,CR ＋CRu为34例（29.31％）,PR为53例（45.69％）,SD为12例（10.34％）,PD为17例（14.66％）.其中1例患者在挽救方案获得缓解后,接受自体干细胞支持下的超大剂量化疗.主要不良反应为骨髓抑制,消化道反应,轻度肝损伤,首次输注反应2例.中位随访52.3（3.2～86.5）月,6例死于肿瘤进展,2例死于骨髓抑制后合并重度感染.中位生存期60.54月（3.2～86.5）,其中1、3、5年总生存率分别为81％、63％、52％,无病生存期1、3、5年总生存率分别为76％、52％、47％.在影响疗效相关因素分析中,IPI评分Ann、Arbor分期和LDH水平为影响患者化疗效果的相关因素（P＜0.05）.结论：利妥昔单抗联合治疗DLBCL的疗效确切,不良反应可以耐受,效果与文献报道一致.     

新辅助化疗联合保乳术治疗乳腺癌的临床效果分析

目的分析新辅助化疗联合保乳术治疗乳腺癌的临床效果。方法收集2010年7月-2012年7月本院收治的60例乳腺癌患者的临床资料,按照治疗方法的不同分为治疗组与对照组,每组各30例。对照组患者采取传统乳腺癌根治术治疗,治疗组患者采取新辅助化疗联合保乳术治疗,分析两组患者的临床疗效。结果治疗组患者的总有效率为90.00%,明显高于对照组的63.33%,差异有统计学意义（P〈0.05）。治疗组患者的手术时间、术中出血量、住院时间明显少于对照组,差异有统计学意义（P〈0.05）。两组患者的复发率及远处转移率比较,差异无统计学意义（P〉0.05）。结论新辅助化疗联合保乳术治疗乳腺癌的创伤较小、功能恢复快、住院时间短,可改善患者的预后,值得临床推广。     

Rituximab: a review of its use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia

Rituximab is an anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with various lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukaemia (CLL). While the optimal use of the drug in many clinical settings has yet to be clarified, two pivotal trials have established rituximab as a viable treatment option in patients with relapsed or refractory indolent NHL, and as a standard first-line treatment option when combined with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy in elderly patients with diffuse large B-cell lymphoma (the most common type of aggressive NHL). The former was a noncomparative trial in relapsed indolent NHL (follicular and small lymphocytic subtypes) with clinical responses achieved in about half of patients treated with rituximab 375 mg/m(2) intravenously once weekly for 4 weeks, which was similar to some of the most encouraging results reported with traditional chemotherapeutic agents. The latter was a randomised comparison of eight cycles of CHOP plus rituximab 375 mg/m(2) intravenously (one dose per cycle) versus CHOP alone in previously untreated elderly patients (60 to 80 years of age) with diffuse large B-cell lymphoma. In this pivotal trial, 2-year event-free and overall survival were significantly higher with rituximab plus CHOP, and there was no increase in clinically significant adverse effects compared with CHOP alone. Treatment with rituximab is generally well tolerated, particularly in terms of adverse haematological effects and serious or opportunistic infections relative to standard chemotherapy. Infusion-related reactions occur in the majority of patients treated with rituximab; these are usually mild to moderate flu-like symptoms that decrease in frequency with subsequent infusions. In approximately 10% of patients, however, severe infusion-related reactions develop (e.g. bronchospasm, hypotension). These reactions are usually reversible with appropriate interventions and supportive care but there have been rare reports of fatalities. CONCLUSIONS: Clinical trials with rituximab indicate that the drug has broad application to B-cell malignancies, although further clarification is needed to determine its optimal use in many of these clinical settings. Importantly, rituximab in combination with CHOP chemotherapy has emerged as a new treatment standard for previously untreated diffuse large B-cell lymphoma, at least in elderly patients. Compared with conventional chemotherapy, rituximab is associated with markedly reduced haematological events such as severe neutropenia, as well as associated infections. Rituximab may be particularly suitable for elderly patients or those with poor performance status, and its tolerability profile facilitates its use in combination with cytotoxic drugs. PHARMACODYNAMIC PROPERTIES: Rituximab is a mouse/human chimaeric IgG(1)-kappa monoclonal antibody that targets the CD20 antigen found on the surface of malignant and normal B lymphocytes. Although treatment with rituximab induces lymphopenia in most patients, typically lasting about 6 months, a full recovery of B lymphocytes in the peripheral blood is usually seen 9-12 months after therapy, as CD20 is not expressed on haematopoietic stem cells. CD20 is, however, expressed on >90% of B-cell non-Hodgkin's lymphomas (NHL) and to a lesser degree on B-cell chronic lymphocytic leukaemia (CLL) cells.Although not fully elucidated, the cytotoxic effects of rituximab on CD20-positive malignant B cells appears to involve complement-dependent cytotoxicity, complement-dependent cellular cytotoxicity, antibody-dependent cellular cytotoxicity and induction of apoptosis. In addition, in vitro data indicate that rituximab sensitises tumour cells to the effects of conventional chemotherapeutic drugs. PHARMACOKINETIC PROPERTIES: Serum rituximab concentrations increased in proportion to dose across a wide range of single- and multiple-dose intravenous regimens in patients with B-cell NHL. When administll NHL. When administered at a dose of 375 mg/m(2) once weekly for 4 weeks in a pivotal trial in patients with relapsed or refractory indolent B-cell NHL (follicular or small lymphocytic subtypes), peak serum concentrations essentially doubled from the first (239.1 mg/L) to the fourth (460.7 mg/L) infusion, while elimination half-life (t(1/2)) increased from 76.3 to 205.8 hours (3.2 to 8.6 days). The concomitant increase in serum rituximab concentrations and t(1/2) with each successive infusion may be due, at least in part, to the elimination of circulating CD20-positive B cells and reduction or saturation of CD20-binding sites after the initial infusions of rituximab. The pharmacokinetic properties of rituximab are also characterised by wide inter-individual variability, and serum drug concentrations that are correlated with clinical response. Although pharmacokinetic data are limited in patients with aggressive forms of NHL, such as diffuse large B-cell lymphoma, rituximab appears to have a similar pharmacokinetic profile in these patients to that in patients with indolent B-cell NHL. The pharmacokinetics of rituximab are also reported to be similar whether the drug is administered with or without cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy. THERAPEUTIC USE: A number of studies have demonstrated efficacy of intravenous rituximab in patients with various lymphoid malignancies of B-cell origin, including indolent (e.g. follicular lymphoma) and aggressive (e.g. diffuse large B-cell lymphoma) forms of NHL, and CLL, but the drug has not yet been approved for use in CLL, and approved indications in NHL vary between countries. In the US, for example, rituximab is available for the treatment of patients with low-grade or follicular, relapsed or refractory, CD20-positive B-cell NHL. In Europe, the drug has similar approval for relapsed or refractory follicular NHL as in the US, but has also been approved for use in combination with CHOP chemotherapy for the most common aggressive form of NHL (CD20-positive, diffuse large B-cell lymphoma). Rituximab was approved for these indications primarily on the basis of results from two pivotal trials. In Japan, rituximab has been approved for indolent B-cell NHL and mantle cell lymphoma (an aggressive form of B-cell NHL), primarily on the basis of results of a Japanese phase II trial. Indolent NHL: Results of several studies evaluating rituximab 375 mg/m(2) once weekly for 4 weeks in patients with indolent forms of B-cell NHL (primarily follicular and small lymphocytic lymphomas) showed objective response (OR) rates ranging from approximately 40-60% in those receiving the drug for relapsed or refractory indolent B-cell NHL, and slightly higher (50-70%) for those receiving rituximab as first-line therapy. In a pivotal trial in 166 patients with relapsed or refractory low-grade or follicular B-cell NHL, intent-to-treat (ITT) analysis showed an OR rate of 48%, and a projected median time to progression of 13 months.Encouraging data are also emerging on the use of rituximab in combination with chemotherapeutic agents (e.g. CHOP, fludarabine-containing regimens) or other drugs (e.g. interferon-alpha2a) in previously untreated patients with indolent forms of B-cell NHL (primarily follicular and small lymphocytic subtypes). Rates for OR were consistently around 95%, with the majority being complete responses (CRs). Follow-up data from a study in 40 patients with low-grade or follicular B-cell NHL treated with rituximab plus CHOP as first-line therapy showed that responses were durable with a progression-free survival and median duration of response >5 years.Bcl-2 gene rearrangement (t14;18) occurs in malignant cells in up to 85% of patients with follicular lymphoma, and minimal residual disease in peripheral blood and bone marrow can be monitored using polymerase chain reaction (PCR). In several studies assessing blood and/or bone marrow, rituximab has achieved molecular response (conversion from PCR-positive to PCR-negative bcl-2 status) in at least half of the patients. Aggressive NHL: Studies with rituximab as monotherapy in aggressive B-cell NHL, a potentially curable disorder, have generally been restricted to patients with relapsed or recurrent disease, since CHOP has traditionally been the standard first-line treatment regimen. However, promising results from phase II monotherapy studies prompted further clinical investigation of rituximab in conjunction with chemotherapy. Thus, most studies with rituximab in patients with aggressive forms of B-cell NHL have involved combination therapy, including a pivotal randomised trial comparing eight cycles of standard CHOP therapy plus rituximab 375 mg/m(2) (one dose per cycle) versus CHOP alone in 399 previously untreated elderly patients (60-80 years of age) with diffuse large B-cell lymphoma. Results of the pivotal trial showed a clear advantage for rituximab plus CHOP versus CHOP in terms of event-free survival (primary endpoint) at 2 years (57% vs 38%, p < 0.001). Overall survival at 2 years (70% vs 57%, p < 0.01) and CR rate (76% vs 63%, p < 0.01) were also higher with the rituximab-CHOP combination. Other, smaller trials with rituximab in combination with CHOP or other chemotherapeutic regimens, either as first-line therapy or for patients with relapsed or refractory aggressive B-cell NHL, have also shown promising results in terms of clinical response rates.CLL: In relatively small trials (n < 40) conducted primarily in patients with relapsed or refractory B-cell CLL, rituximab monotherapy (various regimens) achieved OR rates of 23-45%, with median duration of response ranging from approximately 3-10 months. (ABSTRACT TRUNCATED)     

Mechanism of action of rituximab

Rituximab, the humanized chimeric anti-CD20 monoclonal antibody, represents a powerful tool for treating B-cell malignancies and is licensed for the treatment of relapsed or chemorefractory low-grade or follicular non-Hodgkin's lymphoma (NHL). It has a unique mode of action and can induce killing of CD20+ cells via multiple mechanisms. The direct effects of rituximab include complement-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity, and the indirect effects include structural changes, apoptosis, and sensitization of cancer cells to chemotherapy. In vitro studies have made a significant contribution to the understanding of these mechanisms of action and have led to the development of innovative and effective treatment strategies to optimize patient response. The most significant of these strategies is the combination of rituximab and CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone), which is proving a highly effective combination in the treatment of NHL. However, all patients do not respond equally well to rituximab, and in vitro studies have identified a possible mechanism of resistance involving the anti-complement inhibitors CD55 and CD59. Neutralizing antibodies to CD55 and CD59 can overcome resistance to rituximab-mediated complement-mediated cytotoxicity in vitro. This paper overviews our understanding of the mechanisms of action of rituximab and identifies how this knowledge could be applied in a clinical setting to maximize response in both sensitive and resistant patients.