Lazzarino Mario, Arcaini Luca, Orlandi Ester, Iacona Isabella, Bernasconi Paolo, Calatroni Silvia, Varettoni Marzia, Isa Luciano, Brusamolino Ercole, Bonfichi Maurizio, Passamonti Francesco, Burcheri Sara, Pascutto Cristiana, Regazzi Mario
Division of Hematology, IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.
Oncology. 2005;68(2-3):146-53. doi: 10.1159/000086769. Epub 2005 Jul 4.
Therapeutic options for relapsed or refractory follicular lymphoma include combination chemotherapy, immunotherapy and, for selected patients, autotransplant. Because of the different mechanisms of action and non-overlapping toxicities, combination of rituximab with chemotherapy is a rational approach.
30 patients with follicular non-Hodgkin's lymphoma with advanced-stage disease were treated with four cycles of immunochemotherapy with rituximab 375 mg/m2 on day 1, vincristine 2 mg i.v. on day 2 and cyclophosphamide 400 mg/m2 i.v. from days 2 to 6, repeated at 3-week intervals. All patients had received multiple lines of therapy (median 3); 9 (30%) had relapses (2 after high-dose therapy with autologous transplant), and 21 (70%) were in relapse and refractory to salvage treatment (with an anthracycline-containing regimen in 19).
Of 29 patients evaluable for response, 16 (55 %) obtained a complete response (CR) and 3 (10%) a partial response (PR), with an overall response rate of 65% (19/29); 10 patients (35%) achieved less than PR. The median event-free survival was 16.1 months for all patients, being 22.8 months for responders. After a median follow-up of 2 years from the start of therapy (range 6 months to 3.8 years), of 16 patients who achieved CR, 10 remain free of disease.
The combination of rituximab with vincristine and 5-day cyclophosphamide is able to produce CR in patients with advanced follicular lymphoma, even in patients resistant to third-generation regimens. The regimen designed on the basis of pharmacokinetics of the chimeric antibody seemed important for the clinical efficacy of the combination.
复发或难治性滤泡性淋巴瘤的治疗选择包括联合化疗、免疫疗法,对于部分患者还包括自体移植。由于作用机制不同且毒性不重叠,利妥昔单抗与化疗联合是一种合理的方法。
30例晚期滤泡性非霍奇金淋巴瘤患者接受了4个周期的免疫化疗,第1天给予利妥昔单抗375 mg/m²,第2天静脉注射长春新碱2 mg,第2至6天静脉注射环磷酰胺400 mg/m²,每3周重复一次。所有患者均接受过多种治疗方案(中位次数为3次);9例(30%)出现复发(2例在自体移植大剂量治疗后复发),21例(70%)处于复发状态且对挽救治疗耐药(19例采用含蒽环类药物的方案)。
在29例可评估疗效的患者中,16例(55%)获得完全缓解(CR),3例(10%)获得部分缓解(PR),总缓解率为65%(19/29);10例患者(35%)缓解程度低于PR。所有患者的无事件生存期中位数为16.1个月,缓解者为22.8个月。从治疗开始中位随访2年(范围6个月至3.8年),16例获得CR的患者中,10例仍无疾病复发。
利妥昔单抗与长春新碱及5天环磷酰胺联合能够使晚期滤泡性淋巴瘤患者产生CR,即使是对第三代方案耐药的患者。基于嵌合抗体药代动力学设计的方案似乎对联合治疗的临床疗效很重要。