Cost utility in the United States of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone for the treatment of elderly patients with diffuse large B-cell lymphoma

BACKGROUND: Findings from the Groupe d'Etude des Lymphomes Adultes LNH 98-5 study showed that rituximab added to combined cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) prolonged progression-free survival and overall survival in adults age >/= 60 years with diffuse large B-cell non-Hodgkin lymphoma (DLBCL). The current study was conducted to investigate the incremental cost utility of the addition of rituximab to CHOP (R-CHOP) compared with CHOP alone. METHODS: Clinical prognosis of the time to disease progression and death was estimated using published evidence from the LNH 98-5 study (n = 399 patients) that was linked mathematically to published long-term outcome data on patients with DLBCL. Drug-acquisition costs were based on published data from formulary pricing sources, and the costs of cancer surveillance and end-of-life care were based on published literature sources. The authors assessed cost utility as the difference in costs between R-CHOP and CHOP divided by the increase in expected overall survival adjusted for quality of life. RESULTS: Over 5 years, it was projected that R-CHOP would prolong overall survival by 1.04 years. The mean cumulative cost of CHOP was 3358 dollars, and the mean cost of R-CHOP was 17,225 dollars, resulting in a cumulative net increase of 13,867 dollars. The posttreatment cancer surveillance cost for CHOP was 3950 dollars, compared with 5202 dollars for R-CHOP. It was estimated that R-CHOP would have a cost-utility ratio of 19,297 dollars per year of life gained compared with CHOP when adjusted for quality of life. R-CHOP remained cost effective over wide ranges of variables in sensitivity analyses. CONCLUSIONS: Compared with CHOP alone, it was predicted that R-CHOP would be cost effective in elderly patients with DLBCL.     

Maintenance therapy in lymphoma

As treatment regimens have emerged that increase the proportion of patients with lymphoma achieving responses to therapy, maintenance regimens have followed to provide means for improving progression-free survival and overall survival for responders. An ideal maintenance regimen would have limited toxicity, be easy to administer, and demonstrate a survival benefit over administration of the same agent in the relapsed disease setting. Numerous phase II and randomized trials are now maturing that examine the benefits of maintenance therapies for indolent and aggressive lymphomas. We provide a comprehensive review of existing data describing the shortcomings and benefits of interferon maintenance and rituximab maintenance therapies for patients with non-Hodgkin lymphoma (NHL). Notably, rituximab maintenance has demonstrated benefits for patients with follicular lymphoma after CVP (cyclophosphamide/vincristine/prednisone) induction therapy and after rituximab-containing chemotherapy combinations at relapse. Benefits have also been demonstrated in diffuse large B-cell lymphoma after CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) induction but not after R-CHOP (rituximab plus CHOP) induction. Randomized trials in patients with mantle cell lymphoma demonstrate a benefit for rituximab maintenance after R-FCM (fludarabine/cyclophosphamide/mitoxantrone plus rituximab) chemoimmunotherapy but not after single-agent rituximab. Further studies are needed to characterize the benefits of other agents in maintenance therapy and other strategies for maintaining remissions for patients with NHL.     

利妥昔单抗联合CHOP与单用CHOP方案治疗初治弥漫大B细胞型淋巴瘤的对比研究

目的：比较利妥昔单抗（商品名：美罗华）联合CHOP（环磷酰胺,阿霉素,长春新碱和泼尼松）与单用CHOP方案化疗治疗弥漫大B细胞淋巴瘤（diffuse large B cell lymphoma,DLBCL）的临床疗效。方法：根据患者的意愿,49例DLBCL患者分别接受6疗程CHOP方案或CHOP加利妥昔单抗方案化疗,每3周1疗程,共6个疗程。结果：R-CHOP组的CR率高于CHOP组,但差异无统计学意义（82.6%VS 65.4%,P=0.173）。中位随访时间为35月（4-66月）,R-CHOP组及CHOP组的3年OS分别为75.0%±19.6%,54.9%±20.4%,P=0.043;而3年EFS分别为69.7%±20.9%,45.8%±20.6%,P=0.029。R-CHOP组的3年OS及EFS优于CHOP组,差异有统计学意义。两组患者的不良反应无明显差别。结论：与单用CHOP方案相比,利妥昔单抗联合CHOP方案明显提高DLBCL患者的EFS及OS,而不良反应无明显增加。     

利妥昔单抗联合CHOP与单用CHOP方案治疗初治弥漫大B细胞型淋巴瘤的对比研究

目的:比较利妥昔单抗(商品名:美罗华)联合CHOP(环磷酰胺,阿霉素,长春新碱和泼尼松)与单用CHOP方案化疗治疗弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)的临床疗效。方法:根据患者的意愿,49例DLBCL患者分别接受6疗程CHOP方案或CHOP加利妥昔单抗方案化疗,每3周1疗程,共6个疗程。结果:R-CHOP组的CR率高于CHOP组,但差异无统计学意义(82.6%VS 65.4%,P=0.173)。中位随访时间为35月(4-66月),R-CHOP组及CHOP组的3年OS分别为75.0%±19.6%,54.9%±20.4%,P=0.043;而3年EFS分别为69.7%±20.9%,45.8%±20.6%,P=0.029。R-CHOP组的3年OS及EFS优于CHOP组,差异有统计学意义。两组患者的不良反应无明显差别。结论:与单用CHOP方案相比,利妥昔单抗联合CHOP方案明显提高DLBCL患者的EFS及OS,而不良反应无明显增加。     

Treatment of non-Hodgkin's lymphoma: a look over the past decade

The past decade has seen enormous changes in our understanding of lymphomas with a better classification (World Heath Organization) and identification of better prognostic factors; however, important genetic prognostic factors have not been completely analyzed. The appearance of rituximab and other monoclonal antibodies has completely revolutionized the treatment of this disease. If monoclonal antibodies have activity when used alone, most patients experienced relapse after such a treatment, even after maintenance therapy. The combination of rituximab with chemotherapy has now been shown in several randomized studies to increase the response rate, decrease the relapse rate, and prolong progression-free survival and overall survival. Rituximab plus CHOP (cyclophosphamide/doxorubicin/prednisone/vincristine; R-CHOP) has become the standard for patients with diffuse large B-cell lymphoma. Rituximab chemotherapy, probably with the CHOP regimen, is slowly gaining importance as the standard for patients with follicular lymphoma. Although little is known for other indolent lymphomas and mantle cell lymphoma, progress has been made there, too. Several questions remain for future randomized studies to continue our search toward cure.     

Rituximab Combined With MACOP-B or VACOP-B and Radiation Therapy in Primary Mediastinal Large B-Cell Lymphoma: A Retrospective Study

BackgroundThird-generation regimens (MACOP-B [methotrexate/leucovorin (LV)/doxorubicin/cyclophosphamide/vincristine/prednisone/bleomycin] or VACOP-B [etoposide/LV/doxorubicin/cyclophosphamide/vincristine/prednisone/bleomycin]) in combination with local radiation therapy seem to improve lymphoma-free survival of primary mediastinal large B-cell lymphoma (PMLBCL). Recently, the superiority of R-CHOP (rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone) over CHOP-like regimens has been demonstrated in elderly and younger patients with low-risk diffuse large B-cell lymphoma.Patients and MethodsRetrospectively, between February 2002 and July 2006, 45 previously untreated patients with PMLBCL were treated with a combination of a third-generation chemotherapy regimen (MACOP-B or VACOP-B), concurrent rituximab, and mediastinal radiation therapy.ResultsTwenty-six (62%) patients achieved a complete response (CR), and 15 (36%) obtained a partial response after MACOP-B/VACOP-B plus rituximab. After radiation therapy, the CR rate was 80%. At a median follow-up of 28 months, among the 34 patients who obtained a CR, 3 relapsed after 16, 19, and 22 months, respectively. Projected overall survival was 80% at 5 years; the relapse-free survival (RFS) curve of the 34 patients who achieved CR was 88% at 5 years.ConclusionIn this retrospective study, in patients with PMLBCL, combined-modality treatment using the MACOP-B/VACOP-B regimen plus rituximab induces a high remission rate, with patients having a > 80% chance of surviving relapse free at 5 years. In comparison with historical data on MACOP-B/VACOP-B without rituximab, there are no statistically significant differences in terms of CR and RFS rates.     

Bcl-2 gene expression as a predictor of outcome in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with a 5-year survival rate of 35%-60%. Various clinical factors included in the International Prognostic Index have failed to identify the patients with DLBCL who will not benefit from the standard R-CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone plus rituximab) treatment regimen. Bcl-2 has been implicated in conferring resistance to chemotherapy in non-Hodgkin's lymphoma and is therefore a candidate prognostic marker in DLBCL. To identify the correlation between Bcl-2 expression and response to rituximab-containing treatment regimens, histologic materials were analyzed from 292 elderly patients with confirmed DLBCL. Of these, 155 patients had received R-CHOP (53%) and 137 had received CHOP (47%). One hundred ninety-three patients (66%) were found to express high levels of Bcl-2 protein in > 50% of the tumor cells. Of the 193 Bcl-2-positive patients, the patients who received R-CHOP had a better 5-year overall rate than patients treated with CHOP (56% vs. 42%; P = 0.01), whereas in the patients with Bcl-2-negative disease, there was no statistically significant difference in the 5-year overall survival rates between the R-CHOP and CHOP regimens (58% vs. 52%; P = 0.6). Therefore, the addition of rituximab to the standard chemotherapy regimen seems to have overcome the Bcl-2-associated resistance to chemotherapy.     

Strategies for improving outcomes with 14-day anthracycline-based regimens in patients with aggressive lymphomas

Among the strategies developed to improve results in patients with diffuse large B-cell lymphoma, increasing the dose of CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) regimen (dose-intense regimen) and decreasing the duration of cycles (dose-dense regimen) or doing both had been proposed before the rituximab era. With granulocyte colony-stimulating factor support, both regimens are feasible without severe hematologic toxicities. Randomized studies have shown better results than with standard CHOP with longer survivals. However, the addition of rituximab to CHOP (R-CHOP) has also dramatically improved the results without increasing the toxicity. Whether the addition of density or intensity to R-CHOP will continue to improve the results are not known, and preliminary results might challenge this hypothesis. The future benefit for patients with adverse prognostic parameters might not come from dose-dense or dose-intense CHOP-like regimens but from the addition of another drug to R-CHOP.     

Treatment of diffuse large B-cell lymphoma in the elderly: Strategies integrating oncogeriatric themes

With an increasingly aged population, many patients will present with diffuse large B-cell lymphoma in their 70s and 80s. Recently, several randomized studies have confirmed the benefit of rituximab in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and showed a substantial improvement in the outcome of fit elderly patients. This article reviews the efficacy and toxicity of the current treatment regimens applied for the treatment of diffuse large B-cell lymphoma in elderly patients and provides practical recommendations for the management of these patients.     

Bcl-2 Gene Expression as a Predictor of Outcome in Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with a 5-year survival rate of 35%–60%. Various clinical factors included in the International Prognostic Index have failed to identify the patients with DLBCL who will not benefit from the standard R-CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone plus rituximab) treatment regimen. Bcl-2 has been implicated in conferring resistance to chemotherapy in non-Hodgkin's lymphoma and is therefore a candidate prognostic marker in DLBCL. To identify the correlation between Bcl-2 expression and response to rituximabcontaining treatment regimens, histologic materials were analyzed from 292 elderly patients with confirmed DLBCL. Of these, 155 patients had received R-CHOP (53%) and 137 had received CHOP (47%). One hundred ninety-three patients (66%) were found to express high levels of Bcl-2 protein in > 50% of the tumor cells. Of the 193 Bcl-2-positive patients, the patients who received R-CHOP had a better 5-year overall rate than patients treated with CHOP (56% vs. 42%; P = 0.01), whereas in the patients with Bcl-2-negative disease, there was no statistically significant difference in the 5-year overall survival rates between the R-CHOP and CHOP regimens (58% vs. 52%; P = 0.6). Therefore, the addition of rituximab to the standard chemotherapy regimen seems to have overcome the Bcl-2-associated resistance to chemotherapy.     

Protein Kinase C Beta II Expression in Diffuse Large B-Cell Lymphoma Predicts for Inferior Outcome of Anthracycline-Based Chemotherapy With And Without Rituximab

Protein kinase C beta II expression in diffuse large B-cell lymphoma has prognostic significance not only for CHOP therapy in low-risk International Prognostic Index disease but also for all patients receiving CHOP plus rituximab.Full AbstractIntroductionProtein kinase C beta II (PKCbII) expression has been reported to indicate inferior prognosis in diffuse large B-cell lymphoma (DLBCL) treated with anthracycline-based chemotherapy.AimTo compare the prognostic significance of immunohistochemically determined PKCbII expression in de novo DLBCL treated with CHOP chemotherapy (cyclophosphamide/doxorubicin/vincristine/prednisone) with and without rituximab.Patients and Methods80 consecutive patients treated at St. Vincent's Hospital with de novo DLBCL, 48 treated with CHOP, and 32 with R-CHOP (rituximab plus CHOP), were studied using immunohistochemistry for PKCbII on diagnostic tissue samples. Staining results were correlated with patient characteristics and clinical outcome. Overall survival (OS) and progression-free survival (PFS) were determined by the Kaplan-Meier method, and comparisons were determined by the log-rank test.ResultsPKCbII expression correlated with inferior OS and PFS in CHOP-treated patients with low-risk International Prognostic Index (IPI) disease (0–2 adverse factors) but not in the overall patient group unstratified by IPI. PKCbII expression significantly correlated with inferior OS and PFS in R-CHOP—treated patients unstratified by IPI status.ConclusionPKCbII expression has prognostic significance not only for CHOP therapy in low-risk IPI disease but also for all patients receiving R-CHOP. Immunohistochemically demonstrated PKCbII expression thus identified patient subgroups in which alternative treatment strategies might confer superior outcome.     

利妥昔单抗联合CHOP方案治疗骨原发性非何杰金淋巴瘤的疗效和预后分析

目的骨的原发性淋巴瘤虽然可以通过化疗和放疗得到有效控制,但复发的比率很高。本研究旨在分析和评价利妥昔单抗联合CHOP方案治疗CD20阳性骨原发性非何杰金淋巴瘤的临床疗效及其安全性。方法回顾11例利妥昔单抗联合CHOP方案治疗的骨原发性非何杰金淋巴瘤患者临床资料,利妥昔单抗用药方法为375mg／m^2,于每周期化疗前1d静脉滴注,每3周为1个循环周期;6～8个周期后评价疗效及不良反应,同时与单纯应用CHOP化疗的患者进行回顾性疗效分析比较。结果11例患者接受利妥昔单抗联合CHOP方案化疗,完全缓解（CR）8例,部分缓解（PR）3例。随诊时间9—65个月,8例无瘤生存,1例转化为淋巴细胞型白血病,患者带瘤生存,2例死亡,患者生存率81．8％（9／11）,无病生存率72．7％（8／11）;Kaplan—Meier生存曲线计算应用利妥昔单抗的患者5年预期整体生存率（overall survival,OS）为60．6％。R—CHOP化疗后最常见的复发部位为中枢神经系统。不良反应与单纯应用CHOP化疗组无显著差异,主要为过敏和发热,以及化疗相关的血液学毒性,未出现爆发性肝衰竭。结论利妥昔单抗联合CHOP方案治疗骨原发性非何杰金淋巴瘤（CD20^＋）效果显著,如何降低中枢神经系统复发是今后的研究方向。     

放疗对早期弥漫大B细胞淋巴瘤化疗后CR患者的价值研究

目的 探讨放疗在早期弥漫大B细胞淋巴瘤(DLBCL)化疗后达CR患者中的地位。方法 回顾分析2004—2012年本院治疗的376例Ⅰ、Ⅱ期DLBCL患者资料,均接受至少3个周期CHOP和利妥昔单抗+CHOP方案化疗(R-CHOP)后达CR者。R-CHOP组92例,R-CHOP+放疗组79例,CHOP+放疗组98例,CHOP组107例。放疗为累及野照射30~56 Gy。Kaplan-Meier法计算生存率并Logrank法检验,Cox回归模型多因素预后分析。结果 5年样本量为188例。全组5年DFS、OS分别为80.7%、87.6%,R-CHOP+放疗组和R-CHOP组的分别为94.9%和88.1%(P=0.030)、97.9%和86.0%(P=0.026),CHOP+放疗组和CHOP组的分别为74.2%和71.4%(P=0.623)、87.0%和82.1%(P=0.420)。多因素分析显示吸烟指数<500、IPI<2、加用利妥昔单抗是预后有利因素(P=0.034~0.000)。结论 放疗对早期DLBCL可以提高R-CHOP化疗后CR者的DFS和OS。建议DLBCL使用含利妥昔单抗的化疗,R-CHOP化疗后应接受放疗。希望开展随机对照研究进一步证明该结果。     

侵袭性B细胞淋巴瘤新的标准治疗方案

实施CHOP方案(环磷酰胺、阿霉素、长春新碱和泼尼松)治疗20多年来,侵袭性B细胞淋巴瘤已成为可治愈的疾病,CHOP方案也已成为治疗这一疾病的标准方案。但其治愈率只有35%~40%,半数以上复发。随着抗B细胞表面抗原CD20的人鼠嵌合型单克隆抗体利妥昔(rituximab)的应用,侵袭性B细胞淋巴瘤的治疗已发生了根本改变。多项大型Ⅲ期随机临床研究结果证实,利妥昔与CHOP方案或CHOP样方案联合应用,比单纯联合化疗能明显改善侵袭性B细胞淋巴瘤的有效率,无事件生存和长期生存结果,无论是老年或年轻患者,低危预后还是高危预后患者,均有显著的统计学差异。因此,利妥昔加CHOP或CHOP样方案的联合治疗已成为侵袭性B细胞淋巴瘤新的标准治疗方案。     

Rituximab for HIV-associated lymphoma: weighing the benefits and risks

PURPOSE OF REVIEW: This review discusses the potential benefits and risks of using the anti-CD20 monoclonal antibody rituximab for the treatment of HIV-associated B-cell non-Hodgkin's lymphoma. RECENT FINDINGS: Studies have consistently demonstrated that rituximab improves response and survival when combined with standard chemotherapy compared with chemotherapy alone in immunocompetent patients with intermediate-grade non-Hodgkin's lymphoma. Several recently reported phase II and III trials have evaluated the use of rituximab plus chemotherapy for HIV-associated B-cell non-Hodgkin's lymphoma. Phase II trials combining rituximab with either standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy or infusional chemotherapy have reported encouraging results, suggesting a similar benefit in HIV-positive individuals. A phase III trial comparing CHOP with CHOP-plus rituximab (R-CHOP) demonstrated a lower risk from progression of the lymphoma, but a higher risk of early and late infectious-related death in patients with a low CD4 count (< 50/microL). SUMMARY: Rituximab should be used cautiously in patients with advanced HIV infection who have a CD4 count of less than 50/microL, as it seems to increase the risk of developing fatal infectious complications. In patients with higher CD4 counts, the benefit of rituximab may outweigh its risk, although this has yet to be confirmed in prospective, randomized trials specifically performed in this population.     

R-CHOP versus R-COMP: Are They Really Equally Effective?

The first-line standard treatment for diffuse large B-cell lymphoma (DLBCL) is the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). It is associated with cardiotoxicity, which is why new treatment strategies are needed. Liposomial doxorubicin has been proven to reduce these side-effects, but until now a direct comparison regarding efficacy has not yet been published. We retrospectively assessed 364 consecutive DLBCL patients who underwent either R-CHOP (218; 60%) or R-COMP (doxorubicin replaced by non-pegylated liposomal doxorubicin; 146; 40%) in first line and compared outcome and survival. We provide evidence that both regimens induce a high and comparable number of complete remissions and that both are able to cure patients with DLBCL. Confirmatory data are needed.     

Dose-escalated CHOEP for the treatment of young patients with aggressive non-Hodgkin's lymphoma: II. Results of the randomized high-CHOEP trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL).

BACKGROUND: The addition of etoposide to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone [etoposide to combination chemotherapy with cyclophosphamide, vincristine and prednisone (CHOEP)] improved outcome of young patients with good-prognosis aggressive lymphoma. To improve results further, the maximal dose-escalated version of CHOEP-21 tolerable without stem-cell support (high CHOEP: cyclophosphamide 1400 mg/m2, doxorubicin 65 mg/m2, vincristine 2 mg, etoposide 175 mg/m2 x3, prednisone 100 mg x5) was compared with CHOEP-21. PATIENTS AND METHODS: Intention-to-treat analysis of 389 young (18-60 years) patients with good-prognosis (age-adjusted International Prognostic Index = 0, 1) aggressive lymphoma randomized to CHOEP-21 (n = 194) or high CHOEP (n = 195). RESULTS: There was no difference in 3-year event-free (64% versus 67%; P = 0.734) or overall survival (83% versus 87%; P = 0.849). Neither low-risk nor low-intermediate risk patients benefited from high CHOEP. High CHOEP was more toxic than CHOEP-21 (grades 3 and 4 leukocytopenia 100% versus 87.2%, P < 0.001; thrombocytopenia 80.8% versus 9.6%, P < 0.001; infections 35% versus 11%, P < 0.001; therapy-associated deaths 3.1% versus 0%, P = 0.03). CONCLUSION: Dose-escalated CHOEP-21 does not provide clinical benefit for young patients with good-prognosis aggressive lymphomas. Since differences between chemotherapy regimens are compressed by the addition of rituximab, the results of this trial have bearing on strategies aiming to improve outcome of good-prognosis aggressive lymphomas in the rituximab era.     

Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era

We evaluated the usefulness of prognostic markers in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) ± rituximab (R-CHOP) in Japan. We studied 730 patients with DLBCL; 451 received CHOP and 279 R-CHOP. We analyzed biopsy samples immunohistochemically for markers of germinal center B cells (CD10, Bcl-6), postgerminal center B cells (Multiple myeloma-1), and apoptosis (Bcl-2). The median follow-up period for surviving patients was 56.4 months for the CHOP group and 25.2 months for the R-CHOP group. DLBCL were categorized as germinal center B (GCB) subtype (352/730; 48.2%) or non-GCB subtype (378/730; 51.8%). In the CHOP group, the high expression of CD10 ( P  = 0.022) or Bcl-6 ( P  = 0.021), or GCB subtype ( P  = 0.05) was associated with better overall survival, whereas the high expression of Bcl-2 ( P  = 0.001) or MUM1 ( P  = 0.011), or non-GCB subtype ( P  = 0.05) was associated with worse overall survival. In the R-CHOP group, however, these biomarkers except Bcl-6 were not significant prognostic factors. The patients with non-GCB subtype showed improved survival in the R-CHOP group ( P  = 0.756). The International Prognostic Index was a useful clinical marker of survival in the CHOP group ( P  < 0.001) and also in the R-CHOP group ( P  < 0.001). Results of improved survival with rituximab addition indicate that the relevance of previously recognized prognostic factors should be re-evaluated. ( Cancer Sci  2009; 100: 1842–1847)     

The role of mitoxantrone in non-Hodgkin's lymphoma

The development of doxorubicin was an important advance in the treatment of patients with non-Hodgkin's lymphoma (NHL). Alternatives to doxorubicin, such as mitoxantrone (Novantrone), have less nonhematologic toxicity and could offer a therapeutic advantage in some situations if similar antilymphoma activity exists. Several combination regimens that include mitoxantrone have been shown to be active. These include mitoxantrone/ifosfamide (Ifex) and mitoxantrone/etoposide combinations as salvage therapy for aggressive lymphomas. Mitoxantrone in combination with fludarabine (Fludara) for the treatment of newly diagnosed follicular lymphomas and in combination with fludarabine and dexamethasone for relapsed/refractory follicular lymphomas has produced high complete response rates. Other evolving uses of mitoxantrone include combination therapy with cladribine (Leustatin) or rituximab (Rituxan), and as part of conditioning regimens for hematopoietic stem cell transplantation. In diffuse aggressive lymphoma, mitoxantrone, 10 mg/m2, substituted for doxorubicin, 50 mg/m2, results in a poorer response when CNOP (cyclophosphamide [Cytoxan, Neosar], mitoxantrone [Novantrone], vincristine [Oncovin], prednisone) is compared to CHOP (cyclophosphamide, doxorubicin HCl vincristine, prednsione); however, increasing the mitoxantrone dose to 12 mg/m2 in either the CNOP or CMP-BOP (cyclophosphamide, mitoxantrone, procarbazine [Matulane], bleomycin [Blenoxane], vincristine, prednisone) regimens yields results comparable to those achieved with the doxorubicin-containing regimen. Comparable results have also been observed when 10 mg/M2 of mitoxantrone was substituted for 45 mg/M2 of doxorubicin in the m-BACOD (methorexate, bleomycin, doxorubicin [Adriamycin], cyclophosphamide, vincristine, dexamethasone) regimen. Mitoxantrone is active in NHL, and combinations including mitoxantrone can be used effectively and may provide an advantage in the elderly.     

Evolving role of rituximab in the treatment of patients with non-Hodgkin's lymphoma

Rituximab is the first monoclonal antibody to have been registered for the treatment of B-cell lymphomas. Randomized studies have demonstrated its activity in follicular lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma in untreated or relapsing patients. Rituximab has transformed the outcome of these patients because of its high activity and low toxicity. A combination of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, has the highest efficacy ever described with any chemotherapy in diffuse large B-cell lymphoma and follicular lymphoma.