Randomized phase III study of fludarabine phosphate versus cyclophosphamide, vincristine, and prednisone in patients with recurrent low-grade non-Hodgkin's lymphoma previously treated with an alkylating agent or alkylator-containing regimen.

PURPOSE: To compare in a phase III study the safety and efficacy of fludarabine to that of cyclophosphamide, vincristine, and prednisone (CVP) in recurrent, low-grade, non-Hodgkin's lymphoma after previous response to systemic treatment. PATIENTS AND METHODS: Patients were randomized to fludarabine (25 mg/m(2) intravenously on days 1 to 5, every 28 days) or CVP (cyclophosphamide 750 mg/m(2) and vincristine 1.2 mg/m(2) both intravenously on day 1 and prednisone 40 mg/m(2) orally on days 1 to 5, every 21 days). The primary outcome assessed was progression-free survival (PFS); secondary outcomes included treatment-free survival (TFS), overall survival (OS), treatment-related toxicity, and quality of life (QoL) according to the European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire C-30 version 1.0 instrument. RESULTS: Ninety-one patients were randomized, 47 to fludarabine and 44 to CVP. There was no difference in response rates, with 64% (complete response [CR], 9%) for fludarabine versus 52% (CR, 7%) for CVP (P =.72). With a median follow-up of 42 months, median PFS (11 months v 9.1 months; P =.03) and TFS (15 months v 11 months; P =.02) were superior in patients receiving fludarabine. No difference in median overall survival was detected (57 months for fludarabine v 44 months for CVP; P =.95). Three patients receiving fludarabine died of treatment-related toxicity compared with none of the patients receiving CVP. Peripheral neuropathy and alopecia were more common with CVP. Patients receiving fludarabine had higher scores for social function (P =.008); no other differences in QoL were detected. CONCLUSION: In recurrent low-grade lymphoma, fludarabine improves PFS, TFS, and social function scores in comparison with CVP but does not improve OS.     

VNCOP-B (etoposide, mitoxantrone, cyclophosphamide, vincristine, predonisolone, bleomycin) therapy in elderly patients with aggressive non-Hodgkin lymphoma--a study of efficacy and safety, final report

We experienced the VNCOP-B (etoposide, mitoxantrone, cyclophosphamide, vincristine, predonisolone, bleomycin) combination regimen for the treatment of elderly patients with aggressive non-Hodgkin lymphoma (NHL) in a multicenter study by 6 collaborative institutions. Patients were previously untreated > or = 60 years of age and received prophylactic G-CSF. Twenty patients entered this trial, and all of them were evaluated for feasibility, toxicity, and efficacy. The complete remission rate was 75.0%, with a 100% overall response rate; overall survival (OS) rate at 3 years was 79.1% (median follow up 761.5 days), with a 60.7% progression-free 3-year survival (PFS) rate (median follow-up 600.0 days). Our trial was promising and well-tolerated. According to IPI, high/high-intermediate risk was associated with significantly worse OS and PFS than low/low-intermediate risk (2-year OS: 51.8% versus 100.0%, p=0.0118; 2-year PFS: 33.3% versus 80.0%, p=0.0125). Grade 3/4 infections occurred in 3 patients, but no patients experienced it with predonisolone reduced.     

The role of mitoxantrone in the treatment of indolent lymphomas

With the introduction of newer therapeutic approaches, survival in indolent non-Hodgkin's lymphoma (NHL) appears to be improving. Mitoxantrone (Novantrone; Serono, Inc.; Rockland, MA, http://www.seronousa.com), an anthracenedione with low cardiotoxic potential, has demonstrated activity in indolent NHL in combination with fludarabine (Fludara; Berlex Laboratories; Wayne, NJ, http://www.berlex.com) and other agents. In a Southwest Oncology Group trial (SWOG 9501), treatment with fludarabine and mitoxantrone (FM) induced a complete remission (CR) rate of 44% and a partial remission (PR) rate of 50% in untreated patients. The estimated 4-year progression-free survival (PFS) rate was 38%. In a multicenter Italian trial comparing the efficacy of FM with that of cyclophosphamide, doxorubicin (Adriamycin; Bedford Laboratories; Bedford, OH, http://www.bedfordlabs.com), vincristine (Oncovin; Eli Lilly and Company; Indianapolis, IN, http://www.lilly.com), and prednisone (Deltasone; Pfizer Pharmaceuticals; New York, NY, http://www.pfizer.com), CHOP, followed by rituximab (Rituxan; Genentech, Inc.; South San Francisco, CA, http://www.gene.com) for patients with incomplete clinical or molecular responses, the CR and molecular response rates were significantly higher in the FM arm, but the PFS and overall survival (OS) rates did not differ between the two arms. However, FM was also significantly less toxic than CHOP. The administration of rituximab following chemotherapy resulted in higher clinical and molecular response rates in both arms. In a separate trial, FM plus dexamethasone (Decadron; Merck and Co., Inc.; Whitehouse Station, NJ, http://www.merck.com), FND, plus concurrent rituximab produced a CR rate of 92%. In a randomized German study, patients with indolent lymphomas received FM plus cyclophosphamide (FCM) or FCM with rituximab. PFS and OS times were significantly better for patients who received combined chemoimmunotherapy. Mitoxantrone-based regimens are highly active and well tolerated in patients with both relapsed and previously untreated indolent lymphomas. The addition of rituximab appears to increase the activity of the FM, FND, and FCM regimens. Although the results of the Italian multicenter study support the superiority of FM over CHOP in terms of clinical and molecular responses and tolerability, additional studies using rituximab in combination with both of these regimens should be attempted to determine the possible further benefit of both in the management of indolent lymphoma. Because cure remains elusive in patients with indolent lymphoma, maximum prolongation of PFS with minimal toxicity and maximum preservation of quality of life should remain central goals of treatment.     

Fludarabine, cyclophosphamide and mitoxantrone in relapsed or refractory chronic lymphocytic leukemia and low grade non-Hodgkin's lymphoma

A regimen combining fludarabine, cyclophosphamide and mitoxantrone (FCM) was used to treat 29 patients with relapsed or refractory chronic lymphocytic leukemia (CLL, N = 24) and low-grade non-Hodgkin's lymphoma (NHL, N = 5) based on evidence suggesting synergism between the 3 drugs. Patients were treated with mitoxantrone 5mg/m2 i.v. day 1 only, fludarabine 25 mg/m2 i.v. for 3 days or 24 mg/m2 orally for 5 days, cyclophosphamide 250 mg/m2 i.v. for 3 days or 150 mg/m2 orally for 5 days inclusive. Eighteen patients had previously received fludarabine and most were heavily pretreated with 40% having >2 prior treatments. A median number of 4 FCM courses (range of 1-9) were given. The response rate was 78.5%: 32% complete remission, 25% nodular partial remission, 21.5%, partial remission. Median duration of response was 19 months and median survival was 42 months. Sixteen patients (57%) developed neutropenia to < 0.5 x 10(9)/l and 12 (43%) infectious complications. Four patients developed large cell lymphoma (Richter's syndrome) and 2 acute myeloid leukemia. FCM is a useful combination for relapsed or refractory CLL and low grade NHL with high response rates and long duration of response. The role of FCM as first line therapy deserves study as well as its combination with the monoclonal antibody Rituximab.     

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.     

Randomized comparison of cladribine alone or in combination with cyclophosphamide, and cyclophosphamide, vincristine and prednisone in previously untreated low-grade B-cell non-Hodgkin lymphoma patients: final report of the Polish Lymphoma Research Group

BACKGROUND: The objective of this study was to compare the efficacy of 3 regimens, cladribine alone, cladribine and cyclophosphamide combination, or cyclophosphamide, vincristine, and prednisone combination in previously untreated patients with low-grade B-cell non-Hodgkin lymphoma (LGNHL). METHODS: For this 3-arm, phase 3 study, 197 patients were randomly allocated to receive 6 monthly courses of cladribine alone, cladribine and cyclophosphamide combination, or cyclophosphamide, vincristine, and prednisone combination. Patients for whom all clinical data were available and 162 patients who completed scheduled chemotherapy were analyzed for the endpoints of this study. RESULTS: Compared with cyclophosphamide, vincristine, and prednisone combination regimen, cladribine alone or cladribine and cyclophosphamide combination induced higher probability of overall response (odds ratio [OR] = 4.0; 95% confidence interval [CI], 1.7-9,3; P = .002, and OR = 8.5; 95% CI, 3.2-22.7; P < .0001, respectively), complete remission (OR = 5.8; 95% CI, 1.8-18.5; P = .003; and OR = 14; 95% CI, 4.4-44; P < .0001, respectively), progression-free survival (log-rank test P < .0001), but not overall survival. After incorporating the International Prognostic Index in multivariate analysis, treatment with cladribine-containing regimens remained an independent prognostic factor for progression-free survival (chi(2) = 35.94; hazard ratio = 2.38; P < .0002). Incidences of infections were similar in the randomized groups, whereas cladribine and cyclophosphamide combination, but not cladribine alone, induced more frequent neutropenia, anemia, and thrombocytopenia compared with cyclophosphamide, vincristine, and prednisone combination (P < .05 for each). This resulted in a higher frequency of prolongation of intervals between cladribine and cyclophosphamide combination and cyclophosphamide, vincristine, and prednisone combination cycles (P < .05), but dose reductions due to hematological or other toxicity did not differ significantly in cladribine alone, cladribine and cyclophosphamide combination, and cyclophosphamide, vincristine, and prednisone combination groups. CONCLUSIONS: For patients with LGNHL, first-line cladribine alone or cladribine and cyclophosphamide combination regimens both provided similar treatment responses, acceptable toxicity, and better response rates than cyclophosphamide, vincristine, and prednisone combination.     

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.     

FND与CHOP方案治疗进展期惰性淋巴瘤的疗效比较

目的比较FND(氟达拉滨 米托蒽醌 地塞米松)与CHOP方案治疗进展期惰性淋巴瘤的疗效与安全性。方法临床观察的终点包括缓解率(总有效率OR和完全缓解率CR),无失败生存(FFS),总体生存(OS)及毒性。40例病人随机分组,FND和CHOP组各20例。两种治疗方案均为每28天1次,共3个疗程,之后,二组病人均采用CHOP方案巩固3个疗程。FND方案为氟达拉滨25mg/m2,ivd1~5;米托蒽醌10mg/m2,ivd1;地塞米松20mg/d,ivd1~5。CHOP方案为环磷酰胺600mg/m2,ivd1;阿霉素25mg/m2,ivd1;长春新碱1.4mg/m2,ivd1和强的松50mg/m2,pod1~5。结果FND方案的完全缓解率和总有效率显著优于CHOP(OR83%vs40%,CR50%vs15%;P<0.01)。FND组的中位FFS是32个月,而CHOP组仅为15个月。两种治疗方案的耐受性均较好,只有少量的感染并发症发生。结论FND方案的完全缓解率、总有效率均显著优于CHOP,并可有效改善预后。     

Brief-Duration Rituximab/Chemotherapy Followed by Maintenance Rituximab in Patients With Diffuse Large B-Cell Lymphoma Who Are Poor Candidates for R-CHOP Chemotherapy: A Phase II Trial of the Sarah Cannon Oncology Research Consortium

Introduction:Patients with diffuse large B-cell lymphoma (DLBCL) who are very elderly or have poor performance status are difficult to treat with a full course of R-CHOP (rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone) therapy. In this phase II trial, we treated this group of patients with a novel regimen containing 3 courses of rituximab/chemotherapy followed by maintenance rituximab.Patients and Methods:Patients with newly diagnosed stage II-IV DLBCL were eligible if they were considered poor candidates for 6-8 cycles of R-CHOP therapy. Patients who were eligible for anthracycline therapy received 3 cycles of rituximab plus cyclophosphamide/mitoxantrone/vincristine/prednisone (CNOP); the remainder of patients received R-CVP (rituximab plus cyclophosphamide/vincristine/prednisone). Patients without progression after completion of 3 cycles received 4 courses of maintenance rituximab (375 mg/m² weekly × 4, repeated every 6 months) for 24 months.Results:Between May 2003 and July 2007, 51 patients were enrolled. The median age was 78 years, and 43% of patients were > 80 years of age. Nineteen patients (37%) had Eastern Cooperative Oncology Group performance status of 2, and 72% had high-intermediate or high-risk International Prognostic Index scores. After a median follow-up of 48 months, the 2-, 3-, and 4-year progression-free survival rates are 71%, 65%, and 56%, respectively. The 2-, 3-, and 4-year overall survival rates are 72%, 67%, and 67%, respectively. Treatment was well tolerated, with few severe toxicities and no treatment-related deaths.Conclusion:This abbreviated course of rituximab/chemotherapy, followed by maintenance rituximab, was active and well tolerated in these very elderly patients. Brief-duration rituximab/chemotherapy as well as maintenance rituximab merit further evaluation in this setting.     

Phase II study of chemotherapy and stem cell transplantation for adult acute lymphoblastic leukemia or lymphoblastic lymphoma: Japan Clinical Oncology Group Study 9004

Granulocyte colony-stimulating factor (G-CSF)-supported, post-remission chemotherapy (Cx) for adult acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) was evaluated. One hundred and forty-three eligible patients (median age, 41 years) including 126 ALL and 17 LBL receiving induction Cx (vincristine, cyclophosphamide, prednisolone [PSL], doxorubicin, L-asparaginase, intrathecal-methotrexate [IT-MTX]) were analyzed. For patients achieving complete response (CR), two courses of post-remission Cx (course A of daunorubicin, cytosine arabinoside, vindesine, PSL plus IT-MTX; course B of mitoxantrone, etoposide, vincristine, PSL plus IT-MTX) with the use of G-CSF were repeated alternately; thereafter, maintenance Cx including MTX and 6-mercaptopurine was given for 2 years. One hundred and nineteen (83%) patients achieved CR, while 14 (10%) died during induction. Among the 119 patients achieving CR, five died in remission, 76 relapsed, and the remaining 38 were alive without disease. The median survival time of the 143 eligible patients was 26 months (95% confidence interval, 19-34). At a median follow-up time of 9 years, the 5-year survival rate was 32% and the 5-year progression-free survival (PFS) rate was 26%. The 5-year survival rate of 36 patients who underwent autologous (n = 20) or allogeneic stem cell transplantation (SCT; n = 16) in the first CR group was 58%. Compared with the authors' previous trials, survival and PFS were markedly improved. In conclusion, G-CSF-supported, intensive post-remission Cx and subsequent SCT are worthy of further investigation for the treatment of adult ALL and LBL.     

Primary treatment of low-grade non-Hodgkin's lymphoma with the combination of fludarabine and mitoxantrone: a phase II study of the Hellenic Cooperative Oncology Group

The treatment of patients with recurrent low-grade lymphoma with the combination of fludarabine, mitoxantrone and dexamethasone has been associated with significant activity but has also caused frequent infectious complications. We designed a phase II study for previously untreated patients with the combination of fludarabine and mitoxantrone but without steroids. Our aim was to assess the activity of this combination as primary treatment for low-grade lymphoma and to avoid the additional immunosuppression induced by dexamethasone. Twenty seven patients with low-grade lymphoma received fludarabine 25 mg/m2/day i.v. on days 1-3 and mitoxantrone 10 mg/m2 i.v. on day 1. The treatment was repeated every 28 days for a maximum of six cycles. Twenty patients (74%) achieved an objective response including 12 (44%) complete and 8 (30%) partial responses. The main toxicity was grade III or IV neutropenia, which occurred in 40% of patients but there were no severe opportunistic infections. The median time to progression for all patients was 32 months. With a median follow-up of 33.4 months, six patients have died and the probability of survival at 3 years is 75%. We conclude that the fludarabine and mitoxantrone regimen is safe and effective for newly diagnosed patients with low-grade lymphoma who require treatment. Prospective randomized trials are needed in order to assess the impact of this treatment on patients' survival.     

氟达拉滨为主的联合化疗方案治疗低度恶性非霍奇金淋巴瘤的临床观察

目的评价以氟达拉滨为主的化疗方案治疗低度恶性淋巴瘤的疗效和不良反应。方法采用氟达拉滨为主的化疗方案(FMD方案:氟达拉滨 米托蒽醌 地塞米松;FMC方案:氟达拉滨 米托蒽醌 环磷酰胺;FC方案:氟达拉滨 环磷酰胺)治疗我院收治的低度恶性非霍奇金淋巴瘤患者32例,其中初发19例,复发、难治13例。结果32例患者平均完成了4.1个疗程,完全缓解(CR)率为65.6%,部分缓解(PR)率为18.8%,总的有效(OR)率为84.4%。初发组CR率71.4%, PR率21.0%,OR率92.4%;复发、难治组CR率46.2%,PR率13.1%,OR率59.3%,两组CR率和OR率差异无统计学意义(P>0.05)。主要不良反应为骨髓抑制和免疫功能抑制。31.3%(10/32)的患者出现Ⅲ～Ⅳ级粒细胞减少,9.4%(3/32)的患者出现Ⅲ～Ⅳ级血小板减少。有7例患者出现感染、发热,其中2例肺部感染患者死亡。非血液学毒性主要为胃肠道反应及轻度的肝肾功能损害。中位随访时间16个月(1～30个月),2年总生存(OS)率(93.8±4.2)%,2年疾病无进展生存(PFS)率(84.4±6.3)%。初发组2年OS率为100%,2年PFS率为(94.7±5.0)%;复发、难治组2年OS率为(76.9±11.3)%,2年PFS率为(69.2±12.3)%,两组差异无统计学意义(P>0.05)。结论氟达拉滨为主的化疗方案患者耐受性较好,对低度恶性淋巴瘤疗效较好,有可能改善患者的预后。     

Cyclophosphamide, mitoxantrone, vincristine and prednisone in the treatment of non-Hodgkin's lymphoma

Twenty-two patients with histologically confirmed non-Hodgkin's lymphoma received treatment with a chemotherapy combination containing cyclophosphamide, mitoxantrone, vincristine and prednisone. Leukopenia, nausea and vomiting were the most common side effects. A response rate of 77% (17 of 22 patients) was documented. These results indicate that the four-drug combination including mitoxantrone has good therapeutic activity in the treatment of non-Hodgkin's lymphoma.     

Mantle cell lymphoma

Opinion statement Mantle cell lymphoma is an aggressive non-Hodgkin’s lymphoma that remains incurable with current chemotherapeutic approaches. Despite response rates to many regimens of 50% to 70%, the disease typically progresses after chemotherapy with a median survival time of approximately 3 years. There is no clear standard approach for treating mantle cell lymphoma, making it critical that appropriate patients be enrolled in clinical trials. Off protocol, chemotherapy with chlorambucil, CVP (cyclophosphamide, vincristine, and prednisone), or CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) can be used in patients who are not candidates for aggressive therapy. Intensive combination chemotherapy regimens have high response rates and may prolong time to progressive disease. High-dose therapy with autologous stem cell transplantation may, but does not appear to, provide longer time to progression, although it may improve survival. For young patients with matched donors, allogeneic transplant is promising in the limited numbers of patients treated. Other agents, including rituximab, fludarabine, and cladribine, have demonstrated activity, but these agents do not appear to offer survival advantages over combination chemotherapy.     

New treatment options have changed the survival of patients with follicular lymphoma.

BACKGROUND: The natural history of follicular lymphoma is believed not to have changed over the last 30 years. Median survivals have ranged from 7 to 10 years, and the disease is considered incurable. However, multiple new treatment options have been developed in the last decade, and their impact on survival of follicular lymphoma remains unknown. PATIENTS AND METHODS: In the current analysis, we identified all previously untreated, advanced-stage, follicular lymphoma patients treated with the following three sequential treatment approaches: cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy +/- nonspecific immunostimulants (Southwest Oncology Group [SWOG] 7426 and 7713: 1974 to 1983); prednisone, methotrexate, doxorubicin, cyclophosphamide, and etoposide (ProMACE) plus mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) +/- interferon (SWOG 8809: 1988 to 1994); and CHOP followed by monoclonal antibody (MoAb) therapy (SWOG 9800 and 9911: 1998 to 2000). We assessed the patients' progression-free survival (PFS) and overall survival (OS). The MoAb trials included CHOP followed by rituximab (SWOG 9800) and CHOP followed by (131)I-tositumomab (SWOG 9911). RESULTS: The PFS curves for the CHOP and ProMACE-MOPP studies are overlapping, with 4-year PFS estimates of 46% and 48%, respectively. However, the PFS rate of the CHOP + MoAb studies is significantly improved at 61% (P = .005). The OS curves show improvement with each succeeding study. The 4-year estimate of OS is 69% for the CHOP regimens, 79% for the ProMACE-MOPP study, and 91% for the CHOP + MoAb regimens (P < .001). These conclusions were retained after adjusting for differences in prognostic factors between the study groups. CONCLUSION: The results of this study suggest that OS for patients with follicular lymphoma has improved over time and that the choice of initial therapy may matter.     

Treatment and prognosis of orbital non-Hodgkin's lymphomas.

Twenty patients with orbital lymphomas were treated and followed over a 14-year period. Ten of these patients had well-differentiated lymphocytic lymphoma (WDL), and all of them were clinical stage IE. Five patients had nodular poorly differentiated lymphocytic lymphomas (NPDL), three patients had diffuse histiocytic lymphomas (DHL), one had nodular mixed-cell lymphoma, and one had diffused mixed-cell lymphoma. The patients with WDL received local radiation therapy, and all of them entered completed remissions. The projected survival at 10 years was 100% for these patients. The patients with low-grade lymphomas with advanced disease were treated with chlorambucil and prednisone or cytoxan and vincristine. The patients with high-grade lymphomas received treatment with methotrexate, cyclophosphamide, doxorubicin, vincristine, bleomycin, dexamethasone (mBACOD) or cyclophosphamide, vincristine, methotrexate, cytosine arabinoside, leucovorin (COMLA). The overall survival estimate for all patients was 63% at 10 years. The disease-free survival was 49% at 10 years. The patients with high-grade lymphomas had a poor prognosis, with no survivors after 4 years. This study suggests that patients with WDL usually present with localized disease to the involved orbit, and have an excellent prognosis with radiation therapy alone. Patients with high-grade orbital non-Hodgkin's lymphomas have a poor outcome despite use of aggressive combination chemotherapy regimens.     

A comparative study of mitoxantrone and adriamycin in patients with non-Hodgkin's lymphoma: a preliminary result

In order to compare the efficacy and toxicity of mitoxantrone and adriamycin in non-Hodgkin's lymphoma, a randomized trial has been conducted by a cooperative study group since June 1984. Previously untreated patients with non-Hodgkin's lymphoma of intermediate-grade-malignancy were allocated to either MCOP (a combination of mitoxantrone, cyclophosphamide, vincristine, and prednisolone) or CHOP (a combination of adriamycin, cyclophosphamide, vincristine, and prednisolone) regimens. Forty-four patients were entered and 43 of these were fully evaluated for tumor response and toxicity. The complete remission rate was 80% for 20 patients receiving MCOP compared to 61% for 23 patients treated with CHOP. Response duration and overall survival were similar for the two treatments. Toxicity was almost comparable for the two treatments. Only alopecia was significantly less frequent in patients given MCOP than in those receiving CHOP. Mitoxantrone thus appears to be as effective as adriamycin in the treatment of non-Hodgkin's lymphoma.     

Long-term follow-up of a randomized trial of fludarabine-mitoxantrone, compared with cyclophosphamide, doxorubicin, vindesine, prednisone (CHVP), as first-line treatment of elderly patients with advanced, low-grade non-Hodgkin's lymphoma before the era of monoclonal antibodies.

BACKGROUND: This randomized study compared the efficacy and safety of fludarabine-mitoxantrone (FM) with mini-CHVP (cyclophosphamide, doxorubicin, vindesine, prednisone) in elderly patients with advanced, low-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS: End points were remission rates [overall response (OR) and complete response (CR)], failure-free survival (FFS), survival and toxicity. One hundred and fifty-five patients were randomized, 144 were evaluable for safety and 142 for response. Each treatment arm was given as six monthly cycles, followed by three bimonthly cycles. FM comprised fludarabine (20 mg/m(2) i.v.), days 1-5, plus mitoxantrone (10 mg/m(2) i.v.), day 1. CHVP cycles comprised cyclophosphamide (750 mg/m(2) i.v. infusion), doxorubicin (25 mg/m(2) i.v.) and vindesine (3 mg/m(2) i.v.) on day 1, and prednisone (50 mg/m(2)) on days 1-5. RESULTS: FM therapy resulted in superior remission rates (OR 81% versus 64%, CR 49% versus 17%; P = 0.0004). Median FFS for FM patients was 36 months, compared with 19 months for CHVP patients, and has not yet been reached for early CR patients at 53 months. Treatment arm was the major risk factor influencing survival. Both treatments were well tolerated, with only few infectious complications. CONCLUSION: FM was more effective than CHVP in achieving OR and CR, and favorably affected the outcome.     

Pilot study of modified version of CHOP plus radiotherapy for early-stage aggressive non-Hodgkin's lymphoma of the head and neck

PURPOSE: To evaluate the safety and efficacy of a modified version of cyclophosphamide, doxorubicin, vincristine, prednisone (pirarubicin, cyclophosphamide, vincristine, and prednisone [THP-COP]) plus radiotherapy for early-stage aggressive non-Hodgkin's lymphoma of the head and neck. METHODS AND MATERIALS: Between December 1993 and December 1999, 41 patients with early-stage non-Hodgkin's lymphoma with intermediate-grade histologic features were enrolled in our study. The mean patient age was 51 years. Of the 41 patients, 27 had Stage I and 14 Stage II disease. The primary site was Waldeyer's ring, a neck node, or an extranodal site in 14, 11, and 16 patients, respectively. The immunophenotype was B cell in 29 and T cell in 12 patients. All patients were in the low-risk category according to the International Prognostic Index. Chemotherapy consisted of 40 mg/m(2) i.v. pirarubicin (THP-Adriamycin), 750 mg/m(2) i.v. cyclophosphamide, and 1.0 mg/m(2) i.v. vincristine, on Day 1 and 40 mg/m(2) p.o. prednisone on Days 1-5. The combination chemotherapy was given twice at a 14-day interval. Radiotherapy was given to involved areas at a fraction size of 2.0-2.5 Gy up to a total of 40 Gy within 4-5 weeks. The mean follow-up period was 63 months. RESULTS: The 5-year overall survival rate was 89%. The 5-year cause-specific survival and progression-free survival rate was 90% and 81%, respectively. The 5-year progression-free survival rate for patients with Waldeyer's ring primaries was 93%. Patients with tumor <5 cm in size had greater 5-year progression-free survival than those with tumor >5 cm in size (85% vs. 33%, p <0.05, log-rank test). Grade 4 neutropenia was seen in 12% of patients; however, 93% of patients (38 of 41) received chemotherapy as scheduled with the support of granulocyte colony-stimulating factor. CONCLUSION: Biweekly THP-COP plus radiotherapy is feasible and effective for Stage I-II low-risk non-Hodgkin's lymphoma.