Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to evaluate the role of Mitoxantrone in the therapy of non-Hodgkin's lymphoma (NHL) (intermediate-high grade malignancy) a series of successive phase II-III studies were performed in a multicenter cooperative group. The first phase II study consisted of Mitoxantrone alone administered at 14 mg/m2 i.v. on day 1 and repeated every 3 weeks for six times. Fifteen refractory or relapsed patients (pts) entered the study, and an overall response of 54% (CR 4 pts, PR 4 pts) was obtained. 7 pts progressed or remained stable disease (NR). The second phase II consisted of Mitoxantrone in combination with Etoposide and Prednisone (VeMP). Twenty pts were treated and a complete remission (CR) of 50% with 1 partial remission (PR) were obtained with an overall response of 55%. The third phase II study consisted of 13 pts with refractory or relapsed disease treated with Mitoxantrone, Cis-platinum, Etoposide and Prednisone (CEMP); an overall response of 62% was obtained with an acceptable toxicity. This was not superior to other conventional salvage regimens. On this background a phase III study with VEMP (Etoposide, Cyclophosphamide, Mitoxantrone, Prednisone) was started as first line therapy for pts presenting one or more of following criteria: Performance Status (P.S.) 2-3, aggressive histology at stage I-IIE or advanced stage in old pts, low grade histology with B-symptoms stage in III-IV, age over 65 years. Until now 64 pts entered this study.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The rationale of therapy with mitoxantrone in non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Co-operative Study Group, (NHLCSG) Italy. 847 3

Many chemotherapeutic regimens will induce remission in dogs with lymphoma, but almost all dogs suffer relapse. Mitoxantrone was selected for evaluation as single-agent chemotherapy for relapsing canine lymphoma based on its use in humans undergoing salvage chemotherapy for non-Hodgkin's lymphoma and its tumoricidal effect against canine lymphoma. Dogs entered into study had multicentric lymphoma, and all had been treated solely with a standard combination chemotherapy protocol. At 1st relapse, all dogs were again staged and underwent lymph node biopsy. Mitoxantrone was administered IV at 6 mg/m2 every 21 days. Dogs were evaluated for lymphadenopathy before each dose of mitoxantrone. Fifteen dogs were entered into study. The average age (+/- SEM) of the dogs studied was 7.7 +/- 0.91 years, and most dogs were large (mean +/- SEM weight, 24.44 +/- 2.15 kg). Twelve dogs (80%) had B-cell lymphoma, and 3 had T-cell lymphoma. Dogs were staged IV (n = 12) or V (n = 3). The median duration of chemotherapy before entry into the study was 98 days. Overall median duration of response after mitoxantrone chemotherapy was 21 days. Complete responses were attained in 7 of 15 dogs (47%) with a median response duration of 84 days. Nine of 15 (60%) dogs attained a complete remission with additional chemotherapy after failing mitoxantrone chemotherapy. Mild toxicities were observed after mitoxantrone administration. No adverse reactions were observed during mitoxantrone infusions. The results of this study demonstrate that mitoxantrone, as a single agent, has limited value for dogs with lymphoma at 1st relapse after conventional multidrug chemotherapy.
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PMID:Evaluation of single-agent mitoxantrone as chemotherapy for relapsing canine lymphoma. 977 7

Patients with recurrent or refractory Hodgkin's and non-Hodgkin's lymphoma are increasingly being treated with high-dose therapy and hematopoietic cell transplantation. As minimal disease status at the time of transplant has been a repeatedly proven significant prognostic factor for long-term survival, effective initial cytoreduction is an important step in the process. Modern chemotherapy programs for Hodgkin's lymphoma include virtually all active agents and little is left for effective salvage. Mitoxantrone is an active agent in lymphoma that is not generally used in first-line treatment. The aim of this study was to determine toxicity and response rate to CN3OP (fractionated mitoxantrone 6 mg/m2 on days 1, 2, and 3, combined with standard dose cyclophosphamide, vincristine, and prednisone) in 44 patients with relapsed or refractory lymphoma. Most of patients had advanced disease and one or more extranodal sites at relapse. Median response duration to immediate past therapy was four months, and one third of patients had not responded to prior treatment. A median of 4 cycles of CN3OP were given per patient for a total of 173 cycles. Grade III-IV neutropenia occured in 53% of cycles, Grade I-III mucositis in 24%, and Grade I-III infection in 17% of cycles. Of 34 evaluable patients with Hodgkin's lymphoma 12 (35%) achieved complete remission (CR) and 15 (44%) partial remission (PR) for an overall response rate of 79%. Two of five evaluable non-Hodgkin's lymphoma patients responded with PR. Median overall survival and event free survival in the entire group was 29 months and 11 months respectively. At this time 16 patients have died; 12 of lymphoma, two of unknown cause and two of other causes. Complete response to CN3OP correlated with survival. CN3OP is an effective and safe regimen for cytoreduction in Hodgkin's lymphoma patients pretreated with doxorubicin/alkylator/etoposide-containing primary therapies.
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PMID:CN3OP: an active regimen in patients with relapsed/refractory Hodgkin's lymphoma. 1096 30

We have evaluated the clinico-pathological and therepeutical outcome of patients aged 70 and older with malignant lymphomas treated at a single institute over a 20-year period of time. Among the several studies evaluated, the most important is a prospective randomized study comparing a new regimen, VMP (VP 16, Mitoxantrone and Prednimustine) vs the goal standard CHOP in unfavorable non-Hodgkin's lymphoma (NHL), showing that CHOP is significantly better than VMP in terms of objective response rate, progression free and overall survival. Therefore CHOP remains the standard regimen also for patients of over 70 years of age and stage II--IV intermediate and high grade NHL.
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PMID:A 20-year experience on malignant lymphomas in patients aged 70 and older at a single institute. 1116 89

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.
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PMID:The role of mitoxantrone in non-Hodgkin's lymphoma. 1201 36

Mitoxantrone and Epirubicin are active agents in non-Hodgkin's lymphomas (NHL). These drugs have reduced cardiotoxicity and therefore are indicated in treatment of elderly patients. Cyclophosphamide, mitoxantrone, vincristine and methylprednisone (CNOP) and cyclophosphamide, epirubicin, vincristine and methylprednisone (CEOP) are combination chemotherapy and contain Mitoxantrone and Epirubicin that have been shown to be effective in treatment of NHL of intermediate and highgrade of malignancy in the elderly. Since Mitoxantrone and Epirubicin are partially non-cross resistant their combined use may diminish emergence of resistant neoplastic clones and may be associated with enhanced anti-neoplastic activity. In this study, a polychemotherapy schedule alternating 3 cycles of CEOP and 3 cycles of CNOP, was used in a single center between December 1988 and April 1995 to treat 41 previously untreated patients, over 60 years of age affected by intermediate or high grade non-Hodgkin's lymphoma according to the Working Formulation. In treated patients, 57.5% achieved complete response, 35% partial response and 7.5% were non-responders. Overall survival was 52.4 % at 4 years, Disease free survival (DFS) for complete responders was 48.9%. Only one case of severe extrahematological toxicity (grade 3-4 WHO) was observed. Severe mucositis (grade 3-4 WHO) was absent, and delayed administration of chemotherapy was required in only 7/230 cycles. No treatment related deaths were registered. This regimen achieved results comparable to that of other anthracycline or mitoxantrone based chemotherapy, but determined lower toxicity. Alternating CEOP and CNOP may improve overall toxicity.
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PMID:Alternation of epirubicin and mitoxantrone in CHOP-like regimens retains efficacy and reduces overall toxicity in elderly patients with high and intermediate grade non-Hodgkin lymphomas. 1261 18

The standard CHOP regimen may cure 30-40% of patients with advanced aggressive non-Hodgkin's lymphoma (ANHL). Mitoxantrone is an anthracenedione, which is active in NHL and its toxicity profile may be more favorable than doxorubicin with respect to alopecia, mucositis and cardiotoxicity. This study was designed to compare the effectiveness of an escalated dose of mitoxantrone with that of standard doxorubicin, used in the CHOP regimen in patients with ANHL. One hundred and forty three eligible patients with ANHL were randomized to receive 6 cycles of either CHOP (n = 71) or intensified CNOP (iCNOP) (n = 72), with mitoxantrone 20 mg/m2, i.v., d.1 instead of doxorubicin. Complete responders (CR) were again randomized either to receive interferon-alpha (IFN-alpha) maintenance (3 MU t.i.w., s.c.) or not. The CR rate was 70 vs. 76% for iCNOP and CHOP (p = 0.45), and the overall response rate was 81 vs. 83%, respectively (p = 0.71). The 5-year failure free survival (FFS) was 48 and 50% in the iCNOP and CHOP arm, respectively (p = 0.45), and the 5-year overall survival (OS) was 61 vs. 64% (p = 0.56). IFN-alpha did not prolong relapse free survival (p = 0.91). iCNOP produced less alopecia (p = 0.001) but more febrile episodes (p = 0.04) than CHOP, while requiring more frequent G-CSF support (p = 0.01). Two cases of acute myelogenous leukemia (AML) were recorded, both in the iCNOP arm (p = 0.14). In conclusion, iCNOP was equally effective to CHOP in patients with ANHL, producing more leukopenia and febrile episodes, but less alopecia. The development of two cases of secondary AML in th e iCNOP arm is of concern.
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PMID:A randomized trial comparing intensified CNOP vs. CHOP in patients with aggressive non-Hodgkin's lymphoma. 1276 40

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.
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PMID:The role of mitoxantrone in the treatment of indolent lymphomas. 1570 17

This paper presents a summary of the evidence review group report into the clinical effectiveness and cost-effectiveness of rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin's lymphoma (NHL), in accordance with the licensed indication, based upon the evidence submission from Roche Products Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submitted clinical evidence included two randomised controlled trials [European Organisation for Research and Treatment of Cancer (EORTC) and German Low Grade Lymphoma Study Group - Fludarabine, Cyclophosphamide and Mitoxantrone and (GLSG-FCM)] comparing the clinical effects of chemotherapy with or without rituximab in the induction of remission at first or second relapse and the clinical benefits of rituximab maintenance therapy versus the NHS's current clinical practice of observation for follicular lymphoma (FL) patients. Both trials showed that in patients with relapsed FL the addition of rituximab to chemotherapy induction treatment increased overall response rates. Furthermore, rituximab maintenance therapy increased the median length of remission when compared with observation only. Safety data from the two trials showed that while the majority of patients reported some adverse events, the number of patients withdrawing from treatment in the EORTC trial was low, with rates not being reported for the GLSG-FCM trial. The most commonly reported adverse events were blood/bone marrow toxicity, skin rashes and allergies. The ERG reran the manufacturer's economic model after altering several of the assumptions and parameter values in order to recalculate the cost-utility ratios, quality-adjusted life-years (QALYs) and estimates of benefits. The manufacturer reported that maintenance therapy with rituximab was cost-effective compared with observation against commonly applied thresholds, with an incremental cost-effectiveness ratio of 7721 pounds per QALY gained. The greatest clinical effectiveness is achieved by R-CHOP followed by rituximab maintenance (R-CHOP>R) and this treatment strategy had the greatest probability of being cost-effective for a QALY of approximately 18,000 pounds or greater. The guidance issued by NICE as a result of the STA states that in people with relapsed stage III or IV follicular NHL, rituximab is now an option in combination with chemotherapy to induce remission or alone as maintenance therapy during remission. Rituximab monotherapy is also an option for people with relapsed or refractory disease when all alternative treatment options have been exhausted.
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PMID:Rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin's lymphoma. 1980 88


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