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Andreas Engert - One of the best experts on this subject based on the ideXlab platform.
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ABVD or BEACOPP for Advanced Hodgkin Lymphoma
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015Co-Authors: Andreas EngertAbstract:The development of multiagent chemotherapy dramatically changed the prognosis of patients with advanced-stage Hodgkin lymphoma (HL). Although almost all of these patients died when treated with radiotherapy or single-agent chemotherapy, the fourdrug regimen MOPP (mustargen, oncovin, Procarbazine, and prednisone) led to remission rates of more than 50% and an overall survival (OS) rate of more than 60%. Shortly thereafter, ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) as an alternative anthracycline-containing regimen was introduced in the treatment of HL. It took 20 years before ABVD was accepted as better than MOPP or MOPP-based hybrid variants. In the meantime, multiagent regimens such as ChlVPP (chlorambucil, vinblastine, Procarbazine, and prednisolone) plus EVA (etoposide, vinblastine, and doxorubicin) and Stanford V were evaluated but failed to improve outcomes of patients with advanced-stage HL. The quest for a more effective regimen in HLwas the rationale for the GermanHodgkin StudyGroup (GHSG) to design BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, Procarbazine, and prednisone)more than 20 years ago. This regimen was developed using baseline (BEACOPPbaseline) or escalated doses (BEACOPPescalated) and subsequently compared with the GHSG standard at that time, COPP (cyclophosphamide, vincristine, Procarbazine, and prednisone) –ABVD, in the HD9 trial. With a total of 1,195 randomly assigned patients and 5 years of follow-up, BEACOPPescalated was found to be significantly better than BEACOPPbaseline and COPP-ABVD. The 10-year update confirmed and extended the initial findings, demonstrating an improvement of 18% in tumor control between BEACOPPescalated and COPP-ABVD as well as an OS difference of 11%. Because BEACOPPescalated was also associated withmore hematologic toxicity, infections, infertility, and secondary leukemia, there has been some controversy about this regimen since the initial publication. Themajority of patients treated with BEACOPPescalated in HD9 developed grade 3 to 4 leucopenia and thrombocytopenia, and 22% had infectious complications. However, this did not translate into higher treatment-associated mortality with BEACOPPescalated, as compared with the other two arms of the HD9 trial, BEACOPPbaseline and COPP-ABVD. In the 10-year update, the higher response rates in patients treated with BEACOPPescalated resulted in significantly lower overall mortality (12%) as compared with those in patients treated with BEACOPPbaseline (19%) or COPP-ABVD (24%). With this clear improvement in efficacy, the GHSG HD12 follow-up trial for advanced-stage HL aimed at reducing overall toxicity of BEACOPP by employing four cycles of BEACOPPescalated followed by four cycles of BEACOPPbaseline (ie, 41 4). However, this approach failed. It was the next-generation trial in advanced-stage HL, HD15, in which more than 2,100 patients were randomly assigned, that demonstrated the reduction to six cycles of BEACOPPescalated followed by radiation administered to residual positron emission tomography (PET) –positive disease $ 2.5 cm led to a significantly improved and less toxic regimen. With the disappearance of potential alternatives such as Stanford V, the choice of the best treatment for advanced-stage HL increasingly focused on the question of ABVD or BEACOPP. Subsequently, collaborative groups directly compared ABVD with BEACOPPescalated in four prospective trials. 10-13 Instead of using eight cycles of BEACOPPescalated, as in HD9, three of these trials used 41 4, similar to the experimental arms of the HD12 trial; the Italian HD2000 instead used four cycles of BEACOPPescalated followed by two cycles of BEACOPPbaseline (4 1 2). In these four trials, a total of 1,227 patients were randomly assigned to 41 4 or 4 1 2 BEACOPP variants and ABVD. All four trials reported significant improvements in tumor control, with 5-year progression-free survival (PFS) gains ranging between 12% and 18% and OS differences of 4% to 8% favoring BEACOPP. In the article accompanying this editorial, Merli et al report an update of their 2009 publication of the Italian HD2000 trial. This three-arm randomized trial registered 307 patients with HL, of whom 12 were subsequently excluded. The initial article, with a median follow-up of 42 months, also published in Journal of Clinical Oncology, had shown a significantly better PFS with BEACOPP 4 1 2 as compared with ABVD (81% v 68% P 5 .038). In the 10-year update, with a median follow-up of 120 months, PFS with ABVD, BEACOPP 4 1 2, and the 10-drug COPP-EBV-CAD (cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, Procarbazine, vinblastine, and bleomycin) regimen was 69%, 75%, and 76%, respectively, with corresponding OS rates of 85%, 84%, and 86%. A total of 13 secondary neoplasias were reported, one after treatment with ABVD, six after BEACOPP, and six after COPP-EBV-CAD. The authors concluded that with longer follow-up, they were no longer able to confirm the superiority of BEACOPP 4 1 2 over ABVD in terms of PFS and that this was mainly because of higher mortality from secondary malignancies. However, with fewer
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is there a role for beacopp bleomycin etoposide adriamycin cyclophosphamide vincristine Procarbazine prednisone in relapsed hodgkin lymphoma
Leukemia & Lymphoma, 2009Co-Authors: Dennis A Eichenauer, Andreas EngertAbstract:The BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, Procarbazine, prednisone) regimen was originally developed to improve the first-line treatment of advanced Hodgkin lymp...
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escalated dose beacopp in the treatment of patients with advanced stage hodgkin s lymphoma 10 years of follow up of the ghsg hd9 study
Journal of Clinical Oncology, 2009Co-Authors: Andreas Engert, Jeremy Franklin, Michael Pfreundschuh, Bernd Dorken, Andreas Lohri, Wolfdieter Ludwig, Peter Paul Koch, Mathias Hanel, Martin WilhelmAbstract:Purpose The HD9 trial of the German Hodgkin Study Group compared two different doses (baseline and escalated) of the bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, Procarbazine, and prednisone (BEACOPP) chemotherapy regimen in 1,196 patients with advanced-stage Hodgkin's lymphoma (HL). The previous analysis with 5 years median follow-up had indicated improved tumor control with BEACOPP escalated. Since the long-term safety and efficacy of this regimen has been debated, we report the 10-year follow-up. Patients and Methods Patients received one of three chemotherapy regimens: eight cycles of cyclophosphamide, vincristine, Procarbazine, and prednisone (COPP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); eight cycles of BEACOPP baseline; or eight cycles of BEACOPP escalated. Results Median follow-up was 111 months. At 10 years, freedom from treatment failure (FFTF) was 64%, 70%, and 82% with OS rates of 75%, 80%, and 86% for patients treated with COPP/ABVD (...
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population pharmacokinetics of the beacopp polychemotherapy regimen in hodgkin s lymphoma and its effect on myelotoxicity
Clinical Pharmacokinectics, 2007Co-Authors: S. Wilde, Andreas Engert, A. Jetter, S. Rietbrock, D. Kasel, Georg Hempel, S. Reif, Andreas Josting, Beate Klimm, U. JaehdeAbstract:Background and objective The BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, Procarbazine and prednisone) chemotherapy regimen for the treatment of advanced Hodgkin’s lymphoma has a superior outcome, but its toxicity (mainly haematotoxicity) is pronounced and highly variable. The present study was conducted to address the role of pharmacokinetics in individual toxicity.
Jurgen Finke - One of the best experts on this subject based on the ideXlab platform.
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immunochemotherapy with rituximab methotrexate Procarbazine and lomustine for primary cns lymphoma pcnsl in the elderly
Annals of Oncology, 2011Co-Authors: Kristina Fritsch, Gabriele Ihorst, Jurgen Finke, Benjamin Kasenda, Claudia Hader, Guido Nikkhah, Marco Prinz, Vanessa Haug, S Haug, Gerald IllerhausAbstract:Abstract Background Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal non-Hodgkin lymphoma confined to the central nervous system. In this article, we report the results of a pilot trial adding rituximab to the established regimen consisting of methotrexate, Procarbazine, and lomustine (R-MCP). Design and methods PCNSL patients ≥65 years without Karnofsky performance score (KPS) limit were included. R-MCP regimen consisted of rituximab (375 mg/m2 i.v. on days -6, 1, 15, and 29), methotrexate (3 g/m2 i.v., days 2, 16, and 30) followed by folinic rescue, Procarbazine (60 mg/m2 orally, days 2–11), and lomustine (110 mg/m2 orally, day 2). A maximum of three 43-day cycles were applied. Primary end point was response to treatment obtained by magnetic resonance imaging. Secondary end points were overall survival (OS) and progression-free survival (PFS). Results Twenty-eight patients were included (median age 75, median KPS 60%). Best documented response: complete remission in 18 of 28 (64%), partial remission in 5 of 28 (18%), stable disease in 1 of 28 (4%), and progressive disease in 2 of 28 (7%) patients. Response was not assessed in two patients. Two treatment-associated deaths were observed. After a median follow-up of 36 months, the 3-year PFS and OS was 31%. Conclusion R-MCP regimen is well tolerated and active in elderly patients with newly diagnosed PCNSL.
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high dose methotrexate combined with Procarbazine and ccnu for primary cns lymphoma in the elderly results of a prospective pilot and phase ii study
Annals of Oncology, 2008Co-Authors: Gerald Illerhaus, Reinhard Marks, Fabian Muller, Gabriele Ihorst, Friedrich Feuerhake, Martina Deckert, Christoph B Ostertag, Jurgen FinkeAbstract:Abstract Background To improve survival of elderly patients with primary central nervous system lymphoma (PCNSL), we conducted a phase II study with high-dose methotrexate (MTX) combined with Procarbazine and CCNU. To reduce neurotoxicity, whole-brain irradiation was reserved for patients not responding to chemotherapy. Patients and methods High-dose MTX was applied on days 1, 15, and 30, Procarbazine on days 1–10, and CCNU on day 1. Study treatment comprised up to three 45-day cycles. There was no lower limit of Karnofsky performance status (KPS). Results Thirty patients with PCNSL (n = 29) or primary ocular lymphoma (n = 1) were included (median age 70 years, range 57–79 years). The median initial KPS was 60% (range 30%–90%). Best documented response in 27 assessable patients were 12 of 27 (44.4%) complete remissions, 7 of 27 (25.9%) partial remissions, and 8 of 27 (29.6%) disease progressions. Two patients died of probable treatment-related causes. With a median follow-up of 78 months (range 34–105), the 5-year overall survival is 33%. Eight of 30 patients (26.7%) are currently alive and well, six without signs of leukoencephalopathy. Conclusion The combination of high-dose MTX with Procarbazine and CCNU is feasible and effective and results in a low rate of leukoencephalopathy. Comorbidity and toxicity remain of concern when treating PCNSL in elderly patients.
Gerald Illerhaus - One of the best experts on this subject based on the ideXlab platform.
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immunochemotherapy with rituximab methotrexate Procarbazine and lomustine for primary cns lymphoma pcnsl in the elderly
Annals of Oncology, 2011Co-Authors: Kristina Fritsch, Gabriele Ihorst, Jurgen Finke, Benjamin Kasenda, Claudia Hader, Guido Nikkhah, Marco Prinz, Vanessa Haug, S Haug, Gerald IllerhausAbstract:Abstract Background Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal non-Hodgkin lymphoma confined to the central nervous system. In this article, we report the results of a pilot trial adding rituximab to the established regimen consisting of methotrexate, Procarbazine, and lomustine (R-MCP). Design and methods PCNSL patients ≥65 years without Karnofsky performance score (KPS) limit were included. R-MCP regimen consisted of rituximab (375 mg/m2 i.v. on days -6, 1, 15, and 29), methotrexate (3 g/m2 i.v., days 2, 16, and 30) followed by folinic rescue, Procarbazine (60 mg/m2 orally, days 2–11), and lomustine (110 mg/m2 orally, day 2). A maximum of three 43-day cycles were applied. Primary end point was response to treatment obtained by magnetic resonance imaging. Secondary end points were overall survival (OS) and progression-free survival (PFS). Results Twenty-eight patients were included (median age 75, median KPS 60%). Best documented response: complete remission in 18 of 28 (64%), partial remission in 5 of 28 (18%), stable disease in 1 of 28 (4%), and progressive disease in 2 of 28 (7%) patients. Response was not assessed in two patients. Two treatment-associated deaths were observed. After a median follow-up of 36 months, the 3-year PFS and OS was 31%. Conclusion R-MCP regimen is well tolerated and active in elderly patients with newly diagnosed PCNSL.
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high dose methotrexate combined with Procarbazine and ccnu for primary cns lymphoma in the elderly results of a prospective pilot and phase ii study
Annals of Oncology, 2008Co-Authors: Gerald Illerhaus, Reinhard Marks, Fabian Muller, Gabriele Ihorst, Friedrich Feuerhake, Martina Deckert, Christoph B Ostertag, Jurgen FinkeAbstract:Abstract Background To improve survival of elderly patients with primary central nervous system lymphoma (PCNSL), we conducted a phase II study with high-dose methotrexate (MTX) combined with Procarbazine and CCNU. To reduce neurotoxicity, whole-brain irradiation was reserved for patients not responding to chemotherapy. Patients and methods High-dose MTX was applied on days 1, 15, and 30, Procarbazine on days 1–10, and CCNU on day 1. Study treatment comprised up to three 45-day cycles. There was no lower limit of Karnofsky performance status (KPS). Results Thirty patients with PCNSL (n = 29) or primary ocular lymphoma (n = 1) were included (median age 70 years, range 57–79 years). The median initial KPS was 60% (range 30%–90%). Best documented response in 27 assessable patients were 12 of 27 (44.4%) complete remissions, 7 of 27 (25.9%) partial remissions, and 8 of 27 (29.6%) disease progressions. Two patients died of probable treatment-related causes. With a median follow-up of 78 months (range 34–105), the 5-year overall survival is 33%. Eight of 30 patients (26.7%) are currently alive and well, six without signs of leukoencephalopathy. Conclusion The combination of high-dose MTX with Procarbazine and CCNU is feasible and effective and results in a low rate of leukoencephalopathy. Comorbidity and toxicity remain of concern when treating PCNSL in elderly patients.
Jun Ichi Kuratsu - One of the best experts on this subject based on the ideXlab platform.
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prognostic impact of completion of initial high dose methotrexate therapy on primary central nervous system lymphoma a single institution experience
International Journal of Clinical Oncology, 2015Co-Authors: Keishi Makino, Hideo Nakamura, Takuichiro Hide, Jun Ichiro Kuroda, Shigetoshi Yano, Jun Ichi KuratsuAbstract:Background This retrospective single-center study assessed the feasibility, outcomes, and side-effects of high-dose methotrexate (HD-MTX) plus Procarbazine in the treatment of immunocompetent patients with primary central nervous system lymphoma (PCNSL).
Nobuyoshi Sasaki - One of the best experts on this subject based on the ideXlab platform.
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consecutive single institution case series of primary central nervous system lymphoma treated by r mpv or high dose methotrexate monotherapy
Japanese Journal of Clinical Oncology, 2020Co-Authors: Nobuyoshi Sasaki, Keiichi Kobayashi, Kuniaki Saito, Saki Shimizu, Kaori Suzuki, Jeunghun Lee, Yuki Yamagishi, Junji Shibahara, Nobuyuki TakayamaAbstract:OBJECTIVE The optimal regimen for use of high dose-methotrexate-based chemotherapy in primary central nervous system lymphoma is still under debate. We conducted a retrospective study to evaluate the treatment outcome of a combination immunochemotherapy consisting of rituximab, methotrexate, Procarbazine and vincristine followed by with or without whole brain radiotherapy and consolidation cytarabine, in comparison with high dose-methotrexate monotherapy followed by full dose whole brain radiotherapy. METHODS Newly diagnosed primary central nervous system lymphoma patients treated with either rituximab, methotrexate, Procarbazine and vincristine or high dose-methotrexate in Kyorin University Hospital were identified, and the response rates and survival were compared. Toxicities, post-treatment transition of Mini-Mental State Examination, Karnofsky performance status score, Fazekas scale and prognostic factors were analysed in the rituximab, methotrexate, Procarbazine and vincristine group. RESULTS Ninety-five patients treated with rituximab, methotrexate, Procarbazine and vincristine (n = 39) or high dose-methotrexate (n = 56) were analysed. The complete response/complete response unconfirmed rate was significantly higher in the rituximab, methotrexate, Procarbazine and vincristine group (74.4 vs. 15.4%, P < 0.001). Accordingly, both median progression-free survival and overall survival were significantly longer in the rituximab, methotrexate, Procarbazine and vincristine group (median progression-free survival: unreached vs. 14.75 months, P < 0.001) (median overall survival: unreached vs. 63.15 months, P = 0.005). Although the rate of grade 3/4 hematologic toxicities was high both during rituximab, methotrexate, Procarbazine and vincristine and consolidation cytarabine, the rate of grade 3/4 infections was low, and no treatment related deaths were observed. Deterioration in Karnofsky performance status or Mini-Mental State Examination was rare, except on disease recurrence. Although whole brain radiotherapy was associated with Fazekas scale deterioration, its association with Karnofsky performance status or Mini-Mental State Examination deterioration was not significant. CONCLUSIONS Rituximab, methotrexate, Procarbazine and vincristine was apparently promising in comparison with high dose-methotrexate monotherapy with manageable toxicity in this retrospective study, and further investigation is warranted.