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Gemcitabine DLBCL

Alden A Moccia, Felicitas Hitz, Paul Hoskins, Richard Klasa, Maryse M Power, Kerry J Savage, Tamara Shenkier, John D Shepherd, Graham W Slack, Kevin W Song, Randy D Gascoyne, Joseph M Connors, Laurie H Sehn
The optimal choice of salvage therapy for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) remains unknown. Based on promising results of phase II trials, the preferred salvage regimen in British Columbia since 2002 has been the out-patient regimen, gemcitabine, dexamethasone, and cisplatin (GDP). We conducted a retrospective analysis including all patients with relapsed/refractory DLBCL or HL who received GDP as salvage therapy between September 2002 and June 2010...
June 27, 2016: Leukemia & Lymphoma
Yago Nieto, Benigno C Valdez, Peter F Thall, Roy B Jones, Wei Wei, Alan Myers, Chitra Hosing, Sairah Ahmed, Uday Popat, Elizabeth J Shpall, Muzaffar Qazilbash, Alison Gulbis, Paolo Anderlini, Nina Shah, Qaiser Bashir, Amin Alousi, Yasuhiro Oki, Michelle Fanale, Bouthaina Dabaja, Chelsea Pinnix, Richard Champlin, Borje S Andersson
BACKGROUND: More active high-dose chemotherapy (HDC) regimens are needed for refractory lymphomas. The authors previously combined infusional gemcitabine with busulfan and melphalan (Gem/Bu/Mel) pursuing DNA damage repair inhibition. Subsequently, they combined Gem/Bu/Mel with vorinostat, which facilitates chemotherapy access to DNA. The resulting regimen was safe and synergistic. However, vorinostat induced DNA methyltransferase up-regulation, which could be preclinically abrogated by azacitidine, increasing tumor-cell kill...
September 1, 2016: Cancer
Kazumi Hayashi, Eijiro Nagasaki, Shin Kan, Masaki Ito, Yuko Kamata, Sadamu Homma, Keisuke Aiba
Although rituximab, a chimeric monoclonal antibody that specifically binds to CD20, has significantly improved the prognosis for diffuse large B cell lymphoma (DLBCL), one-third of DLBCL patients demonstrate resistance to rituximab or relapse after rituximab treatment. Thus, a novel approach to rituximab-based treatment is likely to be required to improve the efficacy of DLBCL treatment. As complement dependent cytotoxicity (CDC) is a key mechanism mediating rituximab's tumoricidal activity, rituximab binding to CD20 on tumor cells is a critical factor for effective rituximab-based treatments against DLBCL...
May 2016: Cancer Science
John Kuruvilla, David A MacDonald, C Tom Kouroukis, Matthew Cheung, Harold J Olney, A Robert Turner, Peter Anglin, Matthew Seftel, Walid Sabry Ismail, Stefano Luminari, Stephen Couban, Tara Baetz, Ralph M Meyer, Annette E Hay, Lois Shepherd, Marina S Djurfeldt, Sameer Alamoudi, Bingshu E Chen, Michael Crump
The treatment of transformed indolent lymphoma (TRIL) often includes salvage chemotherapy (SC) and autologous stem cell transplant (ASCT). NCIC CTG LY12 is a randomized phase 3 trial comparing gemcitabine, dexamethasone, and cisplatin (GDP) with dexamethasone, cytarabine, and cisplatin (DHAP) before ASCT. This analysis compares the results of SC and ASCT for TRIL with de novo diffuse large B-cell lymphoma (DLBCL). Six-hundred nineteen patients with relapsed/refractory aggressive non-Hodgkin lymphoma were randomized to GDP or DHAP; 87 patients (14%) had TRIL and 429 (69%) had DLBCL...
August 6, 2015: Blood
Sarah Barton, Eliza A Hawkes, David Cunningham, Clare Peckitt, Sue Chua, Andrew Wotherspoon, Ayoma Attygalle, Alan Horwich, Mike Potter, Mark Ethell, Claire Dearden, Mary Gleeson, Ian Chau
BACKGROUND: Patients with relapsed diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Gemcitabine, methylprednisolone, cisplatin +/- rituximab (GEM-P+/-R) is a salvage regimen with limited overlap in toxicity with first-line therapy and short duration of inpatient delivery. METHODS: We assessed the efficacy and safety of GEM-P+/-R in a retrospective single-centre analysis including patients meeting criteria of ≥ 18 yr of age, histologically proven DLBCL, treated between 2001 and 2011 in second-line with gemcitabine 1000 mg/m(2) day 1, 8 and 15, methylprednisolone 1000 mg day 1-5, cisplatin 100 mg/m(2) day 15 (replaced with carboplatin AUC5 if contraindication/toxicity) +/- rituximab 375 mg/m(2) day 1 and 15, every 28 d...
March 2015: European Journal of Haematology
Paul A Fields, William Townsend, Andrew Webb, Nicholas Counsell, Christopher Pocock, Paul Smith, Andrew Jack, Nadjet El-Mehidi, Peter W Johnson, John Radford, David C Linch, David Cunnningham
PURPOSE: The treatment of patients with diffuse large B-cell lymphoma (DLBCL) with cardiac comorbidity is problematic, because this group may not be able to receive anthracycline-containing chemoimmunotherapy. We designed a single-arm phase II multicenter trial of rituximab, gemcitabine, cyclophosphamide, vincristine, and prednisolone (R-GCVP) in patients considered unfit for anthracycline-containing chemoimmunotherapy because of cardiac comorbidity. PATIENTS AND METHODS: Sixty-one of 62 patients received R-GCVP, administered on day 1 with gemcitabine repeated on day 8 of a 21-day cycle...
February 1, 2014: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Andrew M Evens, Steven T Rosen, Irene Helenowski, Justin Kline, Annette Larsen, Jennifer Colvin, Jane N Winter, Koen M van Besien, Leo I Gordon, Sonali M Smith
There remains an unmet therapeutic need for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL). We conducted a phase I/II trial with bortezomib (dose-escalated to 1·6 mg/m(2) ) given concurrently with gemcitabine (800 mg/m(2) ) days 1 + 8 q21 d. Of 32 patients, 16 each had relapsed/refractory PTCL and DLBCL. Median prior therapies were 3 and 35% had failed transplant. Among the first 18 patients, 67% experienced grade 3/4 neutropenia and/or grade 3/4 thrombocytopenia resulting in repeated treatment delays (relative dose intensity: 46%)...
October 2013: British Journal of Haematology
Andres Forero-Torres, Nancy Bartlett, Anne Beaven, Han Myint, Sunita Nasta, Donald W Northfelt, Nancy C Whiting, Jonathan G Drachman, Albert F Lobuglio, Craig H Moskowitz
Dacetuzumab, a CD40-targeted, humanized antibody, mediates antitumor activity through effector cell functions and direct apoptotic signal transduction. Preclinical studies demonstrated synergistic activity between dacetuzumab, gemcitabine and rituximab against non-Hodgkin lymphoma in vivo. A phase 1b safety/efficacy study of dacetuzumab in combination with rituximab and gemcitabine was conducted in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Patients received dacetuzumab at doses of 8 or 12 mg/kg IV weekly with rituximab (375 mg/m(2) IV weekly in cycle 1, then every 28 days) and gemcitabine (1000 mg/m(2) IV, days 1, 8 and 15, or days 1 and 15)...
February 2013: Leukemia & Lymphoma
David Telio, Kim Fernandes, Clement Ma, Richard Tsang, Armand Keating, Michael Crump, John Kuruvilla
Patients with primary refractory diffuse large B-cell lymphoma (REF DLBCL: progression on or within 3 months of completion of primary therapy) sensitive to salvage chemotherapy undergo autologous stem cell transplant (ASCT). We conducted a retrospective review of 111 patients with REF DLBCL treated between 1999 and 2007. Primary treatment consisted of cyclophosphamide, adriamycin, vincristine and prednisone (CHOP; 66%) and rituximab with CHOP (R-CHOP; 33%); 14% received involved field radiation. The response rate (RR) to first salvage chemotherapy was 23% (RR by regimen: dexamethasone, cytosine arabinoside and cisplatin [DHAP] 15%, etoposide, Solu-Medrol, cytosine arabinoside and cisplatin [ESHAP] 36%, and gemcitabine, dexamethasone and cisplatin [GDP] 45%); 25% (n = 28) of patients underwent ASCT...
May 2012: Leukemia & Lymphoma
Mourad Aribi, Naima Mesli, Nesrine Remla, Badr-Eddine Sari, Abdesselam Taleb, Hadj Touhami, Mohamed-Amine Bekadja, Zahia Zouaoui-Benhadji, Kamel Bouzid, Kaoual Meguenni
CONTEXT: Support for non-Hodgkin's lymphoma (NHL) with large cells that is refractory or relapsed after first-line chemotherapy poses a greater therapeutic problem with bone marrow transplant therapy or when old age is a contra-indication for high-dose chemotherapy, especially among developing countries such as Algeria. AIM: To show that the regimen, including gemcitabine, could be more effective in treating elderly patients with diffuse large B-cell lymphoma (DLBCL) in relapse / refractory, without complete remission, when compared with the ESHAP (etoposide, cisplatine, solumedrol, aracytine) regimen...
January 2010: Journal of Cancer Research and Therapeutics
Byeong-Bae Park, Won Seog Kim, Hyeon Seok Eom, Jin Seok Kim, Young Yiul Lee, Suk Joong Oh, Dae Ho Lee, Cheolwon Suh
BACKGROUND: We investigated response rates to and toxicities of gemcitabine, ifosfamide, dexamethasone, and oxaliplatin (GIDOX) for the treatment of relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: Patients with recurrent or refractory diffuse large B-cell lymphoma or mantle cell lymphoma (DLBCL) were eligible for enrollment in this study. Treatment consisted of gemcitabine 1,000 mg/m(2) intravenously (i.v.) on Days 1 and 8, ifosfamide 2,000 mg/m(2) i...
February 2011: Investigational New Drugs
Bhawna Sirohi, David Cunningham, Andy Norman, Kim Last, Ian Chau, Alan Horwich, Jacqui Oates, Geoffrey Chong, Andrew Wotherspoon
This is the first report of the combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) with Rituximab (GEM-PR) for diffuse large B-cell lymphoma (DLBCL). Thirty-nine patients with relapsed or refractory DLBCL in this study received GEM-P with (n = 24) or without Rituximab (n = 15) 64% patients had Stage III/IV disease. The overall response rate (ORR) was 59% (95% CI 42.1-74.4); 11/39 (28%) patients attained complete response. Patients received a median of two cycles (1-4) of treatment. For GEM-PR group, the ORR was 67% (95% CI 45-84%) compared to 47% (95% CI 21-73%) in GEM-P alone...
April 2007: Hematology (Amsterdam, Netherlands)
C Wenger, M Stern, R Herrmann, Ch Rochlitz, M Pless
The standard treatment for patients with aggressive B-cell lymphoma--particularly diffuse large-B-cell lymphoma [DLBCL)--is cyclophosphamide, doxorubicin, vincristine and prednisone [CHOP) plus rituximab, a chimeric monoclonal antibody against the CD20 antigen. However, some patients are not fit enough to tolerate CHOP or they relapse after previous therapy with CHOP. Gemcitabine as a monotherapy is active and relatively non-toxic in the treatment of NHL. We investigated the toxicity and efficacy of a combination of gemcitabine with rituximab in a small series of elderly patients with high-grade B-cell lymphoma who had either a relapse after CHOP, or were medically unfit to tolerate CHOP as a first-line therapy...
January 2005: Leukemia & Lymphoma
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