Summary
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/m2 intravenously (i.v.) on Days 1 and 8, ifosfamide 2,000 mg/m2 i.v. on Day 1, dexamethasone 40 mg orally on Days 1–4, and oxaliplatin 130 mg/m2 i.v. on Day 2, every 21 days. The primary goal of treatment was to establish a response rate after three cycles. Afterwards, patients could proceed to high-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) or receive up to six treatment cycles. Results: Twenty-seven eligible patients were evaluated for toxicity and response. The median age of the patients was 54 years (range, 18–75 years), and most had DLBCL. After three cycles, there were four CR (15%) and 10 PR (37%) for an overall response rate (RR) of 52%. Among a total of 88 GIDOX cycles, grade 3 and 4 neutropenia occurred in 33% and 16% of the cycles, respectively. Likewise, grade 3 and 4 thrombocytopenia occurred in 14% and 16% of the cycles, respectively. Two patients (2%) experienced febrile neutropenia, while seven patients (26%) proceeded to HDC-ASCT. Conclusions: GIDOX is an active salvage regimen for aggressive B-cell NHL and can be tolerated by patients with acceptable toxicity.
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Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL et al (1995) Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med 333:1540–1545
Mills W, Chopra R, McMillan A, Pearce R, Linch DC, Goldstone AH (1995) BEAM chemotherapy and autologous bone marrow transplantation for patients with relapsed or refractory non-Hodgkin's lymphoma. J Clin Oncol 13:588–595
Schutt P, Passon J, Ebeling P, Welt A, Muller S, Metz K, Moritz T, Seeber S, Nowrousian MR (2007) Ifosfamide, etoposide, cytarabine, and dexamethasone as salvage treatment followed by high-dose cyclophosphamide, melphalan, and etoposide with autologous peripheral blood stem cell transplantation for relapsed or refractory lymphomas. Eur J Haematol 78:93–101
Wheeler C, Strawderman M, Ayash L, Churchill WH, Bierer BE, Elias A, Gilliland DG, Antman K, Guinan EC, Eder JP et al (1993) Prognostic factors for treatment outcome in autotransplantation of intermediate-grade and high-grade non-Hodgkin's lymphoma with cyclophosphamide, carmustine, and etoposide. J Clin Oncol 11:1085–1091
Aviles A, Neri N, Huerta-Guzman J, Fernandez R (2004) Gemcitabine and cisplatin in refractory malignant lymphoma. Oncology 66:197–200
Crump M, Baetz T, Couban S, Belch A, Marcellus D, Howson-Jan K, Imrie K, Myers R, Adams G, Ding K, Paul N, Shepherd L, Iglesias J, Meyer R (2004) Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology B-cell non-Hodgkin lymphoma: a Phase II study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). Cancer 101:1835–1842
Ng M, Waters J, Cunningham D, Chau I, Horwich A, Hill M, Norman AR, Wotherspoon A, Catovsky D (2005) Gemcitabine, cisplatin and methylprednisolone (GEM-P) is an effective salvage regimen in patients with relapsed and refractory lymphoma. Br J Cancer 92:1352–1357
Hanel M, Kroger N, Hoffknecht MM, Peters SO, Metzner B, Fiedler F, Braumann D, Schubert JC, Illiger HJ, Hanel A, Kruger WH, Zeller W, Weh HJ, Hossfeld DK, Zander AR (2000) ASHAP–an effective salvage therapy for recurrent and refractory malignant lymphomas. Ann Hematol 79:304–311
Velasquez WS, Cabanillas F, Salvador P, McLaughlin P, Fridrik M, Tucker S, Jagannath S, Hagemeister FB, Redman JR, Swan F et al (1988) Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood 71:117–122
Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F (1994) ESHAP–an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol 12:1169–1176
Hagemeister FB (1999) The role of ifosfamide in the treatment of lymphomas. Leuk lymphoma 34:433–441
Moskowitz CH, Bertino JR, Glassman JR, Hedrick EE, Hunte S, Coady-Lyons N, Agus DB, Goy A, Jurcic J, Noy A, O'Brien J, Portlock CS, Straus DS, Childs B, Frank R, Yahalom J, Filippa D, Louie D, Nimer SD, Zelenetz AD (1999) Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma. J Clin Oncol 17:3776–3785
Corazzelli G, Russo F, Capobianco G, Marcacci G, Della Cioppa P, Pinto A (2006) Gemcitabine, ifosfamide, oxaliplatin and rituximab (R-GIFOX), a new effective cytoreductive/mobilizing salvage regimen for relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a pilot study. Ann Oncol Suppl 4:iv18–24
Goldin A (1982) Ifosfamide in experimental tumor systems. Semin Oncol 9:14–23
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V (2007) Revised response criteria for malignant lymphoma. J Clin Oncol 25:579–586
Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10:1–10
Millikan RE, Plunkett WK, Smith TL, Williams DL, Logothetis CJ (2001) Gemcitabine modulation of alkylator therapy: a phase I trial of escalating gemcitabine added to fixed doses of ifosfamide and doxorubicin. Cancer 92:194–199
Papageorgiou ES, Tsirigotis P, Dimopoulos M, Pavlidis N, Fountzilas G, Papageorgiou S, Economopoulos T (2005) Combination chemotherapy with gemcitabine and vinorelbine in the treatment of relapsed or refractory diffuse large B-cell lymphoma: a phase-II trial by the Hellenic Cooperative Oncology Group. Eur J Haematol 75:124–129
Aurer I, Durakovic N, Radman I, Nemet D, Zupancic-Salek S, Kovacevic-Metelko J, Bogdanic V, Sertic D, Mrsic M, Mikulic M, Labar B (2002) Combination of ifosfamide, methotrexate, and etoposide (IMVP) as a salvage therapy for relapsed and refractory aggressive non-Hodgkin lymphoma: retrospective study. Croat Med J 43:550–554
Rodriguez MA, Cabanillas FC, Velasquez W, Hagemeister FB, McLaughlin P, Swan F, Romaguera JE (1995) Results of a salvage treatment program for relapsing lymphoma: MINE consolidated with ESHAP. J Clin Oncol 13:1734–1741
Santoro A, Magagnoli M, Spina M, Pinotti G, Siracusano L, Michieli M, Nozza A, Sarina B, Morenghi E, Castagna L, Tirelli U, Balzarotti M (2007) Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin's lymphoma. Haematologica 92:35–41
Recchia F, De Filippis S, Rosselli M, Pompili P, Guerriero G, Rea S (1999) Ifosfamide, vinorelbine and gemcitabine in advanced non-small cell lung cancer. A phase I study. Eur J Cancer 35:1457–1461
Sirohi B, Cunningham D, Norman A, Last K, Chau I, Horwich A, Oates J, Chong G, Wotherspoon A (2007) Gemcitabine, cisplatin and methylprednisolone (GEM-P) with or without Rituximab in relapsed and refractory patients with diffuse large B cell lymphoma (DLBCL). Hematology (Amsterdam, Netherlands) 12:149–153
Corazzelli G, Capobianco G, Arcamone M, Ballerini PF, Iannitto E, Russo F, Frigeri F, Becchimanzi C, Marcacci G, De Chiara A, Pinto A (2009) Long-term results of gemcitabine plus oxaliplatin with and without rituximab as salvage treatment for transplant-ineligible patients with refractory/relapsing B-cell lymphoma. Cancer chemother pharmacol
Hoster E, Dreyling M, Klapper W, Gisselbrecht C, van Hoof A, Kluin-Nelemans HC, Pfreundschuh M, Reiser M, Metzner B, Einsele H, Peter N, Jung W, Wormann B, Ludwig WD, Duhrsen U, Eimermacher H, Wandt H, Hasford J, Hiddemann W, Unterhalt M (2008) A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood 111:558–565
El Gnaoui T, Dupuis J, Belhadj K, Jais JP, Rahmouni A, Copie-Bergman C, Gaillard I, Divine M, Tabah-Fisch I, Reyes F, Haioun C (2007) Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy. Ann Oncol 18:1363–1368
Di Renzo N, Brugiatelli M, Montanini A, Vigliotti ML, Cervetti G, Liberati AM, Luminari S, Spedini P, Giglio G, Federico M (2006) Vinorelbine, gemcitabine, procarbazine and prednisone (ViGePP) as salvage therapy in relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL): results of a phase II study conducted by the Gruppo Italiano per lo Studio dei Linfomi. Leuk lymphoma 47:473–479
Morschhauser F, Depil S, Jourdan E, Wetterwald M, Bouabdallah R, Marit G, Solal-Celigny P, Sebban C, Coiffier B, Chouaki N, Bauters F, Dumontet C (2007) Phase II study of gemcitabine-dexamethasone with or without cisplatin in relapsed or refractory mantle cell lymphoma. Ann Oncol 18:370–375
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Park, BB., Kim, W.S., Eom, H.S. et al. Salvage therapy with gemcitabine, ifosfamide, dexamethasone, and oxaliplatin (GIDOX) for B-cell non-Hodgkin’s lymphoma: a consortium for improving survival of lymphoma (CISL) trial. Invest New Drugs 29, 154–160 (2011). https://doi.org/10.1007/s10637-009-9320-y
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DOI: https://doi.org/10.1007/s10637-009-9320-y