Desenlaces clínicos en hematoncología: diez años de investigaciones en Pubmed

Autores/as

  • Diego Rosselli Pontificia Universidad Javeriana
  • Carlos Eduardo Díaz Pontificia Universidad Javeriana
  • Laura Gutiérrez Pontificia Universidad Javeriana

Palabras clave:

Mieloma múltiple, Leucemias, Linfomas, Estudios clínicos aleatorizados;, Oncología, Desenlaces intermedios, Supervivencia global

Resumen

Objetivo: Determinar cuáles son los desenlaces clínicos empleados en los estudios fase III de tratamiento de neoplasias hematoncológicas y qué proporción de ellos emplean supervivencia global como desenlace primario.
Método: Mediante una búsqueda en Pubmed, analizar todos los experimentos clínicos aleatorios publicados en los últimos 10 años, de tratamientos de novo, en población adulta.
Resultados: La búsqueda inicial arrojó 310 referencias, entre las que se seleccionaron 90 estudios clínicos. La enfermedad más estudiada fue mieloma múltiple, con 29 estudios, seguida de linfoma no Hodgkin, con 26. Las otras fueron: leucemia mieloide aguda (12), leucemia linfocítica crónica (10), leucemia mieloide crónica (8), síndromes mielodisplásicos (3) y linfoma de Hodgkin (2). En 20 estudios (22%) se empleó la supervivencia global como desenlace primario (en solo 3 de ellos alcanzó significación estadística), en 37 más (41%) se agrupó con otros desenlaces para conformar un desenlace compuesto. En 55 estudios (61%) la supervivencia global fue un desenlace secundario.
Conclusiones: Aunque la supervivencia global es el estándar de oro en terapia oncológica, los desenlaces agrupados u otros, como tiempo libre de enfermedad o indicadores paraclínicos de actividad de la enfermedad, son más empleados, quizá por ser buenos predictores y requerir muestras y seguimientos menores. Su capacidad para predecir supervivencia global (en algunos casos calidad de vida) debe ser validada. Solo en las formas más agresivas de cáncer se justifica usar de rutina la supervivencia global como el desenlace primario.

Biografía del autor/a

Diego Rosselli, Pontificia Universidad Javeriana

Departamento de Epidemiología Clínica y Bioestadística, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá D.C., Colombia

Carlos Eduardo Díaz, Pontificia Universidad Javeriana

Departamento de Epidemiología Clínica y Bioestadística, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá D.C., Colombia

Laura Gutiérrez, Pontificia Universidad Javeriana

Departamento de Epidemiología Clínica y Bioestadística, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá D.C., Colombia

Referencias bibliográficas

Lee SJ, Earle CC, Weeks JC. Outcomes research in oncology: History, conceptual framework, and trends in the literature. J Natl Cancer Inst. 2000;92:195-204.

https://doi.org/10.1093/jnci/92.3.195

Jefford M, Stockler MR, Tattersall MHN. Outcomes research: What is it and why does it matter? Intern Med J. 2003;33:110-8.

Clancy CM, Eisenberg JM. Outcomes research: Measuring the end results of health care. Science. 1998;282:245-6.

https://doi.org/10.1126/science.282.5387.245

Temple R. Are surrogate markers adequate to assess cardiovascular disease drugs? JAMA. 1999;282:790-5.

https://doi.org/10.1001/jama.282.8.790

Karakiewicz PI, Briganti A, Chun FK-H, Valiquette L. Outcomes research: A methodologic review. Eur Urol. 2006;50:218-24.

https://doi.org/10.1016/j.eururo.2006.05.009

Lebwohl D, Kay A, Berg W, Baladi JF, Zheng J. Progressionfree survival: Gaining on overall survival as a gold standard and accelerating drug development. Cancer J. 2009;15: 386-94.

https://doi.org/10.1097/PPO.0b013e3181b9c5ec

Shi Q, Sargent DJ. Meta-analysis for the evaluation of surrogate endpoints in cancer clinical trials. Int J Clin Oncol. 2009;14:102-11.

https://doi.org/10.1007/s10147-009-0885-4

Kelloff GJ, Sigman CC, Johnson KM, Boone CW, Greenwald P, Crowell JA, et al. Perspectives on surrogate end points in the development of drugs that reduce the risk of cancer. Cancer Epidemiol Biomarkers Prev. 2000;9:127-37.

Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:89-95.

https://doi.org/10.1067/mcp.2001.113989

Vanderweele TJ. Surrogate measures and consistent surrogates. Biometrics. 2013;69:561-9.

https://doi.org/10.1111/biom.12071

Driscoll JJ, Rixe O. Overall survival: Still the gold standard: Why overall survival remains the definitive end point in cancer clinical trials. Cancer J. 2009;15:401-5.

https://doi.org/10.1097/PPO.0b013e3181bdc2e0

Knauf WU, Lissitchkov T, Aldaoud A, Liberati AM, Loscertales J, Herbrecht R, et al. Bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukaemia: updated results of a randomized phase III trial. Br J Haematol. 2012;159:67-77.

https://doi.org/10.1111/bjh.12000

Lepretre S, Aurran T, Mahé B, Cazin B, Tournilhac O, Maisonneuve H, et al. Excess mortality after treatment with fludarabine and cyclophosphamide in combination with alemtuzumab in previously untreated patients with chronic lymphocytic leukemia in a randomized phase 3 trial. Blood. 2012;119:5104-10.

https://doi.org/10.1182/blood-2011-07-365437

Reynolds C, di Bella N, Lyons RM, Hyman W, Richards DA, Robbins GJ, et al. A phase III trial of fludarabine, cyclophosphamide, and rituximab vs pentostatin, cyclophosphamide, and rituximab in B-cell chronic lymphocytic leukemia. Invest New Drugs. 2012;30:1232-40.

https://doi.org/10.1007/s10637-011-9737-y

Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: A randomised, open-label, phase 3 trial. Lancet. 2010;376:1164-74.

https://doi.org/10.1016/S0140-6736(10)61381-5

Robak T, Jamroziak K, Gora-Tybor J, Stella-Holowiecka B, Konopka L, Ceglarek B, et al. Comparison of cladribine plus cyclophosphamide with fludarabine plus cyclophosphamide as first-line therapy for chronic lymphocytic leukemia: A phase III randomized study by the Polish Adult Leukemia Group (PALGCLL3 Study). J Clin Oncol. 2010;28:1863-9.

https://doi.org/10.1200/JCO.2009.25.9630

Knauf WU, Lissichkov T, Aldaoud A, Liberati A, Loscertales J, Herbrecht R, et al. Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol. 2009;27:4378-84.

https://doi.org/10.1200/JCO.2008.20.8389

Eichhorst BF, Busch R, Stilgenbauer S, Stauch M, Bergmann MA, Ritgen M, et al. First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia. Blood. 2009;114:3382-91.

https://doi.org/10.1182/blood-2009-02-206185

Hillmen P, Skotnicki AB, Robak T, Jaksic B, Dmoszynska A, Wu J, et al. Alemtuzumab compared with chlorambucil as firstline therapy for chronic lymphocytic leukemia. J Clin Oncol. 2007;25:5616-23.

https://doi.org/10.1200/JCO.2007.12.9098

Flinn IW, Neuberg DS, Grever MR, Dewald GW, Bennett JM, Paietta EM, et al. Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997. J Clin Oncol. 2007;25:793-8.

https://doi.org/10.1200/JCO.2006.08.0762

Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Lacobelli S, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369:111-21.

https://doi.org/10.1056/NEJMoa1300874

Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, et al. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013;121:4854-60.

https://doi.org/10.1182/blood-2013-01-466706

Kantarjian HM, Thomas XG, Dmoszynska A, Wierzbowska A, Mazur G, Mayer J, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012;30:2670-7.

https://doi.org/10.1200/JCO.2011.38.9429

Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, et al. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: A multicenter, randomized phase III study. J Clin Oncol. 2012;30:2441-8.

https://doi.org/10.1200/JCO.2011.37.1286

Hengeveld M, Suciu S, Karrasch M, Specchia G, Marie JP, Muus P, et al. Intensive consolidation therapy compared with standard consolidation and maintenance therapy for adults with acute myeloid leukaemia aged between 46 and 60 years: Final results of the randomized phase III study (AML 8B) of the European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups. Ann Hematol. 2012;91:825-35.

https://doi.org/10.1007/s00277-012-1436-z

Brune M, Castaigne S, Catalano J, Gehlsen K, Ho AD, Hofmann WK, et al. Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: Results of a randomized phase 3 trial. Blood. 2006;108:88-96.

https://doi.org/10.1182/blood-2005-10-4073

Harousseau J-L, Martinelli G, Jedrzejczak WW, Brandwein JM, Bordessoule D, Masszi T, et al. A randomized phase 3 study of tipifarnib compared with best supportive care, including hydroxyurea, in the treatment of newly diagnosed acute myeloid leukemia in patients 70 years or older. Blood. 2009;114:1166-73.

https://doi.org/10.1182/blood-2009-01-198093

Latagliata R, Breccia M, Fazi P, Lacobelli S, Martinelli G, di Raimondo F, et al. Liposomal daunorubicin versus standard daunorubicin: Long term follow-up of the GIMEMA GSI 103 AMLE randomized trial in patients older than 60 years with acute myelogenous leukaemia. Br J Haematol. 2008;143:681-9.

https://doi.org/10.1111/j.1365-2141.2008.07400.x

Russo D, Malagola M, de Vivo A, Fiacchini M, Martinelli G, Piccaluga PP, et al. Multicentre phase III trial on fludarabine, cytarabine (Ara-C), and idarubicin versus idarubicin, Ara-C and etoposide for induction treatment of younger, newly diagnosed acute myeloid leukaemia patients. Br J Haematol. 2005;131:172-9.

https://doi.org/10.1111/j.1365-2141.2005.05745.x

Schlenk RF, Fröhling S, Hartmann F, Fischer JT, Glasmacher A, del Valle F, et al. Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia. Leukemia. 2004;18:1798-803.

https://doi.org/10.1038/sj.leu.2403528

Amadori S, Suciu S, Jehn U, Stasi R, Thomas X, Marie JP, et al. Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: Final results of AML-13, a randomized phase-3 study. Blood. 2005;106:27-34.

https://doi.org/10.1182/blood-2004-09-3728

Cortes JE, Kim DW, Kantarjian HM, Brümmendorf TH, Dyagil I, Griskevicius L, et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: Results from the BELA trial. J Clin Oncol. 2012;30:3486-92.

https://doi.org/10.1200/JCO.2011.38.7522

Petzer AL, Fong D, Lion T, Dyagil I, Masliak Z, Bogdanovic A, et al. High-dose imatinib induction followed by standard-dose maintenance in pre-treated chronic phase chronic myeloid leukemia patients-final analysis of a randomized, multicenter, phase III trial. Haematologica. 2012;97:1562-9.

https://doi.org/10.3324/haematol.2011.060087

Kantarjian HM, Shah NP, Cortes JE, Baccarani M, Agarwal MB, Undurraga MS, et al. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2012;119:1123-9.

https://doi.org/10.1182/blood-2011-08-376087

Kantarjian HM, Hochhaus A, Saglio G, de Souza C, Flinn IW, Stenke L, et al. Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. Lancet Oncol. 2011;12:841-51.

https://doi.org/10.1016/S1470-2045(11)70201-7

Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362:2260-70.

https://doi.org/10.1056/NEJMoa1002315

Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362:2251-9.

https://doi.org/10.1056/NEJMoa0912614

Cortes JE, Baccarani M, Guilhot F, Druker BJ, Branford S, Kim DW, et al. Phase III, randomized, open-label study of daily imatinib mesylate 400 mg versus 800 mg in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase using molecular end points: Tyrosine kinase inhibitor optimization and selectivity study. J Clin Oncol. 2010;28:424-30.

https://doi.org/10.1200/JCO.2009.25.3724

Deenik W, van der Holt B, Verhoef GE, Schattenberg AV, Verdonck LF, Daenen SM, et al. High-vs low-dose cytarabine combined with interferon alfa in patients with first chronic phase chronic myeloid leukemia. A prospective randomized phase III study. Ann Hematol. 2007;86:117-25.

https://doi.org/10.1007/s00277-006-0186-1

Gordon LI, Hong F, Fisher RI, Bartlett NL, Connors JM, Gascoyne RD, et al. Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced-stage Hodgkin lymphoma: An intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol. 2013;31:684-91.

https://doi.org/10.1200/JCO.2012.43.4803

Engert A, Haverkamp H, Kobe C, Markova J, Renner C, Ho A, et al. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): A randomised, open-label, phase 3 non-inferiority trial. Lancet. 2012;379:1791-9.

https://doi.org/10.1016/S0140-6736(11)61940-5

Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, et al. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): An open-label randomised phase 3 trial. Lancet. 2011;378:1858-67.

https://doi.org/10.1016/S0140-6736(11)61040-4

Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): A phase 3, randomised controlled trial. Lancet. 2011;377:42-51.

https://doi.org/10.1016/S0140-6736(10)62175-7

Marcus R, Imrie K, Solal-Celigny P, Catalano JV, Dmoszynska A, Raposo JC, et al. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol. 2008;26:4579-86.

https://doi.org/10.1200/JCO.2007.13.5376

Herold M, Haas A, Srock S, Neser S, Al-Ali KH, Neubauer A, et al. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: An East German Study Group Hematology and Oncology Study. J Clin Oncol. 2007;25:1986-92.

https://doi.org/10.1200/JCO.2006.06.4618

Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: Results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005;106:3725-32.

https://doi.org/10.1182/blood-2005-01-0016

Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, et al. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: A phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013;381:1817-26.

https://doi.org/10.1016/S0140-6736(13)60313-X

Delarue R, Tilly H, Mounier N, Petrella T, Salles G, Thieblemont C, et al. Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): A randomised phase 3 trial. Lancet Oncol. 2013;14:525-33.

https://doi.org/10.1016/S1470-2045(13)70122-0

Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, et al. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: An open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013;381:1203-10.

https://doi.org/10.1016/S0140-6736(12)61763-2

Zucca E, Conconi A, Laszlo D, López-Guillermo A, Bouabdallah R, Coiffier B, et al. Addition of rituximab to chlorambucil produces superior event-free survival in the treatment of patients with extranodal marginal-zone B-cell lymphoma: 5 year analysis of the IELSG-19 Randomized Study. J Clin Oncol. 2013;31:565-72.

https://doi.org/10.1200/JCO.2011.40.6272

Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, et al. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013;24:1032-7.

https://doi.org/10.1093/annonc/mds600

Press OW, Unger JM, Rimsza LM, Friedberg JW, LeBlanc M, Czuczman MS, et al. Phase III randomized intergroup trial of CHOP plus rituximab compared with CHOP chemotherapy plus (131)iodine-tositumomab for previously untreated follicular non-Hodgkin lymphoma: SWOG S0016. J Clin Oncol. 2013;31:314-20.

https://doi.org/10.1200/JCO.2012.42.4101

Schmitz N, Nickelsen M, Ziepert M, Haenel M, Borchmann P, Schmidt C, et al. Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: An open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol. 2012;13:1250-9.

https://doi.org/10.1016/S1470-2045(12)70481-3

Economopoulos T, Psyrri A, Dimopoulos MA, Kalogera-Fountzila A, Pavlidis N, Tsatalas C, et al. CEOP-21 versus CEOP-14 chemotherapy with or without rituximab for the first-line treatment of patients with aggressive lymphomas: Results of the HE22A99 trial of the Hellenic Cooperative Oncology Group. Cancer J. 2007;13:327-34.

https://doi.org/10.1097/PPO.0b013e3181570170

Watanabe T, Tobinai K, Shibata T, Tsukasaki K, Morishima Y, Maseki N, et al. Phase II/III study of R-CHOP-21 versus R-CHOP 14 for untreated indolent B-cell non-Hodgkin's lymphoma: JCOG 0203 trial. J Clin Oncol. 2011;29:3990-8.

https://doi.org/10.1200/JCO.2011.34.8508

Lowry L, Smith P, Qian W, Falk S, Benstead K, Illidge T, et al. Reduced dose radiotherapy for local control in non-Hodgkin lymphoma: A randomised phase III trial. Radiother Oncol. 2011;100:86-92.

https://doi.org/10.1016/j.radonc.2011.05.013

Tsukasaki K, Utsunomiya A, Fukuda H, Shibata T, Fukushima T, Takatsuka Y, et al. VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study JCOG9801. J Clin Oncol. 2007;25:5458-64.

https://doi.org/10.1200/JCO.2007.11.9958

Ohmachi K, Tobinai K, Kobayashi Y, Itoh K, Nakata M, Shibata T, et al. Phase III trial of CHOP-21 versus CHOP-14 for aggressive non-Hodgkin's lymphoma: Final results of the Japan Clinical Oncology Group Study, JCOG 9809. Ann Oncol. 2011;22:1382-91.

https://doi.org/10.1093/annonc/mdq619

Fridrik MA, Hausmaninger H, Lang A, Drach J, Krieger O, Geissler D, et al. Dose-dense therapy improves survival in aggressive non-Hodgkin's lymphoma. Ann Hematol. 2010;89:273-82.

https://doi.org/10.1007/s00277-009-0811-x

Avilés A, Castañeda C, Neri N, Cleto S, Talavera A, González M, et al. Results of a phase III clinical trial: CHOP versus CMED in peripheral T-cell lymphoma unspecified. Med Oncol. 2008;25:360-4.

Merli F, Bertini M, Luminari S, Mozzana R, Botto B, Liberati AM, et al. Long term results of a randomized study performed by Intergruppo Italiano Linfomi comparing Mini-CEOP vs P-VEBEC in elderly patients with diffuse large B-cell lymphoma. Leuk Lymphoma. 2007;48:367-73.

https://doi.org/10.1080/10428190601078100

Verdonck LF, Notenboom A, de Jong DD, MacKenzie MA, Verhoef GE, Kramer MH, et al. Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: A phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON). Blood. 2007;109:2759-66.

https://doi.org/10.1182/blood-2006-07-035709

Betticher DC, Martinelli G, Radford JA, Kaufmann M, Dyer MJ, Kaiser U, et al. Sequential high dose chemotherapy as initial treatment for aggressive sub-types of non-Hodgkin lymphoma: Results of the international randomized phase III trial (MISTRAL). Ann Oncol. 2006;17:1546-52.

https://doi.org/10.1093/annonc/mdl153

Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006;24:3121-7.

https://doi.org/10.1200/JCO.2005.05.1003

Hagenbeek A, Eghbali H, Monfardini S, Vitolo U, Hoskin PJ, de Wolf-Peeters C, et al. Phase III intergroup study of fludarabine phosphate compared with cyclophosphamide, vincristine, and prednisone chemotherapy in newly diagnosed patients with stage III and IV low-grade malignant Non-Hodgkin's lymphoma. J Clin Oncol. 2006;24:1590-6.

https://doi.org/10.1200/JCO.2005.03.7952

Burton C, Linch D, Hoskin P, Milligan D, Dyer MJ, Hancock B, et al. A phase III trialcomparing CHOP to PMitCEBO with or without G-CSF in patients aged 60 plus with aggressive non- Hodgkin's lymphoma. Br J Cancer. 2006;94:806-13.

https://doi.org/10.1038/sj.bjc.6602975

Federico M, Luminari S, Gobbi PG, Sacchi S, di Renzo N, Lombardo M, et al. The length of treatment of aggressive non-Hodgkin's lymphomas established according to the international prognostic index score: Long-term results of the GISL LA03 study. Eur J Haematol. 2006;76:217-29.

https://doi.org/10.1111/j.1600-0609.2005.00609.x

Chamorey E, Gressin R, Peyrade F, Rossi JF, Lepeu G, Foussard C, et al. Prospective randomized study comparing MEMID with a chop-like regimen in elderly patients with aggressive nonHodgkin's lymphoma. Oncology. 2005;69:19-26.

https://doi.org/10.1159/000087284

Foussard C, Colombat P, Maisonneuve H, Berthou C, Gressin R, Rousselet MC, et al. 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, lowgrade non-Hodgkin's lymphoma before the era of. Ann Oncol. 2005;16:466-72.

https://doi.org/10.1093/annonc/mdi091

Mateos MV, Hernández MT, Giraldo P, de la Rubia J, de Arriba F, López Corral L, et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med. 2013;369:438-47.

https://doi.org/10.1056/NEJMoa1300439

Mellqvist UH, Gimsing P, Hjertner O, Lenhoff S, Laane E, Remes K, et al. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: A Nordic Myeloma Study Group randomized phase 3 trial. Blood. 2013;121:4647-54.

https://doi.org/10.1182/blood-2012-11-464503

Stewart AK, Trudel S, Bahlis NJ, White D, Sabry W, Belch A, et al. A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: The National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial. Blood. 2013;121:1517-23.

https://doi.org/10.1182/blood-2012-09-451872

Witzig TE, Laumann KM, Lacy MQ, Hayman SR, Dispenzieri A, Kumar S, et al. A phase III randomized trial of thalidomide plus zoledronic acid versus zoledronic acid alone in patients with asymptomatic multiple myeloma. Leukemia. 2013;27:220-5.

https://doi.org/10.1038/leu.2012.236

Sonneveld P, Schmidt-Wolf IGH, van der Holt B, El Jarari L, Bertsch U, Salwender H, et al. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: Results of the randomized phase III HOVON65/GMMG-HD4 trial. J Clin Oncol. 2012;30:2946-55.

https://doi.org/10.1200/JCO.2011.39.6820

Rosiñol L, Oriol A, Teruel AI, Hernández D, López-Jiménez J, de la Rubia J, et al. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: A randomized phase 3 PETHEMA/GEM study. Blood. 2012;120:1589-96.

https://doi.org/10.1182/blood-2012-02-408922

Garderet L, Lacobelli S, Moreau P, Dib M, Lafon I, Nieder- wieser D, et al. Superiority of the triple combination of bortezomib-thalidomide-dexamethasone over the dual combination of thalidomide-dexamethasone in patients with multiple myeloma progressing or relapsing after autologous transplantation: The MMVAR/IFM 2005-04 Randomized Phase III Trial from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2012;30:2475-82.

https://doi.org/10.1200/JCO.2011.37.4918

Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366: 1782-91.

https://doi.org/10.1056/NEJMoa1114138

McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366: 1770-81.

https://doi.org/10.1056/NEJMoa1114083

Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, et al. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012;366:1759-69.

https://doi.org/10.1056/NEJMoa1112704

Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, et al. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2012;120:9-19.

https://doi.org/10.1182/blood-2012-02-408898

Morabito F, Gentile M, Mazzone C, Rossi D, di Raimondo F, Bringhen S, et al. Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment. Blood. 2011;118: 5759-66.

https://doi.org/10.1182/blood-2011-05-353995

Spicka I, Mateos MV, Redman K, Dimopoulos MA, Richardson PG. An overview of the VISTA trial: Newly diagnosed, untreated patients with multiple myeloma ineligible for stem cell transplantation. Immunotherapy. 2011;3:1033-40.

https://doi.org/10.2217/imt.11.104

Morgan GJ, Davies FE, Gregory WM, Russell NH, Bell SE, Szubert AJ, et al. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood. 2011;118:1231-8.

https://doi.org/10.1182/blood-2011-02-338665

Palumbo A, Bringhen S, Rossi D, Cavalli M, Larocca A, Ria R, et al. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol. 2010;28:5101-9.

https://doi.org/10.1200/JCO.2010.29.8216

Wijermans P, Schaafsma M, Termorshuizen F, Ammerlaan R, Wittebol S, Sinnige H, et al. Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: The HOVON 49 Study. J Clin Oncol. 2010;28:3160-6.

https://doi.org/10.1200/JCO.2009.26.1610

Waage A, Gimsing P, Fayers P, Abildgaard N, Ahlberg L, Björkstrand B, et al. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood. 2010;116:1405-12.

https://doi.org/10.1182/blood-2009-08-237974

Nair B, van Rhee F, Shaughnessy JD, Anaissie E, Szymonifka J, Hoering A, et al. Superior results of Total Therapy 3 (2003-33) in gene expression profiling-defined low-risk multiple myeloma confirmed in subsequent trial 2006-66 with VRD maintenance. Blood. 2010;115:4168-73.

Palumbo A, Bringhen S, Bruno B, Falcone AP, Liberati AM, Grasso M, et al. Melphalan 200mg/m2 versus melphalan 100 mg/m2 in newly diagnosed myeloma patients: A prospective, multicenter phase 3 study. Blood. 2010;115:1873-9.

https://doi.org/10.1182/blood-2009-09-241737

Dimopoulos MA, Richardson PG, Schlag R, Khuageva NK, Shpilberg O, Kastritis E, et al. VMP (Bortezomib, Melphalan, and Prednisone) is active and well tolerated in newly diagnosed patients with multiple myeloma with moderately impaired renal function, and results in reversal of renal impairment: Cohort analysis of the phase III VISTA study. J Clin Oncol. 2009;27:6086-93.

https://doi.org/10.1200/JCO.2009.22.2232

Hulin C, Facon T, Rodon P, Pegourie B, Benboubker L, Doyen C, et al. Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial. J Clin Oncol. 2009;27:3664-70.

https://doi.org/10.1200/JCO.2008.21.0948

Kyle RA, Jacobus S, Friedenberg WR, Slabber CF, Rajkumar SV, Greipp PR. The treatment of multiple myeloma using vincristine, carmustine, melphalan, cyclophosphamide, and prednisone (VBMCP) alternating with high-dose cyclophosphamide and alpha(2)beta interferon versus VBMCP: results of a phase III Eastern Cooperative Oncology Study E5A93. Cancer. 2009;115:2155-64.

https://doi.org/10.1002/cncr.24221

San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpil- berg O, Kropff M, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008;359:906-17.

https://doi.org/10.1056/NEJMoa0801479

Rajkumar SV, Rosin ̃ol L, Hussein M, Catalano J, Jedrzejczak W, Lucy L, et al. Multicenter, randomized, double-blind, placebocontrolled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol. 2008;26:2171-7.

https://doi.org/10.1200/JCO.2007.14.1853

Barlogie B, Tricot G, Anaissie E, Shaughnessy J, Rasmussen E, van Rhee F, et al. Thalidomide and hematopoieticcell transplantation for multiple myeloma. N Engl J Med. 2006;354:1021-30.

https://doi.org/10.1056/NEJMoa053583

Barlogie B, Kyle RA, Anderson KC, Greipp PR, Lazarus HM, Hurd DD, et al. Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup Trial S9321. J Clin Oncol. 2006;24:929-36.

https://doi.org/10.1200/JCO.2005.04.5807

Rifkin RM, Gregory SA, Mohrbacher A, Hussein MA. Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma: A phase III multicenter randomized trial. Cancer. 2006;106:848-58.

https://doi.org/10.1002/cncr.21662

Pönisch W, Mitrou PS, Merkle K, Herold M, Assmann M, Wilhelm G, et al. Treatment of bendamustine and prednisone in patients with newly diagnosed multiple myeloma results in superior complete response rate, prolonged time to treatment failure and improved quality of life compared to treatment with melphalan and prednisone-a randomized phase III study of the East German Study Group of Hematology and Oncology (OSHO). J Cancer Res Clin Oncol. 2006;132: 205-12.

https://doi.org/10.1007/s00432-005-0074-4

Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: A clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol. 2006;24:431-6.

https://doi.org/10.1200/JCO.2005.03.0221

Kantarjian H, Issa JP, Rosenfeld CS, Bennett JM, Albitar M, DiPersio J, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: Results of a phase III randomized study. Cancer. 2006;106:1794-803.

https://doi.org/10.1002/cncr.21792

Zwierzina H, Suciu S, Loeffler-Ragg J, Neuwirtova R, Fenaux P, Beksac M, et al. Low-dose cytosine arabinoside (LD-AraC) vs LD-AraC plus granulocyte/macrophage colony stimulating factor vs LD-AraC plus Interleukin-3 for myelodysplastic syndrome patients with a high risk of developing acute leukemia: Final results of a randomized phase. Leukemia. 2005;19:1929-33.

https://doi.org/10.1038/sj.leu.2403934

Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med. 2012;367:1487-96.

https://doi.org/10.1056/NEJMoa1203517

Pazdur R. Endpoints for assessing drug activity in clinical trials. Oncologist. 2008;13 Suppl 2:19-21.

https://doi.org/10.1634/theoncologist.13-S2-19

Sargent DJ, Wieand HS, Haller DG, Gray R, Benedetti JK, Buyse M, et al. Disease-free survival versus overall survival as a primary end point for adjuvant colon cancer studies: individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol. 2005;23:8664-70.

https://doi.org/10.1200/JCO.2005.01.6071

Piedbois P, Buyse M. Endpoints and surrogate endpoints in colorectal cancer: A review of recent developments. Curr Opin Oncol. 2008;20:466-71.

https://doi.org/10.1097/CCO.0b013e32830218fe

Saad ED, Katz A, Buyse M. Overall survival and post-progression survival in advanced breast cancer: A review of recent randomized clinical trials. J Clin Oncol. 2010;28:1958-62.

https://doi.org/10.1200/JCO.2009.25.5414

Cómo citar

[1]
Rosselli, D. , Díaz C.E. y Gutiérrez L. 2015. Desenlaces clínicos en hematoncología: diez años de investigaciones en Pubmed. Revista Colombiana de Cancerología. 19, 2 (jun. 2015), 95–102.

Descargas

Los datos de descargas todavía no están disponibles.

Descargas

Publicado

2015-06-01

Número

Sección

Artículos de revisión