Sorafenib in Combination With Capecitabine: An Oral Regimen for Patients With HER2-Negative Locally Advanced or Metastatic Breast Cancer

Imagem de Miniatura
Arquivos
art_HOFF_Sorafenib_in_Combination_With_Capecitabine_An_Oral_Regimen_2012.PDF (177.27 KB)
Citações na Scopus
156
Tipo de produção
article
Data de publicação
2012
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
AMER SOC CLINICAL ONCOLOGY
Autores
BASELGA, Jose
SEGALLA, Jose Getulio Martins
ROCHE, Henri
GIGLIO, Auro del
PINCZOWSKI, Helio
CIRUELOS, Eva M.
CABRAL FILHO, Sebastiao
GOMEZ, Patricia
EYLL, Brigitte Van
BERMEJO, Begona
Citação
JOURNAL OF CLINICAL ONCOLOGY, v.30, n.13, p.1484-1491, 2012
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Purpose Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. A randomized, double-blind, placebo-controlled phase IIB trial assessed sorafenib with capecitabine for locally advanced or metastatic human epidermal growth factor receptor 2 (HER2) -negative breast cancer. Patients and Methods Patients were randomly assigned to first-or second-line capecitabine 1,000 mg/m(2) orally twice a day for days 1 to 14 of every 21-day cycle with sorafenib 400 mg orally twice a day or placebo. The primary end point was progression-free survival (PFS). Results In total, 229 patients were enrolled. The addition of sorafenib to capecitabine resulted in a significant improvement in PFS versus placebo (median, 6.4 v 4.1 months; hazard ratio [HR], 0.58; 95% CI, 0.41 to 0.81; P = .001) with sorafenib favored across subgroups, including first-line (HR, 0.50; 95% CI, 0.30 to 0.82) and second-line (HR, 0.65; 95% CI, 0.41 to 1.04) treatment. There was no significant improvement for overall survival (median, 22.2 v 20.9 months; HR, 0.86; 95% CI, 0.61 to 1.23; P = .42) and overall response (38% v 31%; P = .25). Toxicities (sorafenib v placebo) of any grade included rash (22% v 8%), diarrhea (58% v 30%), mucosal inflammation (33% v 21%), neutropenia (13% v 4%), hypertension (18% v 12%), and hand-foot skin reaction/hand-foot syndrome (HFSR/HFS; 90% v 66%); grade 3 to 4 toxicities were comparable between treatment arms except HFSR/HFS (44% v 14%). Reasons for discontinuation in the sorafenib and placebo arms included disease progression (63% v 82%, respectively), adverse events (20% v 9%, respectively), and death (0% v 1%, respectively). Conclusion Addition of sorafenib to capecitabine improved PFS in patients with HER2-negative advanced breast cancer. The dose of sorafenib used in this trial resulted in unacceptable toxicity for many patients. A phase III confirmatory trial has been initiated with a reduced sorafenib dose.
Palavras-chave
URI
https://observatorio.fm.usp.br/handle/OPI/1421
Referências
  1. Awada A, 2007, ANN ONCOL, V18, P39
  2. Banerjee S, 2007, NAT CLIN PRACT ONCOL, V4, P536, DOI 10.1038/ncponc0905
  3. Barrios CH, 2010, BREAST CANCER RES TR, V121, P121, DOI 10.1007/s10549-010-0788-0
  4. Bergh J, 2010, J CLIN ONCOL S, V28, p18s
  5. Bernard-Marty C, 2004, ONCOLOGIST, V9, P617, DOI 10.1634/theoncologist.9-6-617
  6. Bianchi G, 2009, ANTI-CANCER DRUG, V20, P616, DOI 10.1097/CAD.0b013e32832b2ea0
  7. Blum JL, 1999, J CLIN ONCOL, V17, P485
  8. Borgstrom P, 1996, CANCER RES, V56, P4032
  9. Brufsky AM, 2011, J CLIN ONCOL, V29, P4286, DOI 10.1200/JCO.2010.34.1255
  10. Carrick S, 2009, COCHRANE DB SYST REV, V2
  11. Crown J, 2010, J CLIN ONCOL S, V28, p18s
  12. Dal Lago L, 2008, ONCOLOGIST, V13, P845, DOI 10.1634/theoncologist.2007-0233
  13. Dodd LE, 2008, J CLIN ONCOL, V26, P3791, DOI 10.1200/JCO.2008.16.1711
  14. Ebos JML, 2009, CANCER CELL, V15, P232, DOI 10.1016/j.ccr.2009.01.021
  15. Ershler WB, 2006, ONCOLOGIST, V11, P325, DOI 10.1634/theoncologist.11-4-325
  16. Escudier B, 2007, NEW ENGL J MED, V356, P125, DOI 10.1056/NEJMoa060655
  17. Findlay M, 2008, ANN ONCOL, V19, P212, DOI 10.1093/annonc/mdm285
  18. Fleming TR, 2004, J INFECT DIS, V190, P666, DOI 10.1086/422603
  19. Fox SB, 2007, BREAST CANCER RES, V9, DOI 10.1186/bcr1796
  20. Hansen S, 2000, CLIN CANCER RES, V6, P139
  21. Llovet JM, 2008, NEW ENGL J MED, V359, P378, DOI 10.1056/NEJMoa0708857
  22. Miles D, 2011, J CLIN ONCOL, V29, P83, DOI 10.1200/JCO.2010.30.2794
  23. Miles DW, 2010, J CLIN ONCOL, V28, P3239, DOI 10.1200/JCO.2008.21.6457
  24. Miller K, 2007, NEW ENGL J MED, V357, P2666, DOI 10.1056/NEJMoa072113
  25. Miller KD, 2005, J CLIN ONCOL, V23, P792, DOI 10.1200/JCO.2005.05.098
  26. Moreno-Aspitia A, 2009, J CLIN ONCOL, V27, P11, DOI 10.1200/JCO.2007.15.5242
  27. Olin JJ, 2000, ONCOLOGY-NY, V14, P629
  28. O'Shaughnessy JA, 2001, ANN ONCOL, V12, P1247, DOI 10.1023/A:1012281104865
  29. Paez-Ribes M, 2009, CANCER CELL, V15, P220, DOI 10.1016/j.ccr.2009.01.027
  30. Presta LG, 1997, CANCER RES, V57, P4593
  31. Robert NJ, 2011, J CLIN ONCOL, V29, P1252, DOI 10.1200/JCO.2010.28.0982
  32. Robert NJ, 2009, J CLIN ONCOL S, V27, p18s
  33. Roy V, 2009, BREAST CANCER RES TR, V116, P31, DOI 10.1007/s10549-008-0268-y
  34. Schneider BP, 2005, J CLIN ONCOL, V23, P1782, DOI 10.1200/JCO.2005.12.017
  35. Therasse P, 2000, J NATL CANCER I, V92, P205, DOI 10.1093/jnci/92.3.205
  36. WEIDNER N, 1992, J NATL CANCER I, V84, P1875, DOI 10.1093/jnci/84.24.1875
  37. WEIDNER N, 1991, NEW ENGL J MED, V324, P1, DOI 10.1056/NEJM199101033240101
  38. Wilhelm S, 2006, NAT REV DRUG DISCOV, V5, P835, DOI 10.1038/nrd2130
  39. Wilhelm SM, 2008, MOL CANCER THER, V7, P3129, DOI 10.1158/1535-7163.MCT-08-0013
  40. Wilhelm SM, 2004, CANCER RES, V64, P7099, DOI 10.1158/0008-5472.CAN-04-1443
  41. Willett CG, 2004, NAT MED, V10, P145, DOI 10.1038/nm988
  42. Yuan F, 1996, P NATL ACAD SCI USA, V93, P14765, DOI 10.1073/pnas.93.25.14765

Coleções
Artigos e Materiais de Revistas Científicas - HC/ICESP
Carregar mais