Weekly paclitaxel and concurrent pazopanib following doxorubicin and cyclophosphamide as neoadjuvant therapy for HER-negative locally advanced breast cancer: NSABP?Foundation FB-6, a phase II study

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• 作者：A. R. Tan ; H. Johannes ; P. Rastogi ; S. A. Jacobs…
• 关键词：Pazopanib ; Paclitaxel ; Breast cancer ; Neoadjuvant chemotherapy
• 刊名：Breast Cancer Research and Treatment
• 出版年：2015
• 出版时间：January 2015
• 年：2015
• 卷：149
• 期：1
• 页码：163-169
• 全文大小：188 KB
• 参考文献：1. Bear HD, Tang G, Rastogi P et al (2012) Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med 366:310-20 CrossRef
  2. von Minckwitz G, Eidtmann H, Rezai M et al (2012) Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med 366:299-09 CrossRef
  3. Harris PA, Boloor A, Cheung M et al (2008) Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methyl-benzenesulfonamide (Pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor. J Med Chem 51:4632-640 CrossRef
  4. Hurwitz HI, Dowlati A, Saini S et al (2009) Phase I trial of pazopanib in patients with advanced cancer. Clin Cancer Res 15:4220-227 CrossRef
  5. Sternberg CN, Davis ID, Mardiak J et al (2010) Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28:1061-068 CrossRef
  6. van der Graaf WT, Blay JY, Chawla SP et al (2012) Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 379:1879-886 CrossRef
  7. Tan AR, Dowlati A, Jones SF et al (2010) Phase I study of pazopanib in combination with weekly paclitaxel in patients with advanced solid tumors. Oncologist 15:1253-261 CrossRef
  8. Sargent DJ, Chan V, Goldberg RM (2001) A three-outcome design for phase II clinical trials. Control Clin Trials 22:117-25 CrossRef
  9. Rastogi P, Anderson SJ, Bear HD et al (2008) Preoperative chemotherapy: updates of national surgical adjuvant breast and bowel project protocols B-18 and B-27. J Clin Oncol 26:778-85 CrossRef
  10. von Minckwitz G, Raab G, Caputo A et al (2005) Doxorubicin with cyclophosphamide followed by docetaxel every 21?days compared with doxorubicin and docetaxel every 14?days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol 23:2676-685 CrossRef
  11. Sparano JA, Wang M, Martino S et al (2008) Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 358:1663-671 CrossRef
  12. Ein-Gal SY, Tsang W, Alger B et al (2013) Updated interim analysis of UCI 091-53: a phase II, single arm study of pazopanib and paclitaxel as first-line treatment for subjects with unresectable advanced melanoma. J Clin Oncol 31(Suppl):Abstr 9082
  13. Srinivas S, Narayanan S, Harsham LC et al (2014) Phase II trial of pazopanib and weekly paclitaxel in metastatic urothelial cancer. J Clin Oncol 32(Suppl):Abstr 299
  14. Seidman AD, Hudis CA, Albanell J et al (1998) Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer. J Clin Oncol 16:3353-361
  15. Bible KC, Suman VJ, Molina JR et al (2014) A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma: MC057H. J Clin Endocrinol Metab 99:1687-693 CrossRef
  16. Taylor SK, Chia S, Dent S et al (2010) A phase II study of pazopanib in patients with recurrent or metastatic invasive breast carcinoma: a trial of the Princess Margaret Hospital phase II consortium. Oncologist 15:810-18 CrossRef
  17. Yardley D, Barton J, Hendricks C et al (2012) Neoadjuvant sunitinib administered with weekly paclitaxel/carboplatin in patients with locally advanced triple-negative breast cancer: preliminary results from a ph
• 作者单位：A. R. Tan (1) (2) (3)
  H. Johannes (4)
  P. Rastogi (1) (5)
  S. A. Jacobs (1) (5)
  A. Robidoux (1) (6)
  P. J. Flynn (1) (7)
  M. P. Thirlwell (1) (8)
  L. Fehrenbacher (1) (9)
  P. J. Stella (1) (10)
  R. Goel (1) (11)
  T. B. Julian (1) (12)
  L. Provencher (1) (13)
  M. J. Bury (1) (14)
  K. Bhatt (15)
  C. E. Geyer Jr. (1) (16)
  S. M. Swain (1) (17)
  E. P. Mamounas (1) (18)
  N. Wolmark (1) (12)
  
  1. National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA, USA
  2. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
  3. Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, 28204, USA
  4. International Drug Development Institute, Louvain-la-Neuve, Belgium
  5. University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
  6. Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada
  7. CCOP, Metro-Minnesota, St Louis Park, MN, USA
  8. Montréal General Hospital, Montreal, QC, Canada
  9. Kaiser Permanente Northern California, Vallejo, CA, USA
  10. CCOP, Michigan Cancer Research Consortium Community Clinical Oncology Program, Ann Arbor, MI, USA
  11. The Ottawa Hospital Regional Cancer Centre, Ottawa, ON, Canada
  12. Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA, USA
  13. Centre Hospitalier Universitaire de Quebec, H?pital du Saint-Sacrement, Quebec City, QC, Canada
  14. CCOP, Grand Rapids Clinical Oncology Program, Grand Rapids, MI, USA
  15. GlaxoSmithKline, Philadelphia, PA, USA
  16. Virginia Commonwealth University Massey Cancer Center, Richmond, VA, USA
  17. Medstar Washington Hospital Center, Washington Cancer Institute, Washington, DC, USA
  18. University of Florida Health Cancer Center, Orlando, FL, USA
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  
• 出版者：Springer Netherlands
• ISSN：1573-7217

文摘

This multicenter single-arm phase II study evaluated the addition of pazopanib to concurrent weekly paclitaxel following doxorubicin and cyclophosphamide as neoadjuvant therapy in human epidermal growth factor receptor (HER2)-negative locally advanced breast cancer (LABC). Patients with HER2-negative stage III breast cancer were treated with doxorubicin 60?mg/m2 and cyclophosphamide 600?mg/m2 for four cycles every 3?weeks followed by weekly paclitaxel 80?mg/m2 on days 1, 8, and 15 every 28?days for four cycles concurrently with pazopanib 800?mg orally daily prior to surgery. Post-operatively, pazopanib was given daily for 6?months. The primary endpoint was pathologic complete response (pCR) in the breast and lymph nodes. Between July 2009 and March 2011, 101 patients with stage IIIA–C HER2-negative breast cancer were enrolled. The pCR rate in evaluable patients who initiated paclitaxel and pazopanib was 17?% (16/93). The pCR rate was 9?% (6/67) in hormone receptor-positive tumors and 38?% (10/26) in triple-negative tumors. Pre-operative pazopanib was completed in only 39?% of patients. The most frequent grade 3 and 4 adverse events during paclitaxel and pazopanib were neutropenia (27?%), diarrhea (5?%), ALT and AST elevations (each 5?%), and hypertension (5?%). Although the pCR rate of paclitaxel and pazopanib following AC chemotherapy given as neoadjuvant therapy in women with LABC met the pre-specified criteria for activity, there was substantial toxicity, which led to a high discontinuation rate of pazopanib. The combination does not appear to warrant further evaluation in the neoadjuvant setting for breast cancer.