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Efficacy of Dose Dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel versus Conventional Dose Doxorubicin, Cyclophosphamide Followed by Paclitaxel or Docetaxel in Patients with Node-Positive Breast Cancer

  • Yazilitas, Dogan (Department of Medical Oncology, Ankara Numune Education and Research Hospital) ;
  • Sendur, Mehmet Ali Nahit (Department of Medical Oncology, Faculty of Medicine, Yildirim Beyazit University) ;
  • Karaca, Halit (Gaziosmapasa University Faculty of Medicine, Department of Medical Oncology) ;
  • Ozdemir, Nuriye (Department of Medical Oncology, Faculty of Medicine, Yildirim Beyazit University) ;
  • Aksoy, Sercan (Department of Medical Oncology, Hacettepe University Cancer Institute) ;
  • Berk, Veli (Gaziosmapasa University Faculty of Medicine, Department of Medical Oncology) ;
  • Yazici, Ozan (Department of Medical Oncology, Ankara Numune Education and Research Hospital) ;
  • Ozturk, Banu (Gaziosmapasa University Faculty of Medicine, Department of Medical Oncology) ;
  • Ozkan, Metin (Gaziosmapasa University Faculty of Medicine, Department of Medical Oncology) ;
  • Zengin, Nurullah (Department of Medical Oncology, Ankara Numune Education and Research Hospital) ;
  • Altundag, Kadri (Department of Medical Oncology, Hacettepe University Cancer Institute)
  • 발행 : 2015.03.09

초록

Background: Adding taxanes to adjuvant antracycline and cyclophosphamide (AC) in combination may provide significant improvement in node-positive and high risk node-negative breast cancer (BC) patients. However, the optimal dose and the role of dose-dense (DD) chemotherapy have yet to be determined. The aim of this study was to compare the efficacy of a DD paclitaxel (P)-AC combination with conventional weekly P-AC or docetaxel D-AC combinations in patients with node-positive breast cancer. Materials and Methods: Newly diagnosed 280 node-positive BC patients diagnosed from 1998 to 2013 in three clinics were retrospectively analyzed. Demographic and medical data were collected from the medical charts. Patients were categorized to 3 groups according to treatment arms: arm A, ddAC-P; arm B, weekly P and AC combination; and arm C; T and AC combination. Adjuvant trastuzumab was added for HER2-positive patients. Kaplan-Meier survival analysis was carried out for disease free survival (DFS) and overall survival (OS). The log-rank test was used to examine the statistical significance of the differences observed between the groups. Two-sided P values <0.05 were considered statistically significant. Results: Of the total of 280 patients, 101 were in arm A, 114 in arm B and 65 in arm C.The median ages were 49, 50 and 46, respectively (p=0.11). Median follow-up was 39 (3-193) months. Stage, lymphovascular and perineural invasion, receptor patern, and menopausal status were similar in the 3 treatment arms, but HER2 positivity was significantly lower in arm A, compared to arms B and C (25.7%, 53.1%, 41.5% in arms A, B and C, respectively; p<0.001). Also grade 3 tumors were significantly less frequent in treatment arm A compared to arm B and C (27.3%, 56.8% and 49.2%, respectively, p=0.01). Afterunivariate and multivariate analysis were performed, 3-year DFS rates were 89%, 81%, and 75%, respectively (p=0.12) and three year OS rates were 96.6%, 89%, and 75% (p=0.62). Conclusions: In this study, no significant difference was found between adjuvant dose dense and conventional taxane treatment regimens.

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참고문헌

  1. Bang SM, Heo DS, Lee KH, et al (2000). Adjuvant doxorubicin and cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in premenopausal women with axillary lymph node positive breast carcinoma. Cancer, 89, 2521-6. https://doi.org/10.1002/1097-0142(20001215)89:12<2521::AID-CNCR2>3.0.CO;2-F
  2. Bonadonna G, Valagussa P, Moliterni A, et al (1995). Adjuvant cyclophosphamide, methotrexate, and fluorouracil in nodepositive breast cancer: the results of 20 years of follow-up. N Engl J Med, 332, 901-6. https://doi.org/10.1056/NEJM199504063321401
  3. Bonadonna G, Zambetti M, Moliterni A, et al (2004). Clinical relevance of different sequencing of doxorubicin and cyclophosphamide, methotrexate, and Fluorouracil in operable breast cancer. J Clin Oncol, 22, 1614-20. https://doi.org/10.1200/JCO.2004.07.190
  4. Bontenbal M, Creemers GJ, Braun HJ, et al (2005). Phase II to III study comparing doxorubicin and docetaxel with fluorouracil, doxorubicin, and cyclophosphamide as firstline chemotherapy in patients with metastatic breast cancer: results of a dutch community setting trial for the clinical trial group of the comprehensive cancer centre. J Clin Oncol, 23, 7081-8. https://doi.org/10.1200/JCO.2005.06.236
  5. Citron ML, Berry DA, Cirrincione C, et al (2003). Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol, 21, 1431-9. https://doi.org/10.1200/JCO.2003.09.081
  6. Early Breast Cancer Trialists' Collaborative Group (1998). Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet, 352, 930-42. https://doi.org/10.1016/S0140-6736(98)03301-7
  7. Early Breast Cancer Trialists' Collaborative Group (2005). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet, 365, 1687-717. https://doi.org/10.1016/S0140-6736(05)66544-0
  8. Early Breast Cancer Trialists' Collaborative G, Peto R, Davies C, et al (2012). Comparisons between different polychemotherapy regimens for early breast cancer: metaanalyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet, 379, 432-44. https://doi.org/10.1016/S0140-6736(11)61625-5
  9. Eiermann W, Pienkowski T, Crown J, et al (2011). Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial. J Clin Oncol, 29, 3877-84. https://doi.org/10.1200/JCO.2010.28.5437
  10. Ellis GK, Livingston RB, Gralow JR, et al (2002). Dose-dense anthracycline-based chemotherapy for node-positive breast cancer. J Clin Oncol, 20, 3637-43. https://doi.org/10.1200/JCO.2002.12.113
  11. Gogas H, Dafni U, Karina M, et al (2012). Postoperative dose-dense sequential versus concomitant administration of epirubicin and paclitaxel in patients with node-positive breast cancer: 5-year results of the Hellenic Cooperative Oncology Group HE 10/00 phase III Trial. Breast Cancer Res Treat, 132, 609-19. https://doi.org/10.1007/s10549-011-1913-4
  12. Gogia A, Raina V, Deo SV, et al (2014). Taxane and anthracycline based neoadjuvant chemotherapy for locally advanced breast cancer: institutional experience. Asian Pac J Cancer Prev, 15, 1989-92. https://doi.org/10.7314/APJCP.2014.15.5.1989
  13. Henderson IC, Berry DA, Demetri GD, et al (2003). Improved outcomes from adding sequential Paclitaxel but not from escalating Doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol, 21, 976-83. https://doi.org/10.1200/JCO.2003.02.063
  14. Jones RL, Walsh G, Ashley S, et al (2009). A randomised pilot Phase II study of doxorubicin and cyclophosphamide (AC) or epirubicin and cyclophosphamide (EC) given 2 weekly with pegfilgrastim (accelerated) vs 3 weekly (standard) for women with early breast cancer. Br J Cancer, 100, 305-10. https://doi.org/10.1038/sj.bjc.6604862
  15. Kimura M, Tominaga T, Takatsuka Y, et al (2010). Randomized trial of cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil with node-positive breast cancer in Japan. Breast Cancer, 17, 190-8. https://doi.org/10.1007/s12282-009-0132-x
  16. Levine MN, Bramwell VH, Pritchard KI, et al (1998). Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol, 16, 2651-8. https://doi.org/10.1200/JCO.1998.16.8.2651
  17. Mackey JR, Martin M, Pienkowski T, et al (2013). Adjuvant docetaxel, doxorubicin, and cyclophosphamide in nodepositive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial. Lancet Oncol, 14, 72-80. https://doi.org/10.1016/S1470-2045(12)70525-9
  18. Martin M, Segui MA, Anton A, et al (2010). Adjuvant docetaxel for high-risk, node-negative breast cancer. N Engl J Med, 363, 2200-10. https://doi.org/10.1056/NEJMoa0910320
  19. Martin M, Villar A, Sole-Calvo A, et al (2003). Doxorubicin in combination with fluorouracil and cyclophosphamide (i.v. FAC regimen, day 1, 21) versus methotrexate in combination with fluorouracil and cyclophosphamide (i.v. CMF regimen, day 1, 21) as adjuvant chemotherapy for operable breast cancer: a study by the GEICAM group. Ann Oncol, 14, 833-42. https://doi.org/10.1093/annonc/mdg260
  20. Morris PG, Dickler M, McArthur HL, et al (2009). Dosedense adjuvant Doxorubicin and cyclophosphamide is not associated with frequent short-term changes in left ventricular ejection fraction. J Clin Oncol, 27, 6117-23. https://doi.org/10.1200/JCO.2008.20.2952
  21. Nabholtz JM, Falkson C, Campos D, et al (2003). Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trial. J Clin Oncol, 21, 968-75. https://doi.org/10.1200/JCO.2003.04.040
  22. Norton L, Simon R (1986). The Norton-Simon hypothesis revisited. Cancer Treat Rep, 70, 163-9.
  23. Ozdemir N, Aksoy S, Zengin N, et al (2012). Taxanes in the adjuvant treatment of node-negative breast cancer patients. J BUON, 17, 27-32.
  24. Sakr H, Hamed RH, Anter AH, et al (2013). Sequential docetaxel as adjuvant chemotherapy for node-positive or/and T3 or T4 breast cancer: clinical outcome (Mansoura University). Med Oncol, 30, 457. https://doi.org/10.1007/s12032-013-0457-3
  25. Senkus E, Kyriakides S, Penault-Llorca F, et al (2013). Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 24, 7-23.
  26. Siegel R, Ma J, Zou Z, et al (2014). Cancer statistics, 2014. CA Cancer J Clin, 64, 9-29. https://doi.org/10.3322/caac.21208
  27. Slamon DJ, Clark GM, Wong SG, et al (1987). Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science, 235, 177-82. https://doi.org/10.1126/science.3798106
  28. Sparano JA, Wang M, Martino S, et al (2005). Phase III study of doxorubicin cyclophosphamide followed by paclitaxel or docetaxel given every 3 weeks or weekly in patients with axillary node-positive or high-risk node-negative breast cancer: results of North American Breast Cancer Intergroup Trial E1199. Breast Cancer Res Treat, 94, 516.
  29. Sparano JA, Wang M, Martino S, et al (2008). Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med, 358, 1663-71. https://doi.org/10.1056/NEJMoa0707056
  30. Swain SM, Tang G, Geyer CE, et al (2013). Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol, 31, 3197-204. https://doi.org/10.1200/JCO.2012.48.1275
  31. Theriault RL, Carlson RW, Allred C, et al (2013). Breast cancer, version 3.2013: featured updates to the NCCN guidelines. J Natl Compr Canc Netw, 11, 753-60. https://doi.org/10.6004/jnccn.2013.0098
  32. Venturini M, Del Mastro L, Aitini E, et al (2005). Dose-dense adjuvant chemotherapy in early breast cancer patients: results from a randomized trial. J Natl Cancer Inst, 97, 1724-33. https://doi.org/10.1093/jnci/dji398

피인용 문헌

  1. Prognostic Value of Chemotherapy-Induced Amenorrhea in Breast Cancer: a Meta-Analysis vol.16, pp.14, 2015, https://doi.org/10.7314/APJCP.2015.16.14.5939