J Breast Cancer.  2011 Jun;14(2):129-134. 10.4048/jbc.2011.14.2.129.

Comparison of Doxorubicin Plus Docetaxel Neoadjuvant Chemotherapy with Doxorubicin Plus Vinorelbine in Primary Breast Cancer

• Gwak G
• Kim JY
• Park K
• Shin YJ
• Cho H
• Park SJ
• Yang GH
• Bae BN
• Kim KW
• Han S

• KMID: 2286512
• DOI: http://doi.org/10.4048/jbc.2011.14.2.129

Abstract

PURPOSE
This study was performed to compare the therapeutic efficacy and toxicity of doxorubicin plus docetaxel neoadjuvant chemotherapy (NC) with doxorubicin plus vinorelbine NC.
METHODS
Fifty-three patients underwent 4 cycles of NC consisted of intravenous injection of doxorubicin (50 mg/m2) plus docetaxel (75 mg/m2) administered every 3 weeks (AD), while 49 patients underwent 4 cycles of NC consisted of intravenous injection of doxorubicin (50 mg/m2) and vinorelbine (25 mg/m2) administered every 3 weeks (AN). Response rate and treatment-related toxicities were analyzed by administered chemotherapeutics. Response to NC was also analyzed according to clinicobiological characteristics of the primary tumors.
RESULTS
Clinical response was observed in 66% with AN and 81.6% with AD chemotherapy. A complete pathologic response (pCR) was confirmed in 6 patients (11.3%) with AN and in 7 patients (14.3%) with AD after the surgery. Response rate was significantly higher in AD compared with AN (p=0.038), but there was no significant difference between the two group regard to pCR rate. Breast conserving surgery (BCS) was performed in 35.8% of AN group, whereas 20 patients (40.8%) of AD group underwent BCS. The patients with HER2-amplified tumor showed significantly increased response to both types of NC. Pathologic complete response was confirmed in 9 (39.1%) out of 23 HER2-amplified tumors, whereas only 4 (5.1%) of 79 HER2-nonamplified tumors showed pathologic complete response. Febrile neutropenia occurred in 22.6% of total 212 cycles in AN and 38.8% of total 196 cycles in AD. Grade 3/4 neutropenia was observed in 39.6% in AN and 43.9% in AD. Grade 3 mucositis was observed in 26.4% with AN and in 40.8% with AD.
CONCLUSION
There was no significant increase of pCR by AD compared with AN. Long-term follow-up results of our study indicate that clinical outcome after NC was significantly associated with initial response to NC regardless of therapeutic regimens.

Keyword

Breast neoplasms; Docetaxel; Doxorubicin; Neoadjuvant chemotherapy; Toxicity

MeSH Terms

Breast
Breast Neoplasms
Doxorubicin
Follow-Up Studies
Humans
Injections, Intravenous
Mastectomy, Segmental
Mucositis
Neutropenia
Polymerase Chain Reaction
Taxoids
Vinblastine
Doxorubicin
Taxoids
Vinblastine

Figure

• 

  Figure 1 Disease-free survivals according to response to doxorubicin and vinorelbine neoadjuvant chemotherapy. SD=stable disease; PR=partial response; pCR=complete pathologic response.

Reference

1. Bonadonna G. Evolving concepts in the systemic adjuvant treatment of breast cancer. Cancer Res. 1992. 52:2127–2137.

2. Kaufmann M, Hortobagyi GN, Goldhirsch A, Scholl S, Makris A, Valagussa P, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol. 2006. 24:1940–1949.

3. Mauri D, Pavlidis N, Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst. 2005. 97:188–194.

4. Kuerer HM, Newman LA, Smith TL, Ames FC, Hunt KK, Dhingra K, et al. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol. 1999. 17:460–469.

5. Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, et al. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003. 21:4165–4174.

6. Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998. 16:2672–2685.

7. van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001. 19:4224–4237.

8. Smith IC, Heys SD, Hutcheon AW, Miller ID, Payne S, Gilbert FJ, et al. Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol. 2002. 20:1456–1466.

9. Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2006. 24:2019–2027.

10. De Laurentiis M, Cancello G, D'Agostino D, Giuliano M, Giordano A, Montagna E, et al. Taxane-based combinations as adjuvant chemotherapy of early breast cancer: a meta-analysis of randomized trials. J Clin Oncol. 2008. 26:44–53.

11. Mansi JL, Yellowlees A, Lipscombe J, Earl HM, Cameron DA, Coleman RE, et al. Five-year outcome for women randomised in a phase III trial comparing doxorubicin and cyclophosphamide with doxorubicin and docetaxel as primary medical therapy in early breast cancer: an Anglo-Celtic Cooperative Oncology Group study. Breast Cancer Res Treat. 2010. 122:787–794.

12. Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008. 26:778–785.

13. Ellis P, Barrett-Lee P, Johnson L, Cameron D, Wardley A, O'Reilly S, et al. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial. Lancet. 2009. 373:1681–1692.

14. Palmeri S, Leonardi V, Tamburo De Bella M, Morabito A, Vaglica M, Accurso V, et al. Doxorubicin-docetaxel sequential schedule: results of front-line treatment in advanced breast cancer. Oncology. 2002. 63:205–212.

15. Steger GG, Galid A, Gnant M, Mlineritsch B, Lang A, Tausch C, et al. Pathologic complete response with six compared with three cycles of neoadjuvant epirubicin plus docetaxel and granulocyte colony-stimulating factor in operable breast cancer: results of ABCSG-14. J Clin Oncol. 2007. 25:2012–2018.

16. Montagna E, Bagnardi V, Rotmensz N, Viale G, Pruneri G, Veronesi P, et al. Pathological complete response after preoperative systemic therapy and outcome: relevance of clinical and biologic baseline features. Breast Cancer Res Treat. 2010. 124:689–699.

17. Park K, Kim J, Lim S, Han S. Topoisomerase II-alpha (topoII) and HER2 amplification in breast cancers and response to preoperative doxorubicin chemotherapy. Eur J Cancer. 2003. 39:631–634.

18. Thor AD, Berry DA, Budman DR, Muss HB, Kute T, Henderson IC, et al. erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer. J Natl Cancer Inst. 1998. 90:1346–1360.

19. Paik S, Bryant J, Park C, Fisher B, Tan-Chiu E, Hyams D, et al. erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer. J Natl Cancer Inst. 1998. 90:1361–1370.

20. Pritchard KI, Shepherd LE, O'Malley FP, Andrulis IL, Tu D, Bramwell VH, et al. HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med. 2006. 354:2103–2111.