Efficacy and toxicity of Trastuzumab and Paclitaxel plus Capecitabine in the first-line treatment of HER2-positive metastatic breast cancer
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Combinations of trastuzumab with paclitaxel or capecitabine are effective therapies in human epidermal growth factor 2 (HER2)-positive metastatic breast cancer (MBC). This retrospective study evaluated the efficacy and toxicity of trastuzumab and paclitaxel plus capecitabine in the first-line therapy for patients with HER2-positive MBC.
A total of 40 patients with HER2-positive MBC treated between January 2008 and January 2011 were evaluated retrospectively in 6 institutions. Three patients with performance score of 3 who died before response assessment were excluded from the study. The patients were given trastuzumab 8 mg/kg loading dose followed by then 6 mg/kg dose on day 1 and paclitaxel 175 mg/m2 on day 1 plus capecitabine 825 mg/m2 twice daily on days 1–14 every 3 weeks.
A total of 287 cycles of chemotherapy were administered with a median of 8 treatment cycles per patient (range 3–12). Median follow-up period was 24.7 months (range 4.7–51). There were 9 patients (24.3 %) with complete responses, 21 (56.8 %) with partial responses, 4 (10.8 %) with stable disease and 3 (8.1 %) with progressive disease resulting in an overall response rate (ORR) of 81.1 %. Median progression-free survival and overall survival were 14 and 38.4 months, respectively. Rates of grade 3 adverse events were neutropenia (n = 4, 10.8 %), cardiac dysfunction (n = 1, 2.7 %), hand-foot syndrome (n = 2, 5.4 %), nausea (n = 2, 5.4 %), vomiting (n = 2, 5.4 %), fatigue (n = 1, 2.7 %), diarrhea (n = 1, 2.7 %), neuropathy (n = 1, 2.7 %) and alopecia (n = 1, 2.7 %).
Combination of trastuzumab and paclitaxel plus capecitabine is an effective and well-tolerated regimen in the first-line therapy for women with HER2-positive MBC.
KeywordsChemotherapy Breast cancer Metastasis HER2
Conflict of interest
The authors declare no conflict of interest.
- American Cancer Society (2010) Cancer facts and figures 2010. www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-026238.pdf. Accessed 1 Nov 2010
- Batista N, Perez-Manga G, Constenla M, Ruiz A, Carabantes F, Castellanos J, Gonzalez Barón M, Villman K, Söderberg M, Ahlgren J, Casinello J, Regueiro P, Murias A (2004) Phase II study of capecitabine in combination with paclitaxel in patients with anthracycline-pretreated advanced/metastatic breast cancer. Br J Cancer 90:1740–1746PubMedGoogle Scholar
- Blum JL, Dees EC, Chacko A, Doane L, Ethirajan S, Hopkins J, McMahon R, Merten S, Negron A, Neubauer M, Ilegbodu D, Boehm KA, Asmar L, O’Shaughnessy JA (2006) Phase II trial of capecitabine and weekly paclitaxel as first-line therapy for metastatic breast cancer. J Clin Oncol 24:4384–4390PubMedCrossRefGoogle Scholar
- Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, Wolter JM, Paton V, Shak S, Lieberman G, Slamon DJ (1999) Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 17:2639–2648PubMedGoogle Scholar
- Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247PubMedCrossRefGoogle Scholar
- National Comprehensive Cancer Network (2011) NCCN clinical practice guidelines in oncology. Breast cancer, V.2.2011. www.nccn.org/professionals/physician_gls/PDF/breast.pdf. Accessed 2 Jan 2011
- Press MF, Bernstein L, Thomas PA, Meisner LF, Zhou JY, Ma Y, Hung G, Robinson RA, Harris C, El-Naggar A, Slamon DJ, Phillips RN, Ross JS, Wolman SR, Flom KJ (1997) HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas. J Clin Oncol 15:2894–2904PubMedGoogle Scholar
- Robert N, Leyland-Jones B, Asmar L, Belt R, Ilegbodu D, Loesch D, Raju R, Valentine E, Sayre R, Cobleigh M, Albain K, McCullough C, Fuchs L, Slamon D (2006) Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol 24:2786–2792PubMedCrossRefGoogle Scholar
- Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C (2008) Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol 26:1642–1649PubMedCrossRefGoogle Scholar
- Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792PubMedCrossRefGoogle Scholar
- Tonyali O, Coskun U, Sener N, Inanc M, Akman T, Oksuzoglu B, Ozdemir NY, Yazilitas D, Benekli M, Uner A, Yamac D, Demirci U, Yildiz R, Karaca H, Unal OU, Bal O, Gumus M, Buyukberber S, Anatolian Society of Medical Oncology (ASMO) (2012) Nine-week trastuzumab treatment versus 52-week trastuzumab treatment for HER2-positive early-stage breast cancer. J Cancer Res Clin Oncol doi. doi: 10.1007/s00432-012-1296-x Google Scholar
- Valero V, Forbes J, Pegram MD, Pienkowski T, Eiermann W, von Minckwitz G, Roche H, Martin M, Crown J, Mackey JR, Fumoleau P, Rolski J, Mrsic-Krmpotic Z, Jagiello-Gruszfeld A, Riva A, Buyse M, Taupin H, Sauter G, Press MF, Slamon DJ (2011) Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens. J Clin Oncol 29:149–150PubMedCrossRefGoogle Scholar
- Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Slamon DJ, Murphy M, Novotny WF, Burchmore M, Shak S, Stewart SJ, Press M (2002) Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20:719–726PubMedCrossRefGoogle Scholar
- Wardley AM, Pivot X, Morales-Vasquez F, Zetina LM, de Fátima Dias Gaui M, Reyes DO, Jassem J, Barton C, Button P, Hersberger V, Torres AA (2010) Randomized phase II trial of first-line trastuzumab plus docetaxel and capecitabine compared with trastuzumab plus docetaxel in HER2-positive metastatic breast cancer. J Clin Oncol 28:976–983PubMedCrossRefGoogle Scholar
- Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF, American Society of Clinical Oncology, College of American Pathologists (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118–145PubMedCrossRefGoogle Scholar