Abstract
Purpose
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.
Methods
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.
Results
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 %).
Conclusions
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.
Similar content being viewed by others
References
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 90:1740–1746
Blum JL, Dieras V, Lo Russo PM, Horton J, Rutman O, Buzdar A, Osterwalder B (2001) Multicenter, phase II study of capecitabine in taxane-pretreated metastatic breast carcinoma patients. Cancer 92:1759–1768
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 24:4384–4390
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 17:2639–2648
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 45:228–247
Fendly BM, Winget M, Hudziak RM, Lipari MT, Napier MA, Ullrich A (1990) Characterization of murine monoclonal antibodies reactive to either the human epidermal growth factor receptor or HER2/neu gene product. Cancer Res 50:1550–1558
Gradishar WJ, Meza LA, Amin B, Samid D, Hill T, Chen YM, Lower EE, Marcom PK (2004) Capecitabine plus paclitaxel as front-line combination therapy for metastatic breast cancer: a multicenter phase II study. J Clin Oncol 22:2321–2327
Michalaki V, Fotiou S, Gennatas S, Gennatas C (2010) Trastuzumab plus capecitabine and docetaxel as first-line therapy for HER2-positive metastatic breast cancer: phase II results. Anticancer Res 30:3051–3054
Morris PG, McArthur HL, Hudis CA (2009) Therapeutic options for metastatic breast cancer. Expert Opin Pharmacother 10:967–981
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 15:2894–2904
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 24:2786–2792
Seidman A, Hudis C, Pierri MK, Shak S, Paton V, Ashby M, Murphy M, Stewart SJ, Keefe D (2002) Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol 20:1215–1221
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 26:1642–1649
Seshadri R, Firgaira FA, Horsfall DJ, McCaul K, Setlur V, Kitchen P (1993) Clinical significance of HER-2/neu oncogene amplification in primary breast cancer. J Clin Oncol 11:1936–1942
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER2-2/neu oncogene. Science 235:177–182
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 344:783–792
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
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 29:149–150
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 20:719–726
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 28:976–983
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 25:118–145
Conflict of interest
The authors declare no conflict of interest.
Author information
Authors and Affiliations
Consortia
Corresponding author
Rights and permissions
About this article
Cite this article
Tonyali, O., Benekli, M., Berk, V. et al. Efficacy and toxicity of Trastuzumab and Paclitaxel plus Capecitabine in the first-line treatment of HER2-positive metastatic breast cancer. J Cancer Res Clin Oncol 139, 981–986 (2013). https://doi.org/10.1007/s00432-013-1409-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-013-1409-1