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Article / Publication Details
The pivotal phase II and III Herceptin® trials proved the efficacy and safety of second- or third-line single-agent Herceptin and first-line Herceptin in combination with chemotherapy, respectively. In the current trial, 114 patients were randomized to one of two dose groups of first-line Herceptin monotherapy: standard dose of 4 mg/ kg initial dose followed by 2 mg/kg intravenous (i.v.) weekly; or high dose of 8 mg/kg initial dose followed by 4 mg/kg i.v. weekly. The regimen was generally well tolerated. A similar incidence of adverse events was demonstrated in the two dose groups with the possible exception of acute infusion-related events such as fever and chills as well as rash and dyspnea, which appear to be more prevalent in the higher dose group. The overall response rate was 26% and response rates were similar between the two dose groups (24% for the standard Herceptin dose group and 28% for the high Herceptin dose group). Subgroup analysis determined a higher response rate in IHC 3+ patients (35%) and FISH-positive patients (41%). When women with stable disease for ≧6 months were included with responders, the clinical benefit rate in IHC 3+ patients was 47%. Median survival was 24.4 months, which is comparable with the survival rate seen in the pivotal phase III combination trial (25 months). Therefore, single-agent Herceptin is an important new option for the first-line treatment of HER2-positive metastatic breast cancer patients.
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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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- Baselga J, Tripathy D, Mendelsohn J, Baughman S, Benz CC, Dantis L, Sklarin NT, Seidman AD, Hudis CA, Moore J, Rosen RP, Twaddell T, Henderson IC, Norton L: Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol 1996;14:737–744.
- Baselga J, Norton L, Abanell J, Kim Y-M, Mendelsohn J: Recombinant humanized anti-HER2 antibody (HerceptinTM) enhances the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. Cancer Res 1998;58:2825–2831.
- Baselga J: Herceptin® alone or in combination with chemotherapy in the treatment of HER2-positive metastatic breast cancer: pivotal trials. Oncology 2001;61(suppl 2):14–21.
- Benz CC, Scott, GK, Sarup JC, Johnson RM, Tripathy D, Coronado E, Shepard HM, Osborne CK: Estrogen-dependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu. Breast Cancer Res Treat 1992;24:85–95.
- Carter P, Presta L Gorman CM, Ridgway JB, Henner D, Wong WL, Rowland AM, Kotts C, Carver ME, Shepard HM: Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci USA 1992;89:4285–4289.
- Cobleigh MA, Vogel CL, Triapthy D, Robert NJ, Scholl, Fehrenbacher L, Wolter JM, Paton V, Shak S, Lieberman, Slamon DJ: 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 1999;17:2639–2648.
- Cook-Bruns N: Retrospective analysis of the safety of Herceptin® immunotherapy in metastatic breast cancer. Oncology 2001;61(suppl 2):58–66.
- Di Fiore PP, Pierce JH, Fleming TP, Hazan R, Ullrich A, King CR, Schlessinger J, Aaronson SA: Overexpression of the human EGF receptor confers an EGF-dependent transformed phenotype to NIH 3T3 cells. Cell 1987a;51:1063–1070.
- Di Fiore PP, Pierce JH, Kraus MH, Seatto O, King CR, Aaronson SA: erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells. Science 1987b;237:178–182.
- Ewer MS, Gibbs HR, Swafford J, Benjamin RS: Cardiotoxicity in patients receiving Trastuzumab (Herceptin): primary toxicity, synergistic or sequential stress, or surveilance artifact? Semin Oncol 1999;26(suppl 12):96–101.
- Hortobagyi GN: Treatment of breast cancer. N Engl J Med 1998;339:974–984.
- Hudziak RM, Schlessinger J, Ullrich A. Increased expression of the putative growth factor receptor p185HER2 causes transformation and tumorigenesis of NIH 3T3 cells. Proc Natl Acad Sci USA 1987;84:7159–7163.
- Landis SH, Murray T, Bolden S, Wingo PA: Cancer statistics, 1999. CA Cancer J Clin 1999;49:8–31.
- Lewis GD, Fiagari I, Fendly B, Wong WL, Carter P, Gormon C, Shepard HM: Differential responses of the human tumor cell lines to anti-p185HER2 monoclonal antibodies. Cancer Immunol Immunother 1993;37:255–263.
- Mass RD, Sanders C, Charlene K, Johnson L, Everett T, Anderson S: The concordance between the clinical trials assay (CTA) and fluorescence in situ hybridization (FISH) in the Herceptin pivotal trials. Proc Am Soc Clin Oncol 2000;19:75A.
- Norton L, Slamon D, Leyland-Jones B, Wolter J, Fleming T, Eiermann W, Baselga J, Mendelsohn J, Bajamonde A, Ash M, Shak S: Overall survival (OS) advantage to simultaneous chemotherapy (Crx) plus the humanized anti-HER2 monoclonal antibody Herceptin (H) in HER2-overexpressing (HER2+) metastatic breast cancer (MBC). Proc Am Soc Clin Oncol 1999;18:127A.
- Osoba D, Burchmore, M, Ash, M, Tripathy D, Vogel C: Health related quality of life (HRQL) of patients with first-line, single-agent, Trastuzumab (Herceptin) for metastatic HER-2 overexpressing breast cancer. Proc Am Soc Clin Oncol 2000;19:436A.
- Pegram MD, Pietras RJ, Slamon DJ: Monoclonal antibody to HER-2/neu gene product potentiates cytotoxicity of carboplatin and doxorubicin in human breast tumor cells. Proc Am Assoc Cancer Res 1992;33:442.
- Pegram MD, Finn RS, Arzoo K, Beryt M, Pietras RJ, Slamon DJ: The effect of HER-2/neu overexpression on chemotherapeutic drug sensitivity in human breast and ovarian cancer cells. Oncogene 1997;15:537–547.
- Pegram MD, Lipton, A, Hayes DF, Weber BL, Baselga JM, Tripathy D, Baly D, Baughman SA, Twaddell T, Glapsy JA, Slamon DJ: Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p18 5HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J Clin Oncol 1998;16:2659–2671.
- Pegram M, Hsu S, Lewis G, Pietras R, Beryt M, Sliwkowski M, Coombs D, Baly D, Kabbinavar F, Slaomn D: Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers. Oncogene 1999;18:2241–2251.
- Shak S: Overview of the trastuzumab (Herceptin) anti-HER2 monoclonal antibody clinical program in HER2-overexpressing metastatic breast cancer. Semin Oncol 1999;26(suppl 12):71–77.
- Slamon D, et al. Leyland-Jones B, Shak S, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Baselga J, Norton L: Addition of HerceptinTM (humanized anti-HER2 antibody) to first line chemotherapy for HER2 overexpressing metastatic breast cancer (HER2+/MBC) markedly increases anticancer activity: a randomized, multinational controlled phase III trial. Proc Am Soc Clin Oncol 1998;17:98A.
- 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: Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001;344:783–792.
- Vogel C, Cobleigh M, Tripathy D, Harris L, Fehrenbacher L, Slamon D, Ash M, Novotny W, Stewart S, Shak S: First-line, non-hormonal, treatment of woman with HER2 overexpressing metastatic breast cancer with Herceptin (Trastuzumab, humanized anti-HER2 antibody). Proc Am Soc Clin Oncol 2000;19:71A.