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Pharmacology and therapeutic use of trastuzumab in breast cancer.

Abstract
The development, pharmacology, safety, efficacy, and dosage and administration of trastuzumab are reviewed. The discovery of HER2 gene amplification in up to 30% of women with breast cancer led to the development of trastuzumab, a humanized recombinant monoclonal antibody directed against the HER2-receptor protein on breast cancer cells. In large, multicenter trials of trastuzumab as a single agent or in combination with chemotherapy as first-line or second-line therapy for metastatic breast cancer (MBC), response rates have ranged from 12% to 23% for single-agent trastuzumab and from 25% to 62% for trastuzumab plus chemotherapy. Trastuzumab increased time to disease progression and survival time when administered in combination with chemotherapy. The National Comprehensive Cancer Network guidelines for the treatment of breast cancer now include trastuzumab and paclitaxel as an option for patients with MBC or recurrent breast cancer in which the HER2-receptor protein is overexpressed. Trastuzumab is administered weekly, with an initial i.v. dose of 4 mg/kg followed by weekly doses of 2 mg/kg. Most clinical trials continued treatment until disease progression occurred. Adverse effects include infusion-related reactions manifested by fever and chills, exacerbation of chemotherapy-induced gastrointestinal toxicity and myelosuppression, and cardiotoxicity. Trastuzumab, either as a single agent or in combination with chemotherapy, can be an effective therapeutic option for MBC patients who overexpress the HER2-receptor protein and has changed the standard of care.
AuthorsI Treish, R Schwartz, C Lindley
JournalAmerican journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists (Am J Health Syst Pharm) Vol. 57 Issue 22 Pg. 2063-76; quiz 2077-9 (Nov 15 2000) ISSN: 1079-2082 [Print] England
PMID11098307 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Trastuzumab
Topics
  • Antibodies, Monoclonal (adverse effects, pharmacology, therapeutic use)
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents (therapeutic use)
  • Breast Neoplasms (drug therapy, genetics, psychology)
  • Clinical Trials as Topic
  • Female
  • Genes, erbB-2
  • Humans
  • Quality of Life
  • Trastuzumab

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