Phase I study of nonpegylated liposomal doxorubicin plus trastuzumab in patients with HER2-positive breast cancer Journal Article
| Authors: | Theodoulou, M.; Batist, G.; Campos, S.; Winer, E.; Welles, L.; Hudis, C. |
| Article Title: | Phase I study of nonpegylated liposomal doxorubicin plus trastuzumab in patients with HER2-positive breast cancer |
| Abstract: | Background: This was an open-label, nonrandomized, multicenter, 2-stage phase I trial of safety and preliminary efficacy of nonpegylated liposomal doxorubicin (NLD) in combination with trastuzumab in advanced breast cancer, with emphasis on cardiac toxicity. Patients and Methods: Forty patients (median age, 48 years; range, 30-74 years) with HER2/neu 2+ or 3+ tumors (by immunohistochemistry) were recruited December 1999 to November 2002. Patients were eligible if they received ≤ 1 previous trastuzumab regimen, ≤ 2 cytotoxic regimens for advanced breast cancer, and lifetime cumulative anthracycline doses ≤ 240 mg/m<sup>2</sup>. The study regimen comprised NLD 60 mg/m<sup>2</sup> every 3 weeks and trastuzumab loading dose 4 mg/kg followed by 2 mg/kg weekly. Treatment cycles lasted 21 days. Clinical cardiac assessments were performed with multigated acquisition scans every 2 cycles. Patients were evaluated for cardiac toxicity after receiving ≥ 1 cycle. Cardiac safety was assessed after completing ≥ 4 full treatment cycles. Results: Thirty out of 40 patients (75%) received ≥ 4 treatment cycles and were evaluable for cardiac safety. Five patients (13%), 4 who were doxorubicin pretreated, developed left ventricular ejection fraction reductions to < 50%, and 2 (5%) of these patients experienced clinical cardiac toxicity. Fifty percent of the patients had objective tumor responses; median progression-free survival was approximately 21 weeks. Twenty-six patients (65%) had grade 3/4 neutropenia; 2 patients experienced febrile neutropenia. Conclusion: Nonpegylated liposomal doxorubicin plus trastuzumab is active in HER2-positive patients with advanced breast cancer and is associated with a lower risk of cardiac toxicity than conventional doxorubicin plus trastuzumab. |
| Keywords: | immunohistochemistry; adult; cancer chemotherapy; cancer survival; clinical article; treatment outcome; treatment response; aged; middle aged; survival rate; clinical trial; fatigue; neutropenia; doxorubicin; advanced cancer; cancer combination chemotherapy; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; multimodality cancer therapy; side effect; treatment duration; cancer patient; cancer staging; antineoplastic agent; neoplasm staging; metabolism; progression free survival; controlled clinical trial; multiple cycle treatment; breast cancer; mucosa inflammation; nausea; randomized controlled trial; stomatitis; vomiting; antineoplastic combined chemotherapy protocols; epidermal growth factor receptor 2; cyclophosphamide; deep vein thrombosis; pathology; breast neoplasms; monoclonal antibody; asthenia; febrile neutropenia; loading drug dose; antibodies, monoclonal; multicenter study; prophylaxis; breast tumor; open study; receptor, erbb-2; hormonal therapy; phase 1 clinical trial; trastuzumab; bone marrow transplantation; drug dose regimen; heart left ventricle ejection fraction; alopecia; granulocyte colony stimulating factor; congestive heart failure; cardiac toxicity; left ventricular ejection fraction; oncogene neu |
| Journal Title: | Clinical Breast Cancer |
| Volume: | 9 |
| Issue: | 2 |
| ISSN: | 1526-8209 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2009-05-01 |
| Start Page: | 101 |
| End Page: | 107 |
| Language: | English |
| DOI: | 10.3816/CBC.2009.n.019 |
| PUBMED: | 19433391 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 30 November 2010" - "CODEN: CBCLB" - "Source: Scopus" |
