Phase II Study of Celecoxib and Trastuzumab in Metastatic Breast Cancer Patients Who Have Progressed after Prior Trastuzumab-Based Treatments

• Published in: Clinical cancer research Vol. 10; no. 12; pp. 4062 - 4067
• Main Authors: DANG, Chau T, DANNENBERG, Andrew J, HUDIS, Clifford A, SUBBARAMAIAH, Kotha, DICKLER, Maura N, MOASSER, Mark M, SEIDMAN, Andrew D, D'ANDREA, Gabriella M, THEODOULOU, Maria, PANAGEAS, Katherine S, NORTON, Larry
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.06.2004
• Subjects: Adult; Aged; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Celecoxib; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - therapeutic use; Female; Humans; In Situ Hybridization, Fluorescence; Isoenzymes - metabolism; Medical sciences; Membrane Proteins; Middle Aged; Neoplasm Metastasis; Pharmacology. Drug treatments; Prostaglandin-Endoperoxide Synthases - metabolism; Pyrazoles - therapeutic use; Receptor, ErbB-2 - chemistry; Receptor, ErbB-2 - metabolism; Sulfonamides - therapeutic use; Time Factors; Trastuzumab; Tumors; Human; Prostaglandin-endoperoxide synthase; Enzyme; Enzyme inhibitor; Cyclooxygenase 2 inhibitor; Breast cancer; Monoclonal antibody; Celecoxib; Metastasis; Malignant tumor; Non steroidal antiinflammatory agent; Immunomodulator; Mammary gland diseases; Treatment; Phase II trial; Advanced stage; Metastatic; Oxidoreductases; Mammary gland; Trastuzumab
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-03-0463

Purpose: Preclinical studies demonstrate a link between overexpression of HER-2/ neu and cyclooxygenase-2 (COX-2) activity. To explore the possibility that COX-2 is a therapeutic target, we conducted a phase II study of celecoxib, a selective COX-2 inhibitor, and trastuzumab in patients with HER-2/ neu -overexpressing metastatic breast cancer that had progressed while receiving trastuzumab. Experimental Design: Eligible patients had bi-dimensionally measurable or evaluable HER-2/ neu -overexpressing metastatic breast cancer. HER-2/ neu overexpression, defined as 2+ or 3+ by the HercepTest, was required. Patients had to have progressed despite prior trastuzumab-based therapy. Treatment consisted of celecoxib (400 mg twice daily) and trastuzumab. Results: Twelve patients were enrolled (42% status post 1 regimen for metastatic disease 58% status post > 2 prior regimens (range of 2–6). Eleven patients were evaluable. There were no responses. Median duration of treatment was 9 weeks. One patient had stable disease at 3 months but progressed at 6 months. A second patient stopped treatment at 3 months because of unresolved grade 2 rash, felt to be related to celecoxib. Toxicities were generally grade 1 or 2. One patient (8%) experienced grade 3 toxicity (abdominal pain). Conclusions: Celecoxib combined with trastuzumab is well tolerated. However, this combination in patients with HER2/neu-overexpressing, trastuzumab-refractory disease, was not active.