A phase I study of lapatinib with whole brain radiotherapy in patients with Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer brain metastases

• Published in: Breast cancer research and treatment 2013-11, Vol.142 (2), p.405-414
• Main Authors: Lin, Nancy U., Freedman, Rachel A., Ramakrishna, Naren, Younger, Jerry, Storniolo, Anna Maria, Bellon, Jennifer R., Come, Steven E., Gelman, Rebecca S., Harris, Gordon J., Henderson, Mark A., MacDonald, Shannon M., Mahadevan, Anand, Eisenberg, Emily, Ligibel, Jennifer A., Mayer, Erica L., Moy, Beverly, Eichler, April F., Winer, Eric P.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antimitotic agents; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Brain; Brain cancer; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Brain Neoplasms - radiotherapy; Brain Neoplasms - secondary; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Breast Neoplasms - radiotherapy; Cancer research; Care and treatment; Clinical Trial; Diarrhea; Embolism; Epidermal growth factor; ErbB-2 protein; Exanthema; Female; Gynecology. Andrology. Obstetrics; Humans; Hypoxia; Inhibitor drugs; Mammary gland diseases; Medical research; Medical sciences; Medicine; Medicine & Public Health; Medicine, Experimental; Metastases; Metastasis; Middle Aged; Mucositis; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neurology; Oncology; Patients; Pulmonary embolism; Quality of Life; Quinazolines - administration & dosage; Quinazolines - adverse effects; Quinazolines - therapeutic use; Radiation therapy; Radiotherapy; Receptor, ErbB-2 - metabolism; Toxicity; Trastuzumab; Treatment Outcome; Tumors; Tumors of the nervous system. Phacomatoses
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-013-2754-0

Brain metastases are common in patients with advanced, Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer. We evaluated the maximum tolerated dose (MTD) and feasibility of lapatinib given concurrently with whole brain radiotherapy (WBRT). Eligible patients had (HER2)-positive breast cancer and ≥1 brain metastasis. Patients received lapatinib 750 mg twice on day one followed by 1000, 1250, or 1500 mg once daily. WBRT (37.5 Gy, 15 fractions) began 1–8 days after starting lapatinib. Lapatinib was continued through WBRT. Following WBRT, patients received trastuzumab 2 mg/kg weekly and lapatinib 1000 mg once daily. The regimen would be considered feasible if