Analysis of dermatologic events in patients with cancer treated with lapatinib

• Published in: Breast cancer research and treatment Vol. 114; no. 3; pp. 485 - 493
• Main Authors: Lacouture, M. E, Laabs, S. M, Koehler, M, Sweetman, R. W, Preston, A. J, Di Leo, A, Gomez, H. L, Salazar, V. M, Byrne, J. A, Koch, K. M, Blackwell, K. L
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01.04.2009; Springer US; Springer; Springer Nature B.V
• Subjects: Acneiform; Adult; Adverse events; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; Breast cancer; breast neoplasms; Cancer research; Cancer therapies; Capecitabine; Chemotherapy; Clinical Trial; Clinical Trials as Topic; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; EGFR; Exanthema - etiology; Female; Fluorouracil - administration & dosage; Fluorouracil - analogs & derivatives; Gynecology. Andrology. Obstetrics; Humans; Inhibitor drugs; Lapatinib; Male; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Metastatic rash; Middle Aged; Neoplasms - complications; Neoplasms - drug therapy; Oncology; Paclitaxel - administration & dosage; Pharmacology. Drug treatments; Quinazolines - administration & dosage; Quinazolines - adverse effects; Receptor, Epidermal Growth Factor - metabolism; Side effects; Skin diseases; Skin Diseases - etiology; Toxicity: skin, dermoskeleton; Treatment Outcome; Tumors; Tyrosine kinase inhibitor; Adverse events; Tyrosine kinase inhibitor; Acneiform; Breast cancer; Lapatinib; EGFR; Metastatic rash; Antineoplastic agent; Skin disease; Breast disease; Toxicity; Metastasis; Epidermal growth factor receptor; Secondary effect; Advanced stage; Protein-tyrosine kinase; Human; Enzyme; Transferases; Acneiform .Adverse events; Enzyme inhibitor; Patient; Malignant tumor; Mammary gland diseases; Treatment; Analysis; Erythema; Cancer
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-008-0020-7

Purpose Dermatologic events (DEs) in patients with cancer treated with lapatinib, a small-molecule dual tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR [ErbB1]) and HER2 (ErbB2), were characterized. Patients and methods Nine clinical trials of metastatic cancer were included in this analysis. Lapatinib was administered at doses ranging from 1000 to 1500 mg/day as monotherapy (n = 928) or in combination with paclitaxel or capecitabine (n = 491). Patients not treated with lapatinib comprised the control group. Dermatologic events included hand-foot syndrome, rash, hair disorder, dry skin, pruritus/urticaria, skin disorder, skin infection, and nail disorder; DEs were characterized based on type, time to onset, severity, duration, and required interventions. Results Fifty-eight percent of patients treated with lapatinib monotherapy, 74% treated with lapatinib plus paclitaxel or capecitabine, and 53% in the control group developed DEs. Among patients receiving lapatinib monotherapy, 55% experienced grade 1/2 DEs, 3% had grade 3 DEs, and no grade 4 DEs were observed. The most common DE was rash (43%); all other events occurred in <=8% of patients. Most DEs developed between days 1 and 14 of starting treatment, with a median duration of 29 days. Three percent of DEs led to lapatinib dose reduction, 7% resulted in dose interruption, and 1% led to drug discontinuation. Conclusions Most DEs in lapatinib-treated patients present early, are mild to moderate in severity, and infrequently require dose modification or treatment interruption. Lapatinib-associated DEs appear to differ clinically from those associated with EGFR TKIs in both frequency and severity.