Analysis of dermatologic events in patients with cancer treated with lapatinib.
ABSTRACT 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.
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.
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 <or=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.
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.
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ABSTRACT: The discovery of the intricate intracellular signaling networks that regulate normal cellular proliferation and survival but can also drive the oncogenic process when aberrantly activated has led to the emergence of targeted agents in oncology. The introduction of such agents has resulted in improved survival and more tolerable treatments, reducing systemic toxicities such as myelosuppression. Nevertheless, it has become evident that these agents are associated with a wide spectrum of dermatologic toxicities that often manifest in cosmetically sensitive areas and may affect the majority of patients. Associated pain and pruritus can negatively impact quality of life, resulting in dose modification or treatment interruptions that interfere with potentially life-prolonging therapy. Extensive efforts throughout the past decade have concentrated on describing the clinicohistopathologic characteristics, elucidating the underlying mechanisms, and investigating potential management strategies. Currently, however, proposed treatment guidelines arise from expert opinions, anecdotal evidence, and few data from clinical trials. This article reviews the spectrum of dermatologic toxicities associated with a variety of targeted agents used alone or in combination with other modalities, delineating their clinical presentation, underlying mechanisms, and management options.The journal of supportive oncology 8(4):149-61.
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ABSTRACT: Deals with the production and the corrective maintenance planning control problem for failure-prone manufacturing systems. For a one machine one part type system, a suboptimal control policy is proposed and the required control parameters are determined using stochastic optimization techniques. Numerical examples are presented to show the usefulness of the proposed results.Decision and Control, 2002, Proceedings of the 41st IEEE Conference on; 01/2003
- Value in Health 05/2003; 6(3):261-261. DOI:10.1016/S1098-3015(10)64004-1 · 2.89 Impact Factor