Relationship between plasma pazopanib concentration and incidence of adverse events in renal cell carcinoma
| العنوان: | Relationship between plasma pazopanib concentration and incidence of adverse events in renal cell carcinoma |
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| المؤلفون: | B. Suttle, Lini Pandite, Thomas E. Hutson, F. Mehmud, Rafael G. Amado, H. A. Ball, Y. Lin |
| المصدر: | Journal of Clinical Oncology. 29:345-345 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Oncology, Cancer Research, medicine.medical_specialty, biology, business.industry, Incidence (epidemiology), VEGF receptors, Pharmacology, medicine.disease, Angiogenesis inhibitor, Pazopanib, Renal cell carcinoma, Internal medicine, biology.protein, Medicine, Cell cancer, business, Adverse effect, Platelet-derived growth factor receptor, medicine.drug |
| الوصف: | 345 Background: Pazopanib (P), an oral angiogenesis inhibitor targeting VEGFR, PDGFR, and c-Kit, is approved by the US FDA for the treatment of advanced renal cell cancer (mRCC). Exploratory analyses of data from a Ph II mRCC study (Hutson T, J Clin Oncol. 27, 2009:1) indicated that 70% of patients (pt) receiving 800mg once daily had a week (wk) 4 plasma P trough (Cmin) >20.6μ g/mL that is associated with improved efficacy (Suttle B, J Clin Oncol. 28, 2010:S3048). In this further analysis of the dataset, we investigated the relation between plasma P concentrations at wk 4 and clinically important adverse events (AE) reported within the first 12 wks of treatment. Methods: The % of patients with hypertension (defined as ≥ 15mmHg - baseline on 3 occasions)- a recognized PD marker for this class of agents- or other AEs (CTC grades), occurring during the first 12 wks of treatment were calculated by wk4 Cmin quartiles (Q1-Q4: median and range). Results: P concentrations at 4 wks and AE data were available for 205 out of 225 pts. The incidence of hypertension was 58% in Q1, increasing with concentration to 78% at Q4. The incidence of diarrhea, hair color change, ALT increase, HFS (marked increase), and stomatitis were concentration-dependent, with ≥ 2 fold increase from Q1 to Q4. The incidence of nausea, fatigue, vomiting, dysgeusia, and rash were variable or displayed a flat relationship with Cmin. Conclusions: The incidence of some AEs, such as diarrhea, ALT, HFS (marked relation), and stomatitis increased with plasma Cmin while others did not. We suggest that concentration-dependent AEs are more likely to respond to P dose reduction and as such, provides support for development of a dose optimization strategy. [Table: see text] [Table: see text] |
| تدمد: | 1527-7755 0732-183X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::d5e176ab45dbeab4a1f8b14db04a7375 https://doi.org/10.1200/jco.2011.29.7_suppl.345 |
| رقم الأكسشن: | edsair.doi...........d5e176ab45dbeab4a1f8b14db04a7375 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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