Effect of Age on Systemic Exposure and Haematological Toxicity of Carboplatin in Advanced Non-Small Cell Lung Cancer Patients
| Autor: | Begoña Porta-Oltra, Joaquim Monteiro, Matilde Merino-Sanjuán, N. Víctor Jiménez-Torres, I. Maestu, D. Almenar |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Pharmacology
education.field_of_study medicine.medical_specialty Chemotherapy business.industry medicine.medical_treatment Population Area under the curve General Medicine Neutropenia Toxicology medicine.disease Gastroenterology Carboplatin Gemcitabine Surgery chemistry.chemical_compound chemistry Internal medicine Toxicity medicine Lung cancer business education medicine.drug |
| Zdroj: | Basic & Clinical Pharmacology & Toxicology. 109:457-464 |
| ISSN: | 1742-7835 |
| DOI: | 10.1111/j.1742-7843.2011.00753.x |
| Popis: | The aim of this study was to evaluate systemic exposure to carboplatin and its haematological toxicity in patients with advanced non-small cell lung cancer both older and younger than 70 years when the target area under the curve (AUC) in elderly patients was reduced by 20%. For this purpose, a population pharmacokinetic model was developed and the haema- tological toxicity of the drug was assessed. A total of 33 patients received carboplatin on day 1 and gemcitabine (1250 mg ⁄ m 2 ) on days 1 and 8. This schedule was repeated every 21 days. The Calvert-Crokcoft-Gault formula was employed to calculate a dose of carboplatin with a target AUC of 5 mg ⁄ min. ⁄ mL in patients under 70 years and 4m g⁄ min. ⁄ mL in patients aged 70 or older. The data of 24 patients were treated for population modelling performed with the NONMEM (University of California, San Francisco, CA, USA) approach. Haematological toxicity was evaluated for all 33 patients enrolled in the study. The carboplatin systemic exposure measured by the AUC (mg ⁄ min. ⁄ mL) was 5.98 (5.45; 6.51) and 5.36 (5.02; 5.69) for the younger patients and older groups, respectively. No significant differences were observed between the two groups with respect to rates of grade 3+ anaemia, neutropenia or thrombocytopenia. In clinical practice, a target AUC of 4 mg ⁄ min. ⁄ mL carboplatin is applied to patients aged 70 and over, but the actual systemic exposure to the drug is higher. This supports a target AUC of 4 mg ⁄ min. ⁄ mL carboplatin for patients older than 70 years when the dose is calculated by means of the Calvert-Crokcoft-Gault formula. Elderly patients with cancer, independently of the anticancer agent they receive, often present medical and physiological changes that require individualization of the treatment to optimize their response in terms of efficacy and toxicity (1,2). Non-small cell lung cancer (NSCLC) accounts for between 80% and 85% of lung cancers, and more than 50% of advanced cases are diagnosed in patients over 65 years of age, with a mean age at diagnosis of 70 years (1). Physiologi- cal changes associated with ageing, such as declining renal function and a decreasing reserve in multiple organ systems, predispose the elderly to the toxic effects of cancer drugs (3). As a consequence of toxicity, the elderly often receive signifi- cantly fewer doses of chemotherapy than younger patients or their treatment must be discontinued, and as a result, an optimal response is not achieved (4). Carboplatin is usually recommended for elderly patients owing to its low non-haematological toxicity and acceptable levels of haematological toxicity (5). Owing to the close relationship between area under the curve (AUC) and parameters of response and ⁄ or toxicity, specifically thrombo- cytopenia, the standard practice for dose individualization of carboplatin is to calculate the dose of the drug for a |
| Databáze: | OpenAIRE |
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