A phase I pharmacokinetic study of bexarotene with vinorelbine and cisplatin in patients with advanced non-small-cell lung cancer (NSCLC)
| Autor: | Arturo Lopez-Anaya, Petr Zatloukal, Charlotte Jacobs, Gary Middleton, Heather A. Wakelee, Desiree Hao, D. Dunlop, Natasha B. Leighl, Rodryg Ramlau |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Agonist Oncology Cancer Research medicine.medical_specialty Lung Neoplasms Tetrahydronaphthalenes medicine.drug_class Administration Oral non-small cell lung cancer (NSCLC) Retinoid X receptor Vinblastine Toxicology Vinorelbine Drug Administration Schedule Pharmacokinetics Carcinoma Non-Small-Cell Lung Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Drug Interactions Pharmacology (medical) Infusions Intravenous Aged Hypolipidemic Agents Pharmacology Cisplatin Bexarotene Dose-Response Relationship Drug business.industry Middle Aged medicine.disease Retinoid X Receptors Female business medicine.drug |
| Zdroj: | Cancer Chemotherapy and Pharmacology. 69:815-824 |
| ISSN: | 1432-0843 0344-5704 |
| DOI: | 10.1007/s00280-011-1771-0 |
| Popis: | This is a phase I study of the retinoid X receptor agonist bexarotene (Targretin(®)) in combination with the chemotherapeutic drugs cisplatin and vinorelbine and lipid-lowering therapy. This study looked for pharmacokinetic (PK) interactions between the agents in parallel with a phase III study of the combination.Patients (n = 26) with advanced-stage non-small-cell lung cancer received intravenous cisplatin 100 mg/m(2) on day 1 and at 4-week intervals plus intravenous vinorelbine 25 mg/m(2) weekly. Continuous oral bexarotene therapy (400 mg/m(2)/day) was initiated at day 4. Lipid-lowering therapy was initiated in all patients due to hypertriglyceridemia associated with bexarotene use. PK profiles of the chemotherapeutic agents were obtained on day 1 (without bexarotene) and during cycles 2-4 (with bexarotene). Vinorelbine (n = 18) and free cisplatin (n = 17) PK parameters in evaluable patients were determined using non-compartmental methods.Mean vinorelbine and free cisplatin clearance and dose-corrected AUC values with bexarotene were within 20% of respective values without concomitant bexarotene. Bexarotene levels did not vary with or without co-administration of the chemotherapeutic agents. There was no evidence of increased toxicity when bexarotene was co-administered with the chemotherapeutic agents.Bexarotene does not substantially affect vinorelbine or cisplatin PK, and the combination is well tolerated. The results are consistent with the mechanisms of elimination of vinorelbine (high metabolic clearance) and cisplatin (non-enzymatic and renal elimination). |
| Databáze: | OpenAIRE |
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