A phase I pharmacokinetic study of bexarotene with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer (NSCLC)
| Autor: | Eric K. Rowinsky, Chris H. Takimoto, Charlotte Jacobs, Arturo Lopez-Anaya, Quincy Chu, Heather A. Wakelee, J. Rodon |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Male
Cancer Research Lung Neoplasms Paclitaxel Tetrahydronaphthalenes medicine.medical_treatment Administration Oral non-small cell lung cancer (NSCLC) Pharmacology Toxicology Drug Administration Schedule Carboplatin chemistry.chemical_compound Pharmacokinetics Carcinoma Non-Small-Cell Lung Antineoplastic Combined Chemotherapy Protocols medicine Humans Drug Interactions Pharmacology (medical) Infusions Intravenous Hypolipidemic Agents Bexarotene Chemotherapy Dose-Response Relationship Drug business.industry Middle Aged medicine.disease Chemotherapy regimen Retinoid X Receptors Oncology chemistry Female business medicine.drug Blood sampling |
| Zdroj: | Cancer Chemotherapy and Pharmacology. 69:825-834 |
| ISSN: | 1432-0843 0344-5704 |
| Popis: | Preclinical data suggest that the synthetic retinoid bexarotene may be an effective chemopreventive agent and that it may act synergistically in combination with platinum-based chemotherapy. The primary objective of this study was to determine whether repeated doses of bexarotene capsules affect pharmacokinetic parameters of paclitaxel or carboplatin in patients with advanced non-small cell lung cancer.Patients received treatment with paclitaxel (200 mg/m(2)) and carboplatin to provide a target AUC of 6 mg min/mL (day 1) every 3 weeks. Continuous oral bexarotene therapy (400 mg/m(2)/day) was initiated on Day 4, and patients started lipid-lowering therapy prior to beginning chemotherapy. Blood sampling to characterize the pharmacokinetic profiles of the chemotherapeutic agents with or without bexarotene was performed during cycle 1 (without concomitant bexarotene) and during cycle 2 (with concomitant bexarotene).An analysis of drug concentration data from 16 patients indicated that bexarotene did not affect the pharmacokinetics of paclitaxel, free carboplatin, or total carboplatin concentrations. However, both maximal plasma concentrations and total exposure of bexarotene increased by 80% in the presence of paclitaxel-carboplatin by an, as of yet, unexplained mechanism. The toxicities observed resembled those of either the chemotherapy regimen or bexarotene alone, and there was no evidence for an enhancement of any drug-related toxicity with the combined treatment.The administration of bexarotene, paclitaxel, and carboplatin is feasible and safe; however, the increased bexarotene plasma concentrations and exposure warrant further investigation if this combination is to be utilized clinically. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink