title: A phase I pharmacokinetic study of bexarotene with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer (NSCLC).
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Institute for Drug Development, Cancer Therapy and Research Center at The University of Texas Health Science Center, San Antonio, TX, USA.
authors: Jordi
authors: J
authors: Rodon
authors: Charlotte D
authors: CD
authors: Jacobs
authors: Quincy
authors: Q
authors: Chu
authors: Eric K
authors: EK
authors: Rowinsky
authors: Arturo
authors: A
authors: Lopez-Anaya
authors: Chris H
authors: CH
authors: Takimoto
authors: Heather A
authors: HA
authors: Wakelee
mesh_terms: D000284:Administration, Oral; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077610:Bexarotene; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D047488:Retinoid X Receptors / Q000819:agonists; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000960:Hypolipidemic Agents; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes; D000077610:Bexarotene; D016190:Carboplatin; D017239:Paclitaxel