title: Lack of pharmacokinetic drug-drug interaction between ramucirumab and paclitaxel in a phase II study of patients with advanced malignant solid tumors.
abstract: OBJECTIVE
  The objective of this phase II study was to evaluate pharmacokinetic interaction potential between ramucirumab and paclitaxel in patients with advanced cancer.
  
  
  METHODS
  This study was designed to assess 2-way pharmacokinetic drug-drug interactions between ramucirumab and paclitaxel. Twenty-four patients participated in Part A, which consisted of a 2-week monotherapy period in which paclitaxel 80 mg/m(2) was administered on day 1, followed by a 4-week cycle of combination treatment with ramucirumab (8 mg/kg on days 1 and 15; paclitaxel on days 1, 8, and 15). Patients could continue to receive combination therapy with ramucirumab and paclitaxel. In 16 patients in Part B, ramucirumab monotherapy was administered on day 1 of a 3-week cycle. Patients could continue to receive ramucirumab monotherapy or combination therapy with paclitaxel.
  
  
  RESULTS
  Concomitant administration of ramucirumab had no effect on pharmacokinetics of paclitaxel, with ratios of geometric least squares (LS) means (with ramucirumab vs. alone) of 1.09 (90 % confidence interval [CI] 0.93, 1.29) for AUC(0-∞) and 0.97 (90 % CI 0.83, 1.13) for C max. In addition, similar ramucirumab pharmacokinetic characteristics were observed with or without paclitaxel administration. The ratios of geometric LS means of AUC(0-∞) and C max of ramucirumab (with paclitaxel vs. alone) were 1.00 (90 % CI 0.84, 1.19) for AUC(0-∞) and 1.07 (90 % CI 0.93, 1.24) for C max, respectively.
  
  
  CONCLUSIONS
  Concomitant paclitaxel administration is unlikely to affect the pharmacokinetics of ramucirumab, and vice versa. The incidence and severity of adverse events were consistent with the known safety profiles of paclitaxel and ramucirumab.
authors.affiliation: University of Washington, Seattle Cancer Care Alliance, MSG4-940, 825 Eastlake Ave E, Box 358081, Seattle, WA, 98109, USA. lchow@seattlecca.org.
authors.forename: Laura Q M
authors.initials: LQ
authors.lastname: Chow
authors.affiliation: University of Michigan, Ann Arbor, MI, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Smith
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
authors.forename: Antoinette R
authors.initials: AR
authors.lastname: Tan
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: Crystal S
authors.initials: CS
authors.lastname: Denlinger
authors.affiliation: Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Ding
authors.initials: D
authors.lastname: Wang
authors.affiliation: Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Dale R
authors.initials: DR
authors.lastname: Shepard
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Chaudhary
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Eli Lilly and Company, Bridgewater, NJ, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D004347:Drug Interactions; D005260:Female; D006801:Humans; D015994:Incidence; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D055815:Young Adult; D000096662:Ramucirumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D017239:Paclitaxel; D000096662:Ramucirumab
keywords: Cancer; Drug–drug interactions; Paclitaxel; Pharmacokinetics; Ramucirumab