An open-label clinical trial evaluating safety and pharmacokinetics of two dosing schedules of panitumumab in patients with solid tumors

Clin Colorectal Cancer. 2009 Jan;8(1):29-37. doi: 10.3816/CCC.2009.n.005.

Abstract

Purpose: This study evaluated safety, pharmacokinetics, and efficacy of 2 dose schedules and 2 infusion times of panitumumab in patients with advanced solid malignancies.

Patients and methods: This phase I multicenter, open-label study sequentially enrolled patients with advanced solid tumors refractory to standard therapy, or for which no standard therapy exists, to receive panitumumab 6 mg/kg every 2 weeks or 9 mg/kg every 3 weeks. Patients receiving panitumumab every 2 weeks received either all infusions over 60 minutes or a 60-minute infusion for the first dose followed by 30-minute infusions if the first infusion was well tolerated. Patients in the every-3-week cohort received 60-minute infusions. Safety outcomes included the incidence of adverse events and antipanitumumab antibody formation. Pharmacokinetic properties were determined. Efficacy endpoints included response rate and duration of response.

Results: Eighty-six patients were enrolled; 84 (98%) received panitumumab. Treatment-related adverse events occurred in 90% of patients. Safety profiles were similar between patients receiving 30-minute (n = 20) and 60-minute (n = 43) infusions every 2 weeks and patients receiving panitumumab every 3 weeks (n = 21). Panitumumab exposure at steady state increased dose proportionally, and peak serum concentrations were similar in patients receiving either 30- or 60-minute infusions every 2 weeks. Objective responses were seen in 4 patients (5%) with colon, rectal, esophageal, and bladder cancers.

Conclusion: Similar drug exposures and safety profiles were observed in patients receiving panitumumab 6 mg/kg every 2 weeks with either 30- or 60-minute infusions and antitumor activity was seen in some patients. Exposure increased approximately dose proportionally at steady state.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacokinetics
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Endpoint Determination
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Panitumumab
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Panitumumab