A multicenter, open-label, Phase 1 study evaluating the safety and tolerability of pegaspargase in combination with gemcitabine in advanced metastatic solid tumors and lymphoma

Cancer Invest. 2015 May;33(5):172-9. doi: 10.3109/07357907.2015.1019677. Epub 2015 Apr 6.

Abstract

Purpose: To evaluate the maximum tolerated dose, safety profile, pharmacokinetics, and pharmacodynamics of pegaspargase (PEG-ASP) in combination with gemcitabine in patients with advanced metastatic solid tumors and lymphoma.

Methods: We conducted a multicenter, open label, nonrandomized, Phase 1 dose escalation study designed to evaluate up to 10 cohorts of patients with advanced or metastatic solid tumors and lymphoma. Seventeen patients were treated with of PEG-ASP in combination with gemcitabine.

Results: The study was terminated early because the doses for PEG-ASP suggested for de-escalation were predicted not to provide desired sustained asparaginase concentrations based on the analysis of treated patients.

Keywords: Gemcitabine; Lymphoma; Metastatic solid tumors; Pegaspargase; Phase 1.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols
  • Asparaginase / administration & dosage*
  • Asparaginase / antagonists & inhibitors
  • Asparaginase / pharmacokinetics
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Female
  • Gemcitabine
  • Humans
  • Lymphoma / drug therapy*
  • Lymphoma / pathology
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / pharmacokinetics

Substances

  • Deoxycytidine
  • Polyethylene Glycols
  • pegaspargase
  • Asparaginase
  • Gemcitabine