A phase II open-label randomized study to assess the efficacy and safety of selumetinib (AZD6244 [ARRY-142886]) versus capecitabine in patients with advanced or metastatic pancreatic cancer who have failed first-line gemcitabine therapy

Invest New Drugs. 2012 Jun;30(3):1216-23. doi: 10.1007/s10637-011-9687-4. Epub 2011 May 19.

Abstract

Selumetinib is a potent, selective MEK inhibitor with efficacy in several tumor models. This study compared selumetinib with capecitabine in patients with advanced or metastatic pancreatic cancer who had been pretreated with a gemcitabine-based regimen. In this randomized, multicenter phase II study (NCT00372944), patients received either 100 mg oral selumetinib twice daily or 1,250 mg/m(2) oral capecitabine twice daily for 2 weeks followed by a 1-week break, given in 3-weekly cycles. The primary endpoint was overall survival. In all 70 patients were randomized. The median survival was 5.4 months in the selumetinib group and 5.0 months in the capecitabine group (hazard ratio 1.03; two-sided 80% confidence interval = 0.68,1.57; P = 0.92). Disease progression events occurred in 84% and 88% of patients in the selumetinib and capecitabine treatment groups, respectively. Gastrointestinal adverse events (nausea, vomiting and diarrhea) were commonly observed in both treatment groups. Other frequently reported adverse events were acneiform dermatitis and peripheral edema with selumetinib, and palmar-plantar erythrodysaesthesia with capecitabine. There was no statistically significant difference in overall survival between selumetinib and capecitabine as second-line treatment in patients with advanced pancreatic cancer. Selumetinib was well tolerated with a manageable safety profile.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Benzimidazoles / therapeutic use*
  • Capecitabine
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Drug Resistance, Neoplasm
  • Female
  • Fluorouracil / analogs & derivatives*
  • Fluorouracil / therapeutic use
  • Humans
  • MAP Kinase Kinase Kinases / antagonists & inhibitors
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Protein Kinase Inhibitors / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • AZD 6244
  • Antimetabolites, Antineoplastic
  • Benzimidazoles
  • Protein Kinase Inhibitors
  • Deoxycytidine
  • Capecitabine
  • gemcitabine
  • MAP Kinase Kinase Kinases
  • Fluorouracil