A Phase II, open-label, randomised study to assess the efficacy and safety of the MEK1/2 inhibitor AZD6244 (ARRY-142886) versus capecitabine monotherapy in patients with colorectal cancer who have failed one or two prior chemotherapeutic regimens

Invest New Drugs. 2011 Oct;29(5):1021-8. doi: 10.1007/s10637-010-9392-8. Epub 2010 Feb 2.


Objectives: To assess the efficacy and safety of the MEK1/2 inhibitor AZD6244 (ARRY-142886) in patients with metastatic colorectal cancer who had failed one or two previous chemotherapeutic regimens that included oxaliplatin and/or irinotecan.

Methods: This was a Phase II, multicentre, open-label, randomised, two-arm, parallel-group study comparing AZD6244 with capecitabine monotherapy. Patients received either 100 mg twice daily oral AZD6244 free-base suspension every day or 1,250 mg/m(2) twice daily oral capecitabine, for 2 weeks, followed by a 1-week rest period, in 3-weekly cycles. The primary endpoint was the number of patients experiencing disease progression events.

Results: Sixty-nine patients were randomised in the study (34 and 35 patients in the AZD6244 and capecitabine groups, respectively). Disease progression events were experienced by 28 patients (~80%) in both the AZD6244 and capecitabine treatment groups. Median progression-free survival was 81 days and 88 days in the AZD6244 and capecitabine groups, respectively. Ten patients in the AZD6244 treatment arm had a best response of stable disease. For capecitabine, best response was a partial response in one patient, with stable disease in a further 15 patients. The most frequently observed adverse events reported with AZD6244 were acneiform dermatitis, diarrhoea, asthenia and peripheral oedema, compared with hand-foot syndrome, diarrhoea, nausea and abdominal pain with capecitabine.

Conclusions: AZD6244 showed similar efficacy to capecitabine in terms of the number of patients with a disease progression event and of progression-free survival. AZD6244 is currently undergoing evaluation in Phase II trials in combination with other chemotherapeutic agents.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / adverse effects*
  • Benzimidazoles / therapeutic use*
  • Capecitabine
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / enzymology
  • Demography
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Disease Progression
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / analogs & derivatives*
  • Fluorouracil / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Proportional Hazards Models
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Treatment Failure


  • AZD 6244
  • Antineoplastic Agents
  • Benzimidazoles
  • Protein Kinase Inhibitors
  • Deoxycytidine
  • Capecitabine
  • Mitogen-Activated Protein Kinase Kinases
  • Fluorouracil