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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

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An Erratum to this article was published on 26 July 2011

Summary

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/m2 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.

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Acknowledgements

We thank Dr Sally Humphries, from MediTech Media, who provided medical writing support and Helen Williams, from iMed Comms, who provided editorial assistance funded by AstraZeneca. Dr Gillian Pover is no longer an employee of AstraZeneca.

Funding

This was a phase II signal-searching study funded by AstraZeneca.

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Authors and Affiliations

  1. Department of Oncology, St. László Hospital, Gyáli út 5–7, 1097, Budapest, Hungary

    György Bodoky

  2. National Oncology Centre, Clinic of Chemotherapy, 5 Plovdivsko pole St., 1756, Sofia, Bulgaria

    Constanta Timcheva

  3. Sarah Cannon Research Institute, (SCRI), 250 25th Avenue North, Suite 110, Nashville, TN, 37203, USA

    David Robert Spigel

  4. St. Joseph Mercy Hospital Cancer Care Center, 5301 East Huron River Drive, P.O. Box 995, Ann Arbor, MI, 48106–0995, USA

    Phillip Joseph La Stella

  5. Day Hospital Department-Medical Oncology, Oncological Institute I Chiricuta, Republicii 34–36 str, Cluj-Napoca, 40015, Romania

    Tudor Eliade Ciuleanu

  6. AstraZeneca, Alderley Park, UK

    G. Pover

  7. Austin Heath, Heidelberg, VIC, 3084, Australia

    N. C. Tebbutt

Authors
  1. György Bodoky
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  2. Constanta Timcheva
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  3. David Robert Spigel
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  4. Phillip Joseph La Stella
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  5. Tudor Eliade Ciuleanu
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  6. G. Pover
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  7. N. C. Tebbutt
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Correspondence to György Bodoky.

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Bodoky, G., Timcheva, C., Spigel, D.R. et al. 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 30, 1216–1223 (2012). https://doi.org/10.1007/s10637-011-9687-4

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  • DOI: https://doi.org/10.1007/s10637-011-9687-4

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