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Gemcitabine, oxaliplatin, and capecitabine (GEMOXEL) compared with gemcitabine alone in metastatic pancreatic cancer: a randomized phase II study

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Abstract

Background

Single-agent gemcitabine (GEM) has been considered for many years as the standard first-line treatment for advanced pancreatic cancer. However, recently, several studies reported encouraging activity and good tolerability for some combination regimens. Considering the apparently non-overlapping toxicity and the proved individual efficacy of GEM, oxaliplatin (l-OHP), and capecitabine (CAP), this randomized phase II study compared the activity and safety of the combination GEM, l-OHP, and CAP (GEMOXEL) versus GEM alone, in patients with metastatic pancreatic cancer.

Materials and methods

The treatment in GEMOXEL arm consisted of GEM 1,000 mg/m2 as a 30-min intravenous infusion on days 1, 8, 15, 22, l-OHP 100 mg/m2 i.v. on day 2, and CAP 1,500 mg/m2/day in two divided doses on days 1–14, every 21 days (one cycle). In both treatment groups, GEM was administered weekly for seven consecutive weeks followed by 1-week rest for the first 8 weeks, and thereafter, GEM was continued on days 1, 8, 15, every 28 days. Chemotherapy was administered until disease progression or unacceptable toxicity.

Results

Sixty-seven patients were enrolled in the study. Thirty-four were randomly assigned to GEMOXEL and 33 to GEM. At 4 months, disease control rate was 79.4 % with GEMOXEL versus 45.4 % with GEM (p = 0.004). The median progression-free survival was 6.8 months (95 % CI 5.3–7.3 months) in GEMOXEL arm and 3.7 months (95 % CI 2.9–4.7 months) in GEM arm (p < 0.001). The median OS was 11.9 months (95 % CI 10.6–12.9 months) in GEMOXEL arm and 7.1 months (95 % CI 5.5–9.1 months) in GEM arm (p < 0.001). Hematologic and non-hematologic toxicity was more severe with combination chemotherapy, yet still tolerable. No grade 4 adverse events were observed with either regimen.

Conclusion

GEMOXEL regimen seemed to be safe and more efficient than the standard therapy with GEM alone in the treatment of metastatic pancreatic cancer.

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Acknowledgments

The authors wish to thank all the members of the local Oncology Group on Gastrointestinal Tumors and the following oncologists and surgeons who substantially contributed to recruit eligible patients and made this study possible: Dr. Franco Papi, Dr Vinno Savelli, General Surgery, University of Siena; Dr. Carmine Andrea Calvanese, Medical Oncology, Salerno; Dr. G. Giusti, USL 10, Pisa, Italy; Dr. G. Vegni, Volterra Hospital; Dr.ssa T. Cerri Vestri, USL Arezzo.

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Authors and Affiliations

  1. Medical Oncology Unit, University of Siena, Viale Bracci 11, 53100, Siena, Italy

    Roberto Petrioli, Giandomenico Roviello & Letizia Laera

  2. Pharmacology Unit, University of Siena, Siena, Italy

    Anna Ida Fiaschi

  3. Surgical Oncology, Surgery and Neurosciences, University of Siena, Siena, Italy

    Daniele Marrelli

  4. Unit of General and Minimally Invasive Surgery, Surgery and Neurosciences, University of Siena, Siena, Italy

    Franco Roviello

  5. Medical Oncology Unit, Policlinico Umberto I Hospital, University of Rome, Rome, Italy

    Edoardo Francini

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  1. Roberto Petrioli
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Correspondence to Roberto Petrioli.

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Petrioli, R., Roviello, G., Fiaschi, A.I. et al. Gemcitabine, oxaliplatin, and capecitabine (GEMOXEL) compared with gemcitabine alone in metastatic pancreatic cancer: a randomized phase II study. Cancer Chemother Pharmacol 75, 683–690 (2015). https://doi.org/10.1007/s00280-015-2683-1

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