A phase III trial of pemetrexed plus gemcitabine versus gemcitabine in patients with unresectable or metastatic pancreatic cancer

Helmut Oettle, D. Richards, R. K. Ramanathan, J. L. van Laethem, M. Peeters, M. Fuchs, A. Zimmermann, W. John, D. Von Hoff, M. Arning, H. L. Kindler

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286 Scopus citations

Abstract

Background: This randomized phase III study compared the overall survival (OS) of pemetrexed plus gemcitabine (PG) versus standard gemcitabine (G) in patients with advanced pancreatic cancer. Patients and methods: Patients with unresectable locally advanced or metastatic pancreatic cancer and no prior systemic therapy (including 5-fluorouracil as a radiosensitizer) were randomized to receive either 1250 mg/m2 gemcitabine on days 1 and 8 plus pemetrexed 500 mg/m2 after gemcitabine on day 8 (PG arm) of each 21-day cycle, or gemcitabine 1000 mg/m2 on days 1, 8 and 15 of each 28-day cycle (G arm). Results: Five hundred and sixty-five patients with well-balanced baseline characteristics were randomly assigned (283 PG, 282 G). OS was not improved on the PG arm (6.2 months) compared with the G arm (6.3 months) (P = 0.8477). Progression-free survival (3.9 versus 3.3 months; P = 0.1109) and time to treatment failure (3 versus 2.2 months; P = 0.2680) results were similar. Tumor response rate (14.8% versus 7.1%; P = 0.004) was significantly better on the PG arm. Grade 3 or 4 neutropenia (45.1% versus 12.8%), thrombocytopenia (17.9% versus 6.2%), anemia (13.9% versus 2.9%), febrile neutropenia (9.9% versus 0.4%; all P<0.001) and fatigue (15% versus 6.6%; P = 0.002) were significantly more common on the PG arm. Four treatment-related deaths occurred on the PG arm and none in the G arm. Conclusions: Pemetrexed plus gemcitabine therapy did not improve OS. Single-agent gemcitabine remains the standard of care for advanced pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)1639-1645
Number of pages7
JournalAnnals of Oncology
Volume16
Issue number10
DOIs
StatePublished - Oct 2005

Keywords

  • Gemcitabine
  • Pancreatic cancer
  • Pemetrexed
  • Phase III
  • Survival

ASJC Scopus subject areas

  • Hematology
  • Oncology

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    Oettle, H., Richards, D., Ramanathan, R. K., van Laethem, J. L., Peeters, M., Fuchs, M., Zimmermann, A., John, W., Von Hoff, D., Arning, M., & Kindler, H. L. (2005). A phase III trial of pemetrexed plus gemcitabine versus gemcitabine in patients with unresectable or metastatic pancreatic cancer. Annals of Oncology, 16(10), 1639-1645. https://doi.org/10.1093/annonc/mdi309