Phase II study of pemetrexed in patients pretreated with an anthracycline, a taxane, and capecitabine for advanced breast cancer

Joyce A. O'Shaughnessy, Romnee S. Clark, Joanne L. Blum, Robert G. Mennel, David Snyder, Zhishen Ye, Astra M. Liepa, Allen S. Melemed, Denise A. Yardley

Research output: Contribution to journalArticle

45 Scopus citations


Background: This phase II study evaluated the efficacy, safety, health outcomes of pemetrexed treatment in heavily pretreated patients with advanced breast cancer. Patients and methods: Women with metastatic breast cancer, Karnofsky performance status ≥ 70, and previous with ≥ 3 regimens containing apthracyclines, taxanes, and capecitabine were eligible. Pemetrexed 500 mg/m2 intravenous infusion was administered on day 1 of a 21-day treatment cycle. Results: Eighty patients were enrolled, and 60 received concurrent folic acid and vitamin B12 supplements per protocol amendment to minimize possible pemetrexed-related toxicity. The median numbers of cycles delivered were 3 for vitamin-supplemented patients and 2 for non-vitamin-supplemented patients. Regardless of vitamin supplementation, the overall response rate was 8% (95% CI, 3%-16.6%), stable disease was exhibited in 36% of patients, median time to disease progression was 2.9 months, and median survival was 8.2 months. Improvements in patient-reported symptoms ranged from 16.2% for pain intensity to 32.1% for nausea. Major grade 3/4 toxicities were hematologic, with grade 4 neutropenia in 10% of patients and grade 3 toxicities consisting primarily of neutropenia (29%) and luekopenia (21%). There were no clear trends of the effect of supplementation on toxicity. Conclusion: Pemetrexed has modest antitumor activity and is well tolerated in heavily pretreated patients with breast cancer. Further evaluation of this multitargeted antifolate in advanced breast cancer is warranted.

Original languageEnglish (US)
Pages (from-to)143-149
Number of pages7
JournalClinical breast cancer
Issue number2
StatePublished - Jun 2005



  • Multitargeted antifolates
  • Toxicity
  • Vitamin suplementation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

O'Shaughnessy, J. A., Clark, R. S., Blum, J. L., Mennel, R. G., Snyder, D., Ye, Z., Liepa, A. M., Melemed, A. S., & Yardley, D. A. (2005). Phase II study of pemetrexed in patients pretreated with an anthracycline, a taxane, and capecitabine for advanced breast cancer. Clinical breast cancer, 6(2), 143-149.