Abstract
Purpose
Pemetrexed (PEM) is a novel folate antimetabolite which inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. This phase II study was designed to assess the efficacy of Gemcitabine (GEM) and PEM given in a novel schedule in metastatic breast cancer (MBC) patients.
Methods
Eligible patients had MBC and received one prior chemotherapy regimen for metastatic disease; Performance status (PS) 0–2; measurable disease (RECIST criteria). PEM(500 mg/m2) was administered intravenously (IV) over 10 min prior to GEM(1,500 mg/m2) IV given over 30 min on day 1 every 14 days.
Results
Median age of the 16 patients in the study was 54 years (range 33–77). Fourteen patients had a PS of 0/1 and were evaluable for response. There were no reported complete or partial responses, seven patients with stable disease, six patients with disease progression and one patient with unknown response. Most common toxicities were skin rash: Grade 1/2(8) and Grade 3/4(1). Grade 3/4 non-hematological toxicities were fatigue(1); anorexia(1); pneumonia(1); peripheral ischemia(1) and elevation of liver transaminases(1). Three patients experienced febrile neutropenia (FN). This study did not meet the predefined criteria to proceed with additional accrual.
Conclusions
This regimen of PEM and GEM showed no clinical activity in the dose and schedule tested.
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Abbreviations
- CT:
-
Computed tomography
- CTCAE:
-
Common terminology criteria for adverse event
- DHFR:
-
Dihydrofolate reductase
- ECOG:
-
Eastern Cooperative Oncology Group
- FEC:
-
Anthracycline based combination therapy
- FN:
-
Febrile neutropenia
- GARFT:
-
Glycinamide ribonucleotide formyl transferase
- GEM:
-
Gemcitabine
- GET:
-
Gemcitabine combination therapy
- HER-2:
-
Human epidermal growth factor receptor-2
- IHC:
-
Immuno histo chemistry
- LY231514:
-
Pemetrexed, ALIMTA, multitargeted antifolate
- MBC:
-
Metastatic breast cancer
- NSCLC:
-
Non-small cell lung cancer
- PEM:
-
Pemetrexed
- PS:
-
Performance status
- RECIST:
-
Response evaluation criteria in solid tumors
- TS:
-
Thymidylate synthase
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Acknowledgments
The authors would like to thank Lisa Vandermeer, Jessica Verreault and Jonathan Azzi for help with manuscript preparation. This study was funded by Eli Lilly Canada.
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Dent, S.F., Gertler, S., Verma, S. et al. A phase II study of biweekly pemetrexed and gemcitabine in patients with metastatic breast cancer. Cancer Chemother Pharmacol 65, 557–561 (2010). https://doi.org/10.1007/s00280-009-1064-z
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DOI: https://doi.org/10.1007/s00280-009-1064-z