Abstract
Background
Pemetrexed and carboplatin have demonstrated activity in breast cancer. Their potential synergism in experimental models and the proven efficacy of pemetrexed/platinum in other indications make pemetrexed/carboplatin an attractive combination in breast cancer. Thus, this two-stage, sequential, open-label, multicenter, phase II study assessed the efficacy and safety of pemetrexed plus carboplatin as first-line therapy in patients with locally advanced breast cancer (LABC) or metastatic breast cancer (MBC).
Patients and methods
Patients ≥ 18 years with a histologic/cytologic diagnosis and no prior chemotherapy for LABC or MBC received pemetrexed 600 mg/m2 and carboplatin AUC 5.0 on day 1 every 21 days with folic acid and vitamin B12 supplementation.
Results
From June 2003 to April 2005, 50 patients with stage IIIB (30.0%) and stage IV (70.0%) disease were enrolled at 3 study centers. Twenty-eight percent of patients previously received adjuvant chemotherapy, 46.0% had visceral metastases, and 36.0% had ≥3 organs involved. Partial responses (RECIST criteria) were achieved in 27 (54.0%) patients (ORR = 54.0%; 95% CI, 39.3–68.2%). The median response duration was 11.1 months (95% CI, 6.5–14.0 months) and the median time to disease progression was 10.3 months (95% CI, 8.3–14.6 months). CTC hematologic toxicities were grade 3/4 neutropenia (58.0%/28.0%) and grade 3 thrombocytopenia (10.0%) and anemia (18.0%). Two (4.0%) patients had febrile neutropenia, 1 of whom died. No grade 4 non-hematologic toxicities occurred. Grade 3 non-hematologic toxicities were ALT (4.0%) and AST elevation, and edema, fatigue, pruritus, rash/desquamation, and renal toxicity (2.0% each).
Conclusions
Results of this study suggest that the combination of pemetrexed and carboplatin has promising efficacy and an acceptable safety profile. Further assessment of this combination in a randomized trial of various breast cancer patient populations is warranted.
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Acknowledgements
This study was funded by Eli Lilly and Company, Indianapolis, Indiana, USA. The interim analysis was published in the American Society Clinical Oncology 2005 Annual Meeting Proceedings: Garin A, Manikhas A, Biakhov M et al (2005) A phase II study of pemetrexed plus carboplatin as first-line therapy of patients with locally advanced (LA) or metastatic breast cancer (MBC): preliminary results. J Clin Oncol 23(16S):694 (abstr).
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Garin, A., Manikhas, A., Biakhov, M. et al. A phase II study of pemetrexed and carboplatin in patients with locally advanced or metastatic breast cancer. Breast Cancer Res Treat 110, 309–315 (2008). https://doi.org/10.1007/s10549-007-9722-5
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DOI: https://doi.org/10.1007/s10549-007-9722-5