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A phase II study of pemetrexed and carboplatin in patients with locally advanced or metastatic breast cancer

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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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References

  1. Calvert H (1999) An overview of folate metabolism: features relevant to the action and toxicities of antifolate anticancer agents. Semin Oncol 26(2 Suppl 6):3–10

    PubMed  CAS  Google Scholar 

  2. Mendelsohn LG, Shih C, Chen VJ et al (1999) Enzyme inhibition, polyglutamation, and the effect of LY231514 (MTA) on purine biosynthesis. Semin Oncol 26(2 Suppl 6):42–47

    PubMed  CAS  Google Scholar 

  3. Vogelzang NJ, Rusthoven JJ, Symanowski J et al (2003) Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 21:2636–2644

    Article  PubMed  CAS  Google Scholar 

  4. Hanna N, Shepherd FA, Fossella FV et al (2004) Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 22(9):1589–1597

    Article  PubMed  CAS  Google Scholar 

  5. Gomez HL, Hanauske A-R, Santillana S et al (2002) A phase II trial of pemetrexed in previously untreated breast cancer. Breast Cancer Res Treat 76(Suppl 1):S66 (abstr)

    Google Scholar 

  6. Llombart-Cussac A, Theodoulou M, Rowland K et al (2006) Pemetrexed in patients with locally advanced or metastatic breast cancer who had received previous antracycline and taxane treatment: phase II study. Clin Breast Cancer 7:380–385

    PubMed  CAS  Google Scholar 

  7. Martin M, Spielmann M, Namer M et al (2003) Phase II study of pemetrexed in breast cancer patients pretreated with anthracyclines. Ann Oncol 14:1246–1252

    Article  PubMed  CAS  Google Scholar 

  8. Miles DW, Smith IE, Coleman RE et al (2001) A phase II study of pemetrexed disodium (LY231514) in patients with locally recurrent or metastatic breast cancer. Eur J Cancer 37:1366–1371

    Article  PubMed  CAS  Google Scholar 

  9. O’Shaughnessey J, Liepa AM, Nguyen B (2002) Symptom improvement with pemetrexed for heavily pre-treated patients with advanced breast cancer. Breast Cancer Res Treat 76(Suppl 1):530 (abstr)

    Google Scholar 

  10. Ma CX, Steen P, Rowland KM et al (2006) A phase II trial of a combination of pemetrexed and gemcitabine in patients with metastatic breast cancer: an NCCTG study. Annalas of Oncology 17(2):226–231

    Article  CAS  Google Scholar 

  11. Dittrich C, Petruzelka L, Vodvarka P et al (2006) A phase I study of pemetrexed (Alimta) and cyclophosphamide in patients with locally advanced or metastatic breast cancer. Clin Cancer Res 12(23):7071–7078

    Article  PubMed  CAS  Google Scholar 

  12. Paridaens R, Dirix L, Mellaerts N et al (2003) Phase I study of pemetrexed (Alimta) and epirubicin in patients with locally advanced or metastatic breast cancer. Proc Amer Soc Clin Oncol, 21:A290 (abstr)

    Google Scholar 

  13. Crown J, Pegram M (2003) Platinum-taxane combinations in metastatic breast cancer: an evolving role in the era of molecularly targeted therapy. Breast Cancer Res Treat 79(Suppl 1):S11–18

    Article  PubMed  CAS  Google Scholar 

  14. Martin M (2001) Platinum compounds in the treatment of advanced breast cancer. Clin Breast Cancer 2:190–208

    Article  PubMed  CAS  Google Scholar 

  15. Perez EA, Hillman DW, Stell PJ et al (2000) A phase II study of paclitaxel plus carboplatin as first-line chemotherapy for women with metastatic breast carcinoma. Cancer 88:124–131

    Article  PubMed  CAS  Google Scholar 

  16. Fountzilas G, Dimopoulos AM, Papadimitriou C et al (1998) First-line chemotherapy with paclitaxel by three-hour infusion and carboplatin in advanced breast cancer (final report): a phase II study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol 9:1031–1034

    Article  PubMed  CAS  Google Scholar 

  17. Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10:1–10

    Article  PubMed  CAS  Google Scholar 

  18. Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92:205–216

    Article  PubMed  CAS  Google Scholar 

  19. National Cancer Institute (1998) Common Toxicity Criteria (version 2.0). Cited March 23

  20. Kaplan EL, Meier P (1958) Nonparametric estimation of incomplete observations. J Am Stat Assoc 53:457–481

    Article  Google Scholar 

  21. O’Shaughnessy JA, Clark RS, Blum JL et al (2005) Phase II study of pemetrexed in patients pretreated with an anthracycline, a taxane, and capecitabine for advanced breast cancer. Clin Breast Cancer 6:143–149

    PubMed  CAS  Google Scholar 

  22. Llombart-Cussac A, Martin M, Harbeck N et al (2006) Randomized, phase II study of two doses of pemetrexed as first-line chemotherapy for locally advanced or metastatic breast cancer (MBC): clinical results and exploratory pharmacogenomic analysis. J Clin Oncol 24(18S):3077 (abstr)

    Google Scholar 

  23. Perez EA (2004) Carboplatin in combination therapy for metastatic breast cancer. Oncologist 9:518–527

    Article  PubMed  CAS  Google Scholar 

  24. Valero V, Holmes FA, Walters RS et al (1995) Phase II trial of docetaxel: a new highly effective antineoplastic agent in the management of patients with anthracycline-resistant metastatic breast cancer. J Clin Oncol 13:2886–2894

    PubMed  CAS  Google Scholar 

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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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Authors and Affiliations

  1. Russian Cancer Research Center, Moscow, Russian Federation

    August Garin & Sergey Tjulandin

  2. Oncology Dispensary, S-Petersburg, Russian Federation

    Alexey Manikhas & Mikhail Chezhin

  3. Central MPS Hosp, Moscow, Russian Federation

    Mikhail Biakhov & Tatiana Ivanchenko

  4. Eli Lilly Regional Operations, Vienna, Austria

    Kurt Krejcy

  5. Eli Lilly, Moscow, Russian Federation

    Vera Karaseva

  6. Krasnopresnenskaya Nabereznaya, 18, Moscow, 123317, Russian Federation

    Vera Karaseva

Authors
  1. August Garin
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  2. Alexey Manikhas
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  3. Mikhail Biakhov
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  4. Mikhail Chezhin
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  5. Tatiana Ivanchenko
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  6. Kurt Krejcy
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  7. Vera Karaseva
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  8. Sergey Tjulandin
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Corresponding author

Correspondence to Vera Karaseva.

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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

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