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Capecitabine and oxaliplatin in combination as first- or second-line therapy for metastatic breast cancer: a Wisconsin Oncology Network trial

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Abstract

Purpose

Several cytotoxic chemotherapy regimens are active against metastatic breast cancer; however, benefits are modest and overall prognosis remains limited. For anthracycline and taxane-pretreated metastatic breast cancer, there remains a relative paucity of therapies with significant activity. This Phase II study evaluated the combination of capecitabine and oxaliplatin (XELOX) among patients with metastatic breast cancer being treated in the first- or second-line setting.

Methods

Patients received oxaliplatin 85 mg/m2 on days 1 and 15, and capecitabine 1,500 mg/m2 twice daily on days 1–7 and 15–21 of a 28-day cycle. Patients were treated until progression or intolerable toxicity. The primary objective was to estimate the objective response rate by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria with tumor assessments every 8 weeks.

Results

Ten patients were treated of which 3 had received prior neurotoxic therapy in the metastatic setting. There were no confirmed complete responses, 5 patients had partial response, 4 patients had stable disease for at least 24 weeks, and one patient was unevaluable. Median time to progression (TTP) was 10.4 months (95 % lower confidence bound [LCB]: 5.75 months), median progression-free survival (PFS) was 14.2 months (95 % LCB: 6.14 months), and median overall survival (OS) was 19 months (95 % LCB: 12.8 months). Multiple patients experienced pain syndromes and unusual neuropathies. Other common toxicities included fatigue, diarrhea, and nausea.

Conclusions

XELOX is a promising regimen for anthracycline-pretreated metastatic breast cancer although careful patient selection is indicated and alternate dosing schedules should be explored to minimize neurologic morbidity.

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References

  1. DeSantis C, Siegel R, Bandi P, Jemal A (2011) Breast cancer statistics. CA Cancer J Clin 61(6):409–418. doi:10.3322/caac.20134

    Article  PubMed  Google Scholar 

  2. Pectasides D, Pectasides M, Farmakis D, Bountouroglou N, Nikolaou M, Koumpou M, Mylonakis N, Kosmas C (2003) Oxaliplatin plus high-dose leucovorin and 5-fluorouracil in pretreated advanced breast cancer: a phase II study. Ann Oncol 14(4):537–542

    Article  PubMed  CAS  Google Scholar 

  3. Oshaughnessy JA, Blum J, Moiseyenko V, Jones SE, Miles D, Bell D, Rosso R, Mauriac L, Osterwalder B, Burger HU, Laws S (2001) Randomized, open-label, phase II trial of oral capecitabine (Xeloda) vs. a reference arm of intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) as first-line therapy for advanced/metastatic breast cancer. Ann Oncol 12(9):1247–1254

    Article  PubMed  CAS  Google Scholar 

  4. Bajetta E, Procopio G, Celio L, Gattinoni L, Della Torre S, Mariani L, Catena L, Ricotta R, Longarini R, Zilembo N, Buzzoni R (2005) Safety and efficacy of two different doses of capecitabine in the treatment of advanced breast cancer in older women. J Clin Oncol 23(10):2155–2161. doi:10.1200/JCO.2005.02.167

    Article  PubMed  CAS  Google Scholar 

  5. Jung SH, Lee T, Kim K, George SL (2004) Admissible two-stage designs for phase II cancer clinical trials. Stat Med 23(4):561–569. doi:10.1002/sim.1600

    Article  PubMed  Google Scholar 

  6. Zamora P AdMM, Calvo L, Jara C, Virizuela JA, Yubero A, Chacon JI, Mira J, Gonzalez Baron M (2005) Capecitabine (X) as single agent in elderly patients (p) with metastatic breast cancer (MBC). J Clin Oncol, vol 23 (June 1 supplement) (843)

  7. Piccart MJ, Raymond E, Aapro M, Eisenhauer EA, Cvitkovic E (1995) Cytotoxic agents with activity in breast cancer patients previously exposed to anthracyclines: current status and future prospects. Eur J Cancer 31A(Suppl 7):S1–10

    Article  PubMed  CAS  Google Scholar 

  8. Zelek L, Cottu P, Tubiana-Hulin M, Vannetzel JM, Chollet P, Misset JL, Chouaki N, Marty M, Gamelin E, Culine S, Dieras V, Mackenzie S, Spielmann M (2002) Phase II study of oxaliplatin and fluorouracil in taxane- and anthracycline-pretreated breast cancer patients. J Clin Oncol 20(10):2551–2558

    Article  PubMed  CAS  Google Scholar 

  9. Rixe O, Ortuzar W, Alvarez M, Parker R, Reed E, Paull K, Fojo T (1996) Oxaliplatin, tetraplatin, cisplatin, and carboplatin: spectrum of activity in drug-resistant cell lines and in the cell lines of the national cancer institute’s anticancer drug screen panel. Biochem Pharmacol 52(12):1855–1865

    Article  PubMed  CAS  Google Scholar 

  10. Caussanel JP, Levi F, Brienza S, Misset JL, Itzhaki M, Adam R, Milano G, Hecquet B, Mathe G (1990) Phase I trial of 5-day continuous venous infusion of oxaliplatin at circadian rhythm-modulated rate compared with constant rate. J Natl Cancer Inst 82(12):1046–1050

    Article  PubMed  CAS  Google Scholar 

  11. Delpeuch A, Leveque D, Rob L, Bergerat JP (2011) Off-label use of oxaliplatin in patients with metastatic breast cancer. Anticancer Res 31(5):1765–1767

    PubMed  CAS  Google Scholar 

  12. Blum JL, Jones SE, Buzdar AU, LoRusso PM, Kuter I, Vogel C, Osterwalder B, Burger HU, Brown CS, Griffin T (1999) Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer. J Clin Oncol 17(2):485–493

    PubMed  CAS  Google Scholar 

  13. Talbot DC, Moiseyenko V, Van Belle S, O’Reilly SM, Alba Conejo E, Ackland S, Eisenberg P, Melnychuk D, Pienkowski T, Burger HU, Laws S, Osterwalder B (2002) Randomised, phase II trial comparing oral capecitabine (Xeloda) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines. Br J Cancer 86(9):1367–1372. doi:10.1038/sj.bjc.6600261

    Article  PubMed  CAS  Google Scholar 

  14. Polyzos A, Gogas H, Markopoulos C, Tsavaris N, Papadopoulos O, Polyzos K, Giannopoulos A (2009) Salvage chemotherapy with oxaliplatin and capecitabine for breast cancer patients pretreated with anthracyclines and taxanes. Anticancer Res 29(7):2851–2856

    PubMed  CAS  Google Scholar 

  15. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European organization for research and treatment of cancer, national cancer institute of the United States, national cancer institute of Canada. J Natl Cancer Inst 92(3):205–216

    Article  PubMed  CAS  Google Scholar 

  16. Scheithauer W, Kornek GV, Raderer M, Schull B, Schmid K, Kovats E, Schneeweiss B, Lang F, Lenauer A, Depisch D (2003) Randomized multicenter phase II trial of two different schedules of capecitabine plus oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 21(7):1307–1312

    Article  PubMed  CAS  Google Scholar 

  17. Institute NC (2006) Common toxicity criteria for adverse events v 3.0 (CTCAE). http://ctep.cancer.gov. Accessed 10 Feb 2012

  18. Sparano JA, Vrdoljak E, Rixe O, Xu B, Manikhas A, Medina C, Da Costa SC, Ro J, Rubio G, Rondinon M, Perez Manga G, Peck R, Poulart V, Conte P (2010) Randomized phase III trial of ixabepilone plus capecitabine versus capecitabine in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 28(20):3256–3263. doi:10.1200/JCO.2009.24.4244

    Article  PubMed  CAS  Google Scholar 

  19. Cassidy J, Tabernero J, Twelves C, Brunet R, Butts C, Conroy T, Debraud F, Figer A, Grossmann J, Sawada N, Schoffski P, Sobrero A, Van Cutsem E, Diaz-Rubio E (2004) XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer. J Clin Oncol 22(11):2084–2091. doi:10.1200/JCO.2004.11.069

    Article  PubMed  CAS  Google Scholar 

  20. Comella P, Massidda B, Palmeri S, Farris A, Lucia LD, Natale D, Maiorino L, Tafuto S, Cataldis GD, Casaretti R (2005) Biweekly oxaliplatin combined with oral capecitabine (OXXEL regimen) as first-line treatment of metastatic colorectal cancer patients: a Southern Italy cooperative oncology group phase II study. Cancer Chemother Pharmacol 56(5):481–486. doi:10.1007/s00280-005-1003-6

    Article  PubMed  CAS  Google Scholar 

  21. Xiang XJ, Zhang L, Qiu F, Yu F, Zhan ZY, Feng M, Yan J, Zhao JG, Xiong JP (2012) A phase II study of capecitabine plus oxaliplatin as first-line chemotherapy in elderly patients with advanced gastric cancer. Chemotherapy 58(1):1–7. doi:10.1159/000335585

    Article  PubMed  CAS  Google Scholar 

  22. Ruzzo A, Graziano F, Loupakis F, Rulli E, Canestrari E, Santini D, Catalano V, Ficarelli R, Maltese P, Bisonni R, Masi G, Schiavon G, Giordani P, Giustini L, Falcone A, Tonini G, Silva R, Mattioli R, Floriani I, Magnani M (2007) Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFOX-4 chemotherapy. J Clin Oncol 25(10):1247–1254. doi:10.1200/JCO.2006.08.1844

    Article  PubMed  CAS  Google Scholar 

  23. Lecomte T, Landi B, Beaune P, Laurent-Puig P, Loriot MA (2006) Glutathione S-transferase P1 polymorphism (Ile105Val) predicts cumulative neuropathy in patients receiving oxaliplatin-based chemotherapy. Clin Cancer Res 12(10):3050–3056. doi:10.1158/1078-0432.CCR-05-2076

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was funded by the National Institutes of Health (NIH) grant P30 CA014520 to the University of Wisconsin Carbone Cancer Center (K.K.). We are grateful to all patients who participated in the study and staff members of the WON and the University of Wisconsin Carbone Cancer Center (UWCCC) for their help and assistance.

Conflict of interest

None.

Ethical Standards

All human studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. All persons gave their informed consent prior to inclusion in the study.

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Authors and Affiliations

  1. Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    U. O. Njiaju, A. J. Tevaarwerk, J. E. Chang, T. L. Champeny, A. M. Traynor, S. Meadows, L. Van Ummersen & J. A. Stewart

  2. Carbone Cancer Center, University of Wisconsin, 1111 Highland Ave, WIMR 6053, Madison, WI, 53719, USA

    U. O. Njiaju, A. J. Tevaarwerk, K. Kim, J. E. Chang, T. L. Champeny, A. M. Traynor, S. Meadows, L. Van Ummersen, K. Powers & J. A. Stewart

  3. Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    K. Kim

  4. Regional Cancer Center at ProHealth Care, Oconomowoc Memorial Hospital, Oconomowoc, WI, USA

    R. M. Hansen

  5. Wisconsin Oncology Network (WON), Madison, WI, USA

    A. M. Traynor & K. Powers

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  1. U. O. Njiaju
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  2. A. J. Tevaarwerk
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  3. K. Kim
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  8. S. Meadows
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  9. L. Van Ummersen
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Correspondence to U. O. Njiaju.

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Njiaju, U.O., Tevaarwerk, A.J., Kim, K. et al. Capecitabine and oxaliplatin in combination as first- or second-line therapy for metastatic breast cancer: a Wisconsin Oncology Network trial. Cancer Chemother Pharmacol 71, 613–618 (2013). https://doi.org/10.1007/s00280-012-2044-2

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  • DOI: https://doi.org/10.1007/s00280-012-2044-2

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