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XELOX and bevacizumab followed by single-agent bevacizumab as maintenance therapy as first-line treatment in elderly patients with advanced colorectal cancer: the boxe study

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Abstract

Purpose

The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved progression-free survival (PFS) in patients with metastatic colorectal cancer (CRC). An increased risk of arterial thromboembolic events has been observed in some trials in older patients, and the potential benefit of a maintenance therapy with bevacizumab alone has not been clearly demonstrated. This phase II study was designed to evaluate the efficacy and safety of XELOX (capecitabine plus oxaliplatin) plus bevacizumab followed by bevacizumab alone in elderly patients with advanced CRC.

Methods

Treatment consisted of bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 on day 1, plus capecitabine 1,000 mg/m2 twice daily on days 1–14, every 3 weeks up to a maximum of 8 cycles. Patients then received maintenance therapy consisting of bevacizumab alone (7.5 mg/kg) once every 3 weeks up to disease progression. The primary study end-points were safety and response rate.

Results

A total of 44 patients were recruited. In an intention-to-treat analysis, the overall response rate was 52 % [95 % confidence interval (CI) 37 to 68 %], with 86 % of patients achieving disease control. Median PFS and overall survival were 11.5 months (95 % CI 10.0–12.9 months) and 19.3 months (95 % CI 16.5–22.1 months), respectively. In all, 10 patients (23 %) had grade 3/4 adverse events (AEs), the most common being diarrhea (9 %), neutropenia (7 %), peripheral neuropathy (7 %), and stomatitis (7 %). No patients died because of treatment-related AEs. The rate of bevacizumab-related AEs (hypertension, thromboembolic events, and gastrointestinal perforation) was consistent with that reported earlier in the general CRC population.

Conclusion

The combination of XELOX and bevacizumab is effective and has a manageable tolerability profile when administered to elderly patients with advanced CRC. Maintenance therapy with single-agent bevacizumab may be considered to extend PFS in this setting of patients.

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References

  1. World Health Organization (2004) GBD 2001: deaths by age, sex and cause for the year. http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_part2.pdf. Accessed 29 Nov 2010

  2. Ries LAG, Harkins D, Krapcho M, et al. (2003) Contents of the SEER cancer statistics review, 1975–2003. National Cancer Institute, Bethesda. http://seer.cancer.gov/csr/1975_2003/. Accessed 3 Aug 2010

  3. Simmonds PD, Best LY (1999) Should chemotherapy be used as a treatment of advanced colorectal carcinoma (ACC) in patients over 70 years age? Contra. Eur J Cancer 35:1640–1649

    Article  PubMed  Google Scholar 

  4. Balducci L, Extermann M (2000) Management of cancer in the older person: a practical approach. Oncologist 5:224–237

    Article  PubMed  CAS  Google Scholar 

  5. Kohne CH, Folprecht G, Goldberg RM, Mitry E, Rougier P (2008) Chemotherapy in elderly patients with colorectal cancer. Oncologist 13:390–402

    Article  PubMed  Google Scholar 

  6. Folprecht G, Cunningham D, Ross P et al (2004) Efficacy of 5-fluorouracil-based chemotherapy in elderly patients with metastatic colorectal cancer: a pooled analysis of clinical trials. Ann Oncol 15:1330–1338

    Article  PubMed  CAS  Google Scholar 

  7. Goldberg RM, Tabah-Fisch I, Bleiberg H et al (2006) Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol 24:4085–4091

    Article  PubMed  CAS  Google Scholar 

  8. Folprecht G, Seymour MT, Saltz L et al (2008) Irinotecan/fluorouracil combination in first-line therapy of older and younger patients with metastatic colorectal cancer: combined analysis of 2,691 patients in randomized controlled trials. J Clin Oncol 26:1443–1451

    Article  PubMed  CAS  Google Scholar 

  9. Sanoff HK, Bleiberg H, Goldberg RM (2007) Managing older patients with colorectal cancer. J Clin Oncol 25:1891–1897

    Article  PubMed  Google Scholar 

  10. Rosati G, Cordio S, Bordonaro R et al (2010) Capecitabine in combination with oxaliplatin or irinotecan in elderly patients with advanced colorectal cancer: results of a randomized phase II study. Ann Oncol 21:781–786

    Article  PubMed  CAS  Google Scholar 

  11. Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342

    Article  PubMed  CAS  Google Scholar 

  12. Saltz L, Clarke S, Díaz-Rubio E et al (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26:2013–2019

    Article  PubMed  CAS  Google Scholar 

  13. Kabbinavar F, Hurwitz H, Fehrenbacher L et al (2003) Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 21:60–65

    Article  PubMed  CAS  Google Scholar 

  14. Kabbinavar F, Schulz J, McCleod M et al (2005) Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol 23:3697–3705

    Article  PubMed  CAS  Google Scholar 

  15. Van Cutsem E, Rivera F, Berry S et al (2009) Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 20:1842–1847

    Article  PubMed  Google Scholar 

  16. Cohn AL, Bekaii-Saab T, Bendell JC et al (2010) Clinical outcomes in bevacizumab (BV)-treated patients (pts) with metastatic colorectal cancer (mCRC): results from ARIES observational cohort study (OCS) and confirmation of BriTE data on BV beyond progression (BBP). J Clin Oncol 28:15s Abstr 3596

    Google Scholar 

  17. Grothey A, Sugrue MM, Purdie DM et al (2008) Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BriTE). J Clin Oncol 26:5326–5334

    Article  PubMed  CAS  Google Scholar 

  18. Hochster HS, Hart LL, Ramanathan RK et al (2008) Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE study. J Clin Oncol 26:3523–3529

    Article  PubMed  CAS  Google Scholar 

  19. Díaz-Rubio E, Gómez-España A, Massutí B et al (2012) First-line XELOX plus bevacizumab followed by XELOX plus bevacizumab or single-agent bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: the phase III MACRO TTD study. Oncologist 17:15–25

    Article  PubMed  Google Scholar 

  20. Scappaticci FA, Skillings JR, Scott N et al (2007) Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst 99:1232–1239

    Article  PubMed  Google Scholar 

  21. Kabbinavar FF, Hurwitz HI, Yi J et al (2009) Addition of bevacizumab to fluorouracil-based first-line treatment of metastatic colorectal cancer: pooled analysis of cohorts of older patients from two randomized clinical trials. J Clin Oncol 27:199–205

    Article  PubMed  CAS  Google Scholar 

  22. Cassidy J, Saltz LB, Giantonio BJ et al (2010) Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies. J Cancer Res Clin Oncol 136:737–743

    Article  PubMed  CAS  Google Scholar 

  23. Therasse P, Arbuck SG, Eisenhauer EA et al (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 92:205–216

    Article  PubMed  CAS  Google Scholar 

  24. ICH website: http://www.ich.org

  25. Aaronson NK, Ahmedzai S, Bergman B et al (1993) The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 85:365–376

    Article  PubMed  CAS  Google Scholar 

  26. Simon R (1989) Optimal two stage design for phase II clinical trials. Control Clin Trial 10:1–10

    Article  CAS  Google Scholar 

  27. Kaplan EL, Meier P (1958) Non-parametric estimation from incomplete observations. J Am Stat Assoc 53:457–458

    Article  Google Scholar 

  28. Kozloff M, Yood MU, Berlin J et al (2009) Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: the BRiTE observational cohort study. Oncologist 14:862–870

    Article  PubMed  CAS  Google Scholar 

  29. Hofheinz R, Grothe W, Tummes D et al. (2012) Bevacizumab in the first-line treatment of elderly patients with metastatic colorectal cancer: mature results from a large community-based observational study. ASCO GI, Abstr 566

  30. Tol J, Koopman M, Cats A et al (2009) Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 360:563–572

    Article  PubMed  CAS  Google Scholar 

  31. Vrdoljak E, Omrčen T, Boban M, Hrabar A (2011) Phase II study of bevacizumab in combination with capecitabine as first-line treatment in elderly patients with metastatic colorectal cancer. Anticancer Drugs 22:191–197

    Article  PubMed  CAS  Google Scholar 

  32. Feliu J, Safont MJ, Salud A et al (2010) Capecitabine and bevacizumab as first-line treatment in elderly patients with metastatic colorectal cancer. Br J Cancer 102:1468–1473

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Medical Oncology Unit, S. Carlo Hospital, Via Potito Petrone, 1, 85100, Potenza, Italy

    Gerardo Rosati & Domenico Bilancia

  2. Department of Gastrointestinal Medical Oncology, National Cancer Institute, Naples, Italy

    Antonio Avallone

  3. Department of Medical Oncology, University Hospital, Udine, Italy

    Giuseppe Aprile

  4. Medical Oncology Unit, S. Giovanni di Dio Hospital, Agrigento, Italy

    Alfredo Butera

  5. Biostatistic Unit Medi Service, Genoa, Italy

    Giorgio Reggiardo

Authors
  1. Gerardo Rosati
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  2. Antonio Avallone
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  3. Giuseppe Aprile
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  4. Alfredo Butera
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  5. Giorgio Reggiardo
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  6. Domenico Bilancia
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Correspondence to Gerardo Rosati.

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Rosati, G., Avallone, A., Aprile, G. et al. XELOX and bevacizumab followed by single-agent bevacizumab as maintenance therapy as first-line treatment in elderly patients with advanced colorectal cancer: the boxe study. Cancer Chemother Pharmacol 71, 257–264 (2013). https://doi.org/10.1007/s00280-012-2004-x

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  • DOI: https://doi.org/10.1007/s00280-012-2004-x

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