DOI QR코드

DOI QR Code

Risk of Serious Neutropenic Events in Cancer Patients Treated with Bevacizumab: A Meta-analysis

  • Zhou, Fan (Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Nanchang University) ;
  • Shao, Jiang-Hua (Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Nanchang University) ;
  • Wu, Lin-Quan (Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Nanchang University) ;
  • Yin, Xiang-Bao (Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Nanchang University) ;
  • Yu, Xin (Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Nanchang University)
  • 발행 : 2013.04.30

초록

Bevacizumab has been approved for use in combination with chemotherapy to treat many types of cancer but associated neutropenic events, including febrile neutropenia, have been reported. To estimate the incidence and relative risk of neutropenic events in cancer patients treated with bevacizumab combination therapy, we searched PubMed, EMBASE, and Web of Science literature databases, as well as abstracts presented at the American Society of Clinical Oncology conferences, to identify relevant studies published from January 1966 to December 2011. Studies that compared bevacizumab plus chemotherapy or biological therapy with chemotherapy or biological therapy alone, and that had adequate safety data profiles, were selected for analysis. Statistical analyses were conducted to calculate the summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) using fixed- or random-effects models. A total of 22 clinical trials involving 15,056 patients were included in the analysis. The summary incidences of high-grade neutropenia (HGN) and high-grade febrile neutropenia (HGFN) in patients receiving bevacizumab was 27.3% (95% CI: 26.4%-28.3%) and 3.91% (95% CI: 3.51%-4.37%), respectively. The risks of HGN (RR=1.10; 95% CI: 1.02-1.19; P=0.02) and HGFN (RR=1.31; 95% CI: 1.08-1.59; P=0.005) were significantly increased in bevacizumab-treated patients, compared to those who did not receive bevacizumab. The RR of bevacizumab-associated HGN, but not HGFN, varied significantly with tumor types (P=0.005). The increased risk of bevacizumab-associated neutropenic events was dose-dependent, as the RR was greater at a dose of 5 mg/kg/week than at 2.5 mg/kg/week. Our findings suggest that bevacizumab addition to cancer therapy significantly increases the risk of serious neutropenic events, and this risk may be dose-dependent.

키워드

참고문헌

  1. Aapro MS, Cameron DA, Pettengell R, et al (2006). EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphomas and solid tumours. Eur J Cancer, 42, 2433-53. https://doi.org/10.1016/j.ejca.2006.05.002
  2. Allegra CJ, Yothers G, O'Connell MJ, et al (2009). Initial safety report of NSABP C-08: A randomized phase III study of modified FOLFOX6 with or without bevacizumab for the adjuvant treatment of patients with stage II or III colon cancer. J Clin Oncol, 27, 3385-90. https://doi.org/10.1200/JCO.2009.21.9220
  3. Baar J, Silverman P, Lyons J, et al (2009). A vasculaturetargeting regimen of preoperative docetaxel with or without bevacizumab for locally advanced breast cancer: impact on angiogenic biomarkers. Clin Cancer Res, 15, 3583-90. https://doi.org/10.1158/1078-0432.CCR-08-2917
  4. Brufsky A, Rivera RR, Hurvitz SA, et al (2010). Progression-free survival (PFS) in patient subgroups in RIBBON-2, a phase III trial of chemotherapy (chemo) plus or minus bevacizumab (BV) for second-line treatment of HER2-negative, locally recurrent or metastatic breast cancer (MBC). J Clin Oncol 28, 1021[meeting abstract].
  5. Burger RA, Brady MF, Bookman MA, et al (2010). Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): a gynecologic oncology group study. J Clin Oncol, 28, LBA1[meeting abstract].
  6. Choueiri TK, Mayer EL, Je Y, et al (2011). Congestive heart failure risk in patients with breast cancer treated with bevacizumab. J Clin Oncol, 29, 632-8. https://doi.org/10.1200/JCO.2010.31.9129
  7. Escudier B, Pluzanska A, Koralewski P, et al (2007). Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet, 370, 2103-11. https://doi.org/10.1016/S0140-6736(07)61904-7
  8. Folkman J (2002). Role of angiogenesis in tumor growth and metastasis. Semin Oncol, 29, 15-8.
  9. Geiger-Gritsch S, Stollenwerk B, Miksad R, et al (2010). Safety of bevacizumab in patients with advanced cancer: a metaanalysis of randomized controlled trials. Oncologist, 15, 1179-91. https://doi.org/10.1634/theoncologist.2009-0155
  10. Hapani S, Chu D, Wu S (2009). Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab: a meta-analysis. Lancet Oncol, 10, 559-68. https://doi.org/10.1016/S1470-2045(09)70112-3
  11. Hapani S, Sher A, Chu D, Wu S (2010). Increased risk of serious hemorrhage with bevacizumab in cancer patients: a metaanalysis. Oncology, 79, 27-38. https://doi.org/10.1159/000314980
  12. Hattori K, Heissig B, Wu Y, et al (2002). Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat Med, 8, 841-9.
  13. Herbst RS, O'Neill VJ, Fehrenbacher L, et al (2007). Phase II study of efficacy and safety of bevacizumab in combination with chemotherapy or erlotinib compared with chemotherapy alone for treatment of recurrent or refractory non small-cell lung cancer. J Clin Oncol, 25, 4743-50. https://doi.org/10.1200/JCO.2007.12.3026
  14. Hurwitz HI, Fehrenbacher L, Hainsworth JD, et al (2005). Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer. J Clin Oncol, 23, 3502-8. https://doi.org/10.1200/JCO.2005.10.017
  15. Kang Y, Ohtsu A, Van Cutsem E, et al (2010). AVAGAST: A andomized, double-blind, placebo-controlled, phase III study of first-line capecitabine and cisplatin plus bevacizumab or lacebo in patients with advanced gastric cancer (AGC). J Clin Oncol, 28, LBA4007 [meeting abstract].
  16. Karrison T, Kindler HL, Gandara DR, al e (2007). Final analysis of a multi-center, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin (GC) plus bevacizumab (B) or placebo (P) in patients (pts) with malignant mesothelioma (MM). J Clin Oncol, 25, 7526 [meeting abstract].
  17. Kelly WK, Halabi S, Carducci MA, et al (2010). A randomized, double-blind, placebo-controlled phase III trial comparing docetaxel, prednisone, and placebo with docetaxel, prednisone, and bevacizumab in men with metastatic castration-resistant prostate cancer (mCRPC): survival results of CALGB 90401. J Clin Oncol, 28, LBA4511 [meeting abstract].
  18. Kerbel RS (2008). Tumor angiogenesis. N Engl J Med, 358, 2039-49. https://doi.org/10.1056/NEJMra0706596
  19. Kindler HL, Niedzwiecki D, Hollis D, et al (2010). Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J Clin Oncol, 28, 3617-22. https://doi.org/10.1200/JCO.2010.28.1386
  20. Meade MO, Richardson WS (1997). Selecting and appraising studies for a systematic review. Ann Intern Med, 127, 531-7. https://doi.org/10.7326/0003-4819-127-7-199710010-00005
  21. Miles DW, Chan A, Dirix LY, et al (2010). Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol, 28, 3239-47. https://doi.org/10.1200/JCO.2008.21.6457
  22. Miller K, Wang M, Gralow J, et al (2007). Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med, 357, 2666-76. https://doi.org/10.1056/NEJMoa072113
  23. Moehler M, Sprinzl MF, Abdelfattah M, et al (2009). Capecitabine and irinotecan with and without bevacizumab for advanced colorectal cancer patients. World J Gastroenterol, 15, 449-56. https://doi.org/10.3748/wjg.15.449
  24. Novitskiy SV, Csiki I, Huang Y, et al (2010). Anti-vascular endothelial growth factor treatment in combination with chemotherapy delays hematopoietic recovery due to decreased proliferation of bone marrow hematopoietic progenitor cells. J Thorac Oncol, 5, 1410-5. https://doi.org/10.1097/JTO.0b013e3181e59c24
  25. Okines AF, Langley R, Cafferty FH, et al (2010). Preliminary safety data from a randomized trial of perioperative epirubicin, cisplatin plus capecitabine (ECX) with or without bevacizumab (B) in patients (pts) with gastric or oesophagogastric junction (OGJ) adenocarcinoma. J Clin Oncol, 28, 4019 [meeting abstract]. https://doi.org/10.1200/JCO.2010.31.5143
  26. Rafii S, Avecilla S, Shmelkov S, et al (2003). Angiogenic factors reconstitute hematopoiesis by recruiting stem cells from bone marrow microenvironment. Ann N Y Acad Sci, 996, 49-60. https://doi.org/10.1111/j.1749-6632.2003.tb03232.x
  27. Ranpura V, Hapani S, Wu S (2011). Treatment-related mortality with bevacizumab in cancer patients: a meta-analysis. JAMA, 305, 487-94. https://doi.org/10.1001/jama.2011.51
  28. Ranpura V, Pulipati B, Chu D, et al (2010). Increased risk of highgrade hypertension with bevacizumab in cancer patients: a meta-analysis. Am J Hypertens, 23, 460-8. https://doi.org/10.1038/ajh.2010.25
  29. Reck M, von Pawel J, Zatloukal P, et al (2009). Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous nonsmall-cell lung cancer: AVAil. J Clin Oncol, 27, 1227-34. https://doi.org/10.1200/JCO.2007.14.5466
  30. Rini BI, Halabi S, Rosenberg JE, et al (2008). Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol, 26, 5422-8. https://doi.org/10.1200/JCO.2008.16.9847
  31. Rini BI, Halabi S, Rosenberg JE, et al (2010). Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. J Clin Oncol, 28, 2137-43. https://doi.org/10.1200/JCO.2009.26.5561
  32. Robert NJ, Dieras V, Glaspy J, et al (2009). RIBBON-1: Randomized,double-blind, placebo-controlled, phase III trial of hemotherapy with or without bevacizumab (B) for first-line reatment of HER2-negative locally recurrent or metastatic reast cancer (MBC). J Clin Oncol, 27, 1005 [meeting abstract]. https://doi.org/10.1200/JCO.2008.20.4057
  33. Sakurai T, Kudo M (2011). Signaling pathways governing tumor angiogenesis. Oncology, 81, 24-9. https://doi.org/10.1159/000333256
  34. Sandler A, Gray R, Perry MC, et al (2006). Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med, 355, 2542-50. https://doi.org/10.1056/NEJMoa061884
  35. Schutz FA, Jardim DL, Je Y, Choueiri TK (2011). Haematologic toxicities associated with the addition of bevacizumab in cancer patients. Eur J Cancer, 47, 1161-74. https://doi.org/10.1016/j.ejca.2011.03.005
  36. Schutz FA, Je Y, Choueiri TK (2011). Hematologic toxicities in cancer patients treated with the multi-tyrosine kinase sorafenib: a meta-analysis of clinical trials. Crit Rev Oncol Hematol, 80, 291-300. https://doi.org/10.1016/j.critrevonc.2010.11.007
  37. Tebbutt NC, Wilson K, Gebski VJ, et al (2010). Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study. J Clin Oncol, 28, 3191-8. https://doi.org/10.1200/JCO.2009.27.7723
  38. Van Cutsem E, Vervenne WL, Bennouna J, et al (2009). Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. J Clin Oncol, 27, 2231-7. https://doi.org/10.1200/JCO.2008.20.0238
  39. Zalcman G, Margery J, Scherpereel A, et al (2010). IFCTGFPC-0701 MAPS trial, a multicenter randomized phase II/ III trial of pemetrexed-cisplatin with or without bevacizumab in patients with malignant pleural mesothelioma. J Clin Oncol, 28, 7020 [meeting abstract].

피인용 문헌

  1. Risk of hematological toxicities in patients with solid tumors treated with ramucirumab: a meta-analysis vol.11, pp.21, 2015, https://doi.org/10.2217/fon.15.178