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Published in: Breast Cancer Research and Treatment 1/2017

01-01-2017 | Review

Optimal primary febrile neutropenia prophylaxis for patients receiving docetaxel–cyclophosphamide chemotherapy for breast cancer: a systematic review

Authors: Ricardo Fernandes, Sasha Mazzarello, Carol Stober, Lisa Vandermeer, Shaan Dudani, Mohamed F. K. Ibrahim, Habeeb Majeed, Kirstin Perdrizet, Risa Shorr, Brian Hutton, Dean Fergusson, Mark Clemons

Published in: Breast Cancer Research and Treatment | Issue 1/2017

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Abstract

Background

Due to the high rate of febrile neutropenia (FN) with docetaxel–cyclophosphamide (DC) chemotherapy, primary FN prophylaxis is recommended. However, the optimal choice of prophylaxis [i.e., granulocyte-colony stimulating factors (G-CSF) or antibiotics] is unknown. A systematic review was performed to address this knowledge gap.

Methods

Embase, Ovid Medline, Pubmed, the Cochrane database of systematic reviews, and Cochrane register of controlled trials were searched from 1946 to April 2016 for studies evaluating primary prophylactic FN treatments in breast cancer patients receiving DC chemotherapy. Outcome measures evaluated included: incidence of FN and treatment-related hospitalizations, chemotherapy dose reduction/delays/discontinuations, and adverse events. Screening and data collection were performed by two independent reviewers.

Results

Of 2105 identified records, 7 studies (n = 2535) met the pre-specified eligibility criteria. Seven additional studies (n = 621) were identified from prior systematic reviews. There were 3 randomized controlled trials (RCTs) (n = 2256) and 11 retrospective studies (n = 900). Study sample sizes ranged from 30 to 982 patients (median 99.5), evaluating pegfilgrastim (n = 1274), filgrastim (n = 1758), and oral ciprofloxacin (n = 108). Given the heterogeneity of patients and study design, a narrative synthesis of results was performed. Median FN rates with and without primary prophylaxis were 6.6 % (IQR 3.9–10.6 %) and 31.3 % (IQR 25–33 %), respectively. No FN-related deaths were reported. No RCT directly compared G-CSF with antibiotic interventions.

Conclusions

Primary FN prophylaxis reduces the incidence of FN. Despite considerable cost and toxicity differences between G-CSF and antibiotics, there is insufficient data to make a recommendation of one strategy over another.
Appendix
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Literature
1.
go back to reference Fishe B, Jeong JH, Dignam J et al (2001) Findings from recent National Surgical Adjuvant Breast and Bowel Project (NSABP) adjuvant studies in stage I breast cancer. J Natl Cancer Inst Monogr 30:62–66CrossRef Fishe B, Jeong JH, Dignam J et al (2001) Findings from recent National Surgical Adjuvant Breast and Bowel Project (NSABP) adjuvant studies in stage I breast cancer. J Natl Cancer Inst Monogr 30:62–66CrossRef
3.
go back to reference Rastogi P, Anderson SJ, Bear HD et al (2008) Preoperative chemotherapy: updates of National surgical adjuvant breast and bowel protocols B-18 and B-27. J Clin Oncol 26(5):778–785CrossRefPubMed Rastogi P, Anderson SJ, Bear HD et al (2008) Preoperative chemotherapy: updates of National surgical adjuvant breast and bowel protocols B-18 and B-27. J Clin Oncol 26(5):778–785CrossRefPubMed
4.
go back to reference Jones S, Holmes FA, O’Shaughnessy J et al (2009) Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research Trial 9735. J Clin Oncol 27(8):1177–1183CrossRefPubMed Jones S, Holmes FA, O’Shaughnessy J et al (2009) Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research Trial 9735. J Clin Oncol 27(8):1177–1183CrossRefPubMed
5.
go back to reference Jones SE, Savin MA, Holmes FA et al (2006) Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 24(34):5381–5387CrossRefPubMed Jones SE, Savin MA, Holmes FA et al (2006) Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 24(34):5381–5387CrossRefPubMed
6.
go back to reference Culakova E, Thota R, Poniewierski MS et al (2014) Patterns of chemotherapy-associated toxicity and supportive care in US oncology practice: a nationwide prospective cohort study. Cancer Med 2:434–444CrossRef Culakova E, Thota R, Poniewierski MS et al (2014) Patterns of chemotherapy-associated toxicity and supportive care in US oncology practice: a nationwide prospective cohort study. Cancer Med 2:434–444CrossRef
7.
go back to reference Lathia N, Mittmann N, De Angelis C et al (2010) Evaluation of direct medical costs of hospitalization for febrile neutropenia. Cancer 116:742–748CrossRefPubMed Lathia N, Mittmann N, De Angelis C et al (2010) Evaluation of direct medical costs of hospitalization for febrile neutropenia. Cancer 116:742–748CrossRefPubMed
8.
go back to reference Dinan MA, Hirsch BR, Lyman GH (2015) Management of chemotherapy-induced neutropenia: measuring quality, cost, and value. J Natl Compr Cancer Netw 13:e1–e7 Dinan MA, Hirsch BR, Lyman GH (2015) Management of chemotherapy-induced neutropenia: measuring quality, cost, and value. J Natl Compr Cancer Netw 13:e1–e7
9.
go back to reference Do T, Medhekar R, Bhat R et al (2015) The risk of febrile neutropenia and need for G-CSF primary prophylaxis with the docetaxel and cyclophosphamide regimen in early-stage breast cancer patients: a meta-analysis. Breast Cancer Res Treat 153(3):591–597CrossRefPubMed Do T, Medhekar R, Bhat R et al (2015) The risk of febrile neutropenia and need for G-CSF primary prophylaxis with the docetaxel and cyclophosphamide regimen in early-stage breast cancer patients: a meta-analysis. Breast Cancer Res Treat 153(3):591–597CrossRefPubMed
10.
go back to reference Younis T, Rayson D, Thompson K (2012) Primary G-CSF prophylaxis for adjuvant TC or FEC-D chemotherapy outside of clinical trial settings: a systematic review and meta-analysis. Support Care Cancer 20(10):2523–2530CrossRefPubMed Younis T, Rayson D, Thompson K (2012) Primary G-CSF prophylaxis for adjuvant TC or FEC-D chemotherapy outside of clinical trial settings: a systematic review and meta-analysis. Support Care Cancer 20(10):2523–2530CrossRefPubMed
13.
go back to reference Aapro M, Bohlius J, Cameron D et al (2011) 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumors. Eur J Cancer 47:8–32CrossRefPubMed Aapro M, Bohlius J, Cameron D et al (2011) 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumors. Eur J Cancer 47:8–32CrossRefPubMed
14.
go back to reference Smith TJ, Bohlke K, Lyman GH et al (2015) Recommendations for the use of WBC growth factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 33(28):3199–3212CrossRefPubMed Smith TJ, Bohlke K, Lyman GH et al (2015) Recommendations for the use of WBC growth factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 33(28):3199–3212CrossRefPubMed
15.
go back to reference Skedgel C, Rayson D, Younis T (2016) Is febrile neutropenia prophylaxis with granulocyte-colony stimulating factors economically justified for adjuvant TC chemotherapy in breast cancer? Support Care Cancer 24(1):387–394CrossRefPubMed Skedgel C, Rayson D, Younis T (2016) Is febrile neutropenia prophylaxis with granulocyte-colony stimulating factors economically justified for adjuvant TC chemotherapy in breast cancer? Support Care Cancer 24(1):387–394CrossRefPubMed
16.
go back to reference Higgins JPT, Green S (ed) (2011) Cochrane handbook for systematic reviews of interventions Version 5.1.0. The Cochrane Collaboration Higgins JPT, Green S (ed) (2011) Cochrane handbook for systematic reviews of interventions Version 5.1.0. The Cochrane Collaboration
17.
go back to reference Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097CrossRefPubMedPubMedCentral Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097CrossRefPubMedPubMedCentral
18.
go back to reference Gluz O, Hofmann D, Von SR et al (2014) Febrile neutropenia (FN) and infections under adjuvant chemotherapy of breast cancer with 6 × TC vs. 4 × EC-4 × Doc: toxicity data of the WSG planB trial. Oncol Res Treat 37:14–15CrossRef Gluz O, Hofmann D, Von SR et al (2014) Febrile neutropenia (FN) and infections under adjuvant chemotherapy of breast cancer with 6 × TC vs. 4 × EC-4 × Doc: toxicity data of the WSG planB trial. Oncol Res Treat 37:14–15CrossRef
19.
go back to reference Kosaka Y, Rai Y, Masuda N et al (2015) Phase III placebo-controlled, double-blind, randomized trial of pegfilgrastim to reduce the risk of febrile neutropenia in breast cancer patients receiving docetaxel/cyclophosphamide chemotherapy. Support Care Cancer 23(4):1137–1143CrossRefPubMedPubMedCentral Kosaka Y, Rai Y, Masuda N et al (2015) Phase III placebo-controlled, double-blind, randomized trial of pegfilgrastim to reduce the risk of febrile neutropenia in breast cancer patients receiving docetaxel/cyclophosphamide chemotherapy. Support Care Cancer 23(4):1137–1143CrossRefPubMedPubMedCentral
20.
go back to reference Yu JL, Chan K, Kurin M et al (2015) Clinical outcomes and cost-effectiveness of primary prophylaxis of febrile neutropenia during adjuvant docetaxel and cyclophosphamide chemotherapy for breast cancer. Breast J 21(6):658–664CrossRefPubMed Yu JL, Chan K, Kurin M et al (2015) Clinical outcomes and cost-effectiveness of primary prophylaxis of febrile neutropenia during adjuvant docetaxel and cyclophosphamide chemotherapy for breast cancer. Breast J 21(6):658–664CrossRefPubMed
21.
go back to reference Yerushalmi R, Goldvaser H, Sulkes A et al (2014) Adjuvant docetaxel and cyclophosphamide (DC) with prophylactic granulocyte colony-stimulating factor (G-CSF) on days 8 & 12 in breast cancer patients: a retrospective analysis. PLoS ONE 9(10):e107273CrossRefPubMedPubMedCentral Yerushalmi R, Goldvaser H, Sulkes A et al (2014) Adjuvant docetaxel and cyclophosphamide (DC) with prophylactic granulocyte colony-stimulating factor (G-CSF) on days 8 & 12 in breast cancer patients: a retrospective analysis. PLoS ONE 9(10):e107273CrossRefPubMedPubMedCentral
22.
go back to reference Caley A, Bertelli G, Rolles M et al (2010) Adjuvant taxane chemotherapy is associated with a significant risk of febrile neutropenia. Eur J Cancer Suppl 8(3):70CrossRef Caley A, Bertelli G, Rolles M et al (2010) Adjuvant taxane chemotherapy is associated with a significant risk of febrile neutropenia. Eur J Cancer Suppl 8(3):70CrossRef
23.
go back to reference Yau T-K, Ng T-Y, Soong IS et al (2009) Toxicity of docetaxel plus cyclophosphamide as adjuvant therapy for breast cancer in Chinese patients - The Hong Kong experience. Asia Pac J Clin Oncol 5(2):123–128CrossRef Yau T-K, Ng T-Y, Soong IS et al (2009) Toxicity of docetaxel plus cyclophosphamide as adjuvant therapy for breast cancer in Chinese patients - The Hong Kong experience. Asia Pac J Clin Oncol 5(2):123–128CrossRef
24.
go back to reference Vogel C, Rader M, Tyulandin S et al (2005) Pegfilgrastim nearly abrogates occurrence of neutropenic events early in the course of chemotherapy: results of a phase III, randomized, double-blind, placebo-controlled study of patients with breast cancer receiving docetaxel. J Support Oncol 3(2 SUPPL. 1):58–59 Vogel C, Rader M, Tyulandin S et al (2005) Pegfilgrastim nearly abrogates occurrence of neutropenic events early in the course of chemotherapy: results of a phase III, randomized, double-blind, placebo-controlled study of patients with breast cancer receiving docetaxel. J Support Oncol 3(2 SUPPL. 1):58–59
25.
go back to reference Marinho FDS, Lopes MDS, Monteiro MMF et al (2011) Incidence of febrile neutropenia with adjuvant docetaxel and cyclophosphamide in patients with early breast cancer. J Clin Oncol 29(suppl):e11501 Marinho FDS, Lopes MDS, Monteiro MMF et al (2011) Incidence of febrile neutropenia with adjuvant docetaxel and cyclophosphamide in patients with early breast cancer. J Clin Oncol 29(suppl):e11501
26.
go back to reference Soni A, Brufsky A, Jankowitz RC et al (2011) Incidence of febrile neutropenia with docetaxel plus cyclophosphamide in a university-based breast oncology clinic. J Clin Oncol 29(suppl):9061 Soni A, Brufsky A, Jankowitz RC et al (2011) Incidence of febrile neutropenia with docetaxel plus cyclophosphamide in a university-based breast oncology clinic. J Clin Oncol 29(suppl):9061
27.
go back to reference Kotasek D (2011) Febrile neutropenia rates during docetaxel and cyclophosphamide (TC) adjuvant therapy in early breast cancer (EBC). J Clin Oncol 29(suppl):1101 Kotasek D (2011) Febrile neutropenia rates during docetaxel and cyclophosphamide (TC) adjuvant therapy in early breast cancer (EBC). J Clin Oncol 29(suppl):1101
28.
go back to reference Santos FN, Cruz MR, Cezana L et al (2010) Hematologic toxicity with adjuvant docetaxel and cyclophosphamide in early breast cancer. J Clin Oncol 28(suppl)(15):e11081 Santos FN, Cruz MR, Cezana L et al (2010) Hematologic toxicity with adjuvant docetaxel and cyclophosphamide in early breast cancer. J Clin Oncol 28(suppl)(15):e11081
29.
go back to reference Vandenberg T, Younus J, Al-Khayyat S (2010) Febrile neutropenia rates with adjuvant docetaxel and cyclophosphamide chemotherapy in early breast cancer: discrepancy between published reports and community practice—a retrospective analysis. Curr Oncol 17(2):2–3CrossRefPubMedPubMedCentral Vandenberg T, Younus J, Al-Khayyat S (2010) Febrile neutropenia rates with adjuvant docetaxel and cyclophosphamide chemotherapy in early breast cancer: discrepancy between published reports and community practice—a retrospective analysis. Curr Oncol 17(2):2–3CrossRefPubMedPubMedCentral
30.
go back to reference Ngamphaiboon N, Advani PP, O’Connor TL et al (2011) Febrile neutropenia in adjuvant docetaxel and cyclophosphamide (TC) with prophylactic pegfilgrastim in patients with breast cancer: a retrospective analysis. J Clin Oncol 29(suppl):1134 Ngamphaiboon N, Advani PP, O’Connor TL et al (2011) Febrile neutropenia in adjuvant docetaxel and cyclophosphamide (TC) with prophylactic pegfilgrastim in patients with breast cancer: a retrospective analysis. J Clin Oncol 29(suppl):1134
31.
go back to reference Chan KK, Trudeau ME, Eisen A et al (2011) The cost-effectiveness of primary prophylaxis with granulocyte colony-stimulating factor in docetaxel-containing adjuvant chemotherapy in early breast cancer: the impact of risk of febrile neutropenia and its mortality. J Clin Oncol 29(suppl)(15):6086 Chan KK, Trudeau ME, Eisen A et al (2011) The cost-effectiveness of primary prophylaxis with granulocyte colony-stimulating factor in docetaxel-containing adjuvant chemotherapy in early breast cancer: the impact of risk of febrile neutropenia and its mortality. J Clin Oncol 29(suppl)(15):6086
34.
go back to reference Hautmann MG, Hipp M, Kölbl O (2011) Clostridium difficile-associated diarrhea in radiooncology: an underestimated problem for the feasibility of the radiooncological treatment? Radiat Oncol 6:89CrossRefPubMedPubMedCentral Hautmann MG, Hipp M, Kölbl O (2011) Clostridium difficile-associated diarrhea in radiooncology: an underestimated problem for the feasibility of the radiooncological treatment? Radiat Oncol 6:89CrossRefPubMedPubMedCentral
35.
go back to reference Bishop KD, Castillo JJ (2012) Risk factors associated with Clostridium difficile infection in adult oncology patients with a history of recent hospitalization for febrile neutropenia. Leuk Lymphoma 53:1617–1619CrossRefPubMed Bishop KD, Castillo JJ (2012) Risk factors associated with Clostridium difficile infection in adult oncology patients with a history of recent hospitalization for febrile neutropenia. Leuk Lymphoma 53:1617–1619CrossRefPubMed
36.
go back to reference Masaoka T, Urabe A, Ohno R et al (1998) Evidence-based recommendations on antimicrobial use in febrile neutropenia in Japan. Int J Hematol 68(Suppl 1):S5–S6 Masaoka T, Urabe A, Ohno R et al (1998) Evidence-based recommendations on antimicrobial use in febrile neutropenia in Japan. Int J Hematol 68(Suppl 1):S5–S6
38.
go back to reference Hilton J, Mazzarello S, Fergusson D et al (2016) Novel methodology for comparing standard-of-care interventions in patients with cancer. J Oncol Pract. JOPR013474 Hilton J, Mazzarello S, Fergusson D et al (2016) Novel methodology for comparing standard-of-care interventions in patients with cancer. J Oncol Pract. JOPR013474
Metadata
Title
Optimal primary febrile neutropenia prophylaxis for patients receiving docetaxel–cyclophosphamide chemotherapy for breast cancer: a systematic review
Authors
Ricardo Fernandes
Sasha Mazzarello
Carol Stober
Lisa Vandermeer
Shaan Dudani
Mohamed F. K. Ibrahim
Habeeb Majeed
Kirstin Perdrizet
Risa Shorr
Brian Hutton
Dean Fergusson
Mark Clemons
Publication date
01-01-2017
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2017
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-016-4028-0

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