Risk of febrile neutropenia in patients receiving emerging chemotherapy regimens
- 892 Downloads
Considerable evidence exists concerning the risk of febrile neutropenia (FN) associated with well-established, older chemotherapy regimens. Little is known, however, about the risks associated with many regimens that were introduced in the past decade and have become the predominant choice for certain cohorts of patients or are increasingly being used in clinical practice.
A retrospective cohort design and US healthcare claims data (2006–2011) were employed. Study subjects included adult patients receiving the following: docetaxel + cyclophosphamide (TC), 5-FU + epirubicin + cyclophosphamide (FEC), FEC followed by docetaxel (FEC → D), or docetaxel + carboplatin + trastuzumab (TCH) for non-metastatic breast cancer; TCH for metastatic breast cancer; 5-FU + leucovorin + irinotecan + oxaliplatin (FOLFIRINOX) for metastatic pancreatic cancer; and bendamustine (with rituximab [BR], without rituximab [B-Mono]) for non-Hodgkin’s lymphoma (NHL). For each patient, the first qualifying chemotherapy course and each cycle therein were identified, as were the use of supportive care—colony-stimulating factors (CSF) and antimicrobials (AMB)—and unique FN episodes.
The crude risk (incidence proportion) of FN during the chemotherapy course ranged from 8.8 (95 % CI 8.3–9.3) to 10.6 % (9.3–12.1) among the breast cancer regimens, was slightly higher for the NHL regimens (BR, 10.5 % [8.9–12.4]; B-Mono, 14.7 % [11.2–18.9]), and was markedly higher for FOLFIRINOX (24.7 % [17.9–33.1]). Most patients developing FN required inpatient care (range, 73–90 %). Use of CSF primary prophylaxis ranged from 17 (B-Mono) to 75 % (FEC → D); use of AMB primary prophylaxis ranged from 6 (FOLFIRINOX) to 13 % (B-Mono).
The risk of FN among patients receiving selected emerging chemotherapy regimens is considerable, and most cases require inpatient care. Use of CSF and AMB prophylaxis, however, varies substantially across regimens.
KeywordsFebrile neutropenia Chemotherapy Breast cancer Non-Hodgkin’s lymphoma Pancreatic cancer
Declaration of funding
Funding for this research was provided by Amgen Inc. to Policy Analysis Inc. (PAI).
Declaration of financial/other relationships
Derek Weycker, John Edelsberg, and Alex Kartashov are employed by PAI. Xiaoyan Li, Rich Barron, and Hairong Xu are employed by Amgen Inc. Gary Lyman is a principal investigator on a research grant from Amgen Inc. to Duke University.
Authorship was designated based on the guidelines promulgated by the International Committee of Medical Journal Editors (2004). All persons who meet criteria for authorship are listed as authors on the title page. The contribution of each of these individuals to this study—by task—is as follows: conception and supervision (Li and Weycker), development of design (all authors), conduct of analyses (Kartashov, Weycker), interpretation of results (all authors), preparation of manuscript (Edelsberg, Weycker), and review of manuscript (all authors). All authors have read and approved the final version of the manuscript. The study sponsor reviewed the study research plan and study manuscript; data management, processing, and analyses were conducted by PAI, and all final analytic decisions were made by study investigators.
- 1.Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, Bennett CL, Cantor SB, Crawford J, Cross SJ, Demetri G, Desch CE, Pizzo PA, Schiffer CA, Schwartzberg L, Somerfield MR, Somlo G, Wade JC, Wade JL, Winn RJ, Wozniak AJ, Wolff AC (2006) 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 24:3187–3205PubMedCrossRefGoogle Scholar
- 15.Fraser J, Steele N, Al Zaman A, Yule A (2011) Are patients in clinical trials representative of the general population? Dose intensity and toxicities associated with FE100C-D chemotherapy in a non-trial population of node positive breast cancer patients compared with PACS-01 trial group. Eur J Cancer 47:215–220PubMedCrossRefGoogle Scholar
- 19.US Department of Health and Human Services (2009) Code of Federal Regulations: Title 45, public welfare; Part 46, protection of human subjects. http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html. Accessed 4 Jul 2013
- 22.Vandenberg T, Verma S, Loibl S et al (2010) Underreporting of myelotoxicity with emerging breast cancer regimens, Cancer Res 70(24 Supplement):P3-15-02Google Scholar
- 23.Roché H, Fumoleau P, Spielmann M, Canon JL, Delozier T, Serin D, Symann M, Kerbrat P, Soulié P, Eichler F, Viens P, Monnier A, Vindevoghel A, Campone M, Goudier MJ, Bonneterre J, Ferrero JM, Martin AL, Genève J, Asselain B (2006) Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. J Clin Oncol 24:5664–5671PubMedCrossRefGoogle Scholar
- 24.Jones SE, Savin MA, Holmes FA, O’Shaughnessy JA, Blum JL, Vukelja S, McIntyre KJ, Pippen JE, Bordelon JH, Kirby R, Sandbach J, Hyman WJ, Khandelwal P, Negron AG, Richards DA, Anthony SP, Mennel RG, Boehm KA, Meyer WG, Asmar L (2006) Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 24:5381–5387PubMedCrossRefGoogle Scholar
- 25.Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J, Breast Cancer International Research Group (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365:1273–1283PubMedCentralPubMedCrossRefGoogle Scholar
- 26.Valero V, Forbes J, Pegram MD, Pienkowski T, Eiermann W, von Minckwitz G, Roche H, Martin M, Crown J, Mackey JR, Fumoleau P, Rolski J, Mrsic-Krmpotic Z, Jagiello-Gruszfeld A, Riva A, Buyse M, Taupin H, Sauter G, Press MF, Slamon DJ (2011) Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens. J Clin Oncol 29:149–156PubMedCrossRefGoogle Scholar
- 27.Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardière C, Bennouna J, Bachet JB, Khemissa-Akouz F, Péré-Vergé D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M, Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364:1817–1825PubMedCrossRefGoogle Scholar
- 30.Naeim A, Henk HJ, Becker L, Chia V, Badre S, Li X, Deeter R (2013) Pegfilgrastim prophylaxis is associated with a lower risk of hospitalization of cancer patients than filgrastim prophylaxis: a retrospective United States claims analysis of granulocyte colony-stimulating factors (G-CSF). BMC Cancer 13:11PubMedCentralPubMedCrossRefGoogle Scholar
- 32.Weycker D, Malin J, Kim J, Barron R, Edelsberg J, Kartashov A, Oster G (2009) Risk of hospitalization for neutropenic complications of chemotherapy in patients with primary solid tumors receiving pegfilgrastim or filgrastim prophylaxis: a retrospective cohort study. Clin Ther 31:1069–1081PubMedCrossRefGoogle Scholar
- 33.Heaney ML, Toy EL, Vekeman F, Laliberté F, Dority BL, Perlman D, Barghout V, Duh MS (2009) Comparison of hospitalization risk and associated costs among patients receiving sargramostim, filgrastim, and pegfilgrastim for chemotherapy-induced neutropenia. Cancer 115:4839–4848PubMedCrossRefGoogle Scholar
- 36.National Comprehensive Cancer Network (NCCN) (2004) NCCN makes changes to its guidelines for treating fever and neutropenia. J Support Oncol 2:319, 355Google Scholar