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Cancer Chemotherapy and Pharmacology

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Open Access 01-04-2016 | Original Article

Trajectory of absolute neutrophil counts in patients treated with pegfilgrastim on the day of chemotherapy versus the day after chemotherapy

Authors: Yanli Li, Zandra Klippel, Xiaolong Shih, Hong Wang, Maureen Reiner, John H. Page

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2016

Abstract

Purpose

Risk of infection increases with severity and duration of chemotherapy-induced neutropenia (CIN). Pegfilgrastim is approved for use on the day after chemotherapy to reduce incidence of infection, as manifested by febrile neutropenia (FN), in patients receiving myelosuppressive chemotherapy. In this study, we compared severity and duration of absolute neutrophil count (ANC) suppression in patients who received pegfilgrastim on the same day as chemotherapy versus the next day.

Methods

We combined individual patient data from four Amgen-sponsored clinical trials in which patients with cancer were randomized to receive pegfilgrastim either the same day as chemotherapy or the next day. Severity and duration of ANC suppression were calculated using area over the curve (AOC, the area over the ANC–time response curve and below a given clinical threshold). AOC of ANC and incidences of CIN and FN were compared by day of pegfilgrastim use.

Results

The analysis included 95 same-day patients and 97 next-day patients. Despite similar ANC at baseline, ANC at nadir was higher among next-day patients than same-day patients. Mean AOC of ANC (cutoff 0.5 × 10⁹/L) among next-day patients was lower by 0.30 (95 % confidence interval: 0.16, 0.43) 10⁹/L × day than same-day patients in cycle 1. Next-day patients had lower incidences of CIN than same-day patients, but there were no significant differences in incidences of FN.

Conclusions

Patients who received pegfilgrastim the day after chemotherapy had less severe and shorter suppression of ANC than patients who received pegfilgrastim the same day as chemotherapy.

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Amulic B, Cazalet C, Hayes GL, Metzler KD, Zychlinsky A (2012) Neutrophil function: from mechanisms to disease. Annu Rev Immunol 30:459–489. doi:10.1146/annurev-immunol-020711-074942 CrossRefPubMed

Crawford J, Dale DC, Lyman GH (2004) Chemotherapy-induced neutropenia: risks, consequences, and new directions for its management. Cancer 100(2):228–237. doi:10.1002/cncr.11882 CrossRefPubMed

Crawford J, Kreisman H, Garewal H, Jones SE, Shoemaker D, Pupa MR, Armstrong S, Tomita D, Dziem G (1997) The impact of Filgrastim schedule variation on hematopoietic recovery post-chemotherapy. Ann Oncol 8(11):1117–1124CrossRefPubMed

Bodey GP, Buckley M, Sathe YS, Freireich EJ (1966) Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med 64(2):328–340CrossRefPubMed

Rivera E, Haim Erder M, Fridman M, Frye D, Hortobagyi GN (2003) First-cycle absolute neutrophil count can be used to improve chemotherapy-dose delivery and reduce the risk of febrile neutropenia in patients receiving adjuvant therapy: a validation study. Breast Cancer Res 5(5):R114–R120. doi:10.1186/bcr618 CrossRefPubMedPubMedCentral

Silber JH, Fridman M, DiPaola RS, Erder MH, Pauly MV, Fox KR (1998) First-cycle blood counts and subsequent neutropenia, dose reduction, or delay in early-stage breast cancer therapy. J Clin Oncol 16(7):2392–2400PubMed

Kuderer NM, Dale DC, Crawford J, Cosler LE, Lyman GH (2006) Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer 106(10):2258–2266. doi:10.1002/cncr.21847 CrossRefPubMed

Shayne M, Crawford J, Dale DC, Culakova E, Lyman GH, A. N. C. Study Group (2006) Predictors of reduced dose intensity in patients with early-stage breast cancer receiving adjuvant chemotherapy. Breast Cancer Res Treat 100(3):255–262. doi:10.1007/s10549-006-9254-4 CrossRefPubMed

Weycker D, Edelsberg J, Kartashov A, Barron R, Lyman G (2012) Risk and healthcare costs of chemotherapy-induced neutropenic complications in women with metastatic breast cancer. Chemotherapy 58(1):8–18. doi:10.1159/000335604 CrossRefPubMed

10.

Bhana N (2007) Granulocyte colony-stimulating factors in the management of chemotherapy-induced neutropenia: evidence based review. Curr Opin Oncol 19(4):328–335. doi:10.1097/01.cco.0000275309.58868.11 CrossRefPubMed

11.

Lyman GH, Shayne M (2007) Granulocyte colony-stimulating factors: finding the right indication. Curr Opin Oncol 19(4):299–307. doi:10.1097/CCO.0b013e3281a3c0ba CrossRefPubMed

12.

Crawford J, Ozer H, Stoller R, Johnson D, Lyman G, Tabbara I, Kris M, Grous J, Picozzi V, Rausch G, Smith R, Gradishar W, Yahanda A, Vincent M, Stewart M, Glaspy J (1991) Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Engl J Med 325(3):164–170. doi:10.1056/NEJM199107183250305 CrossRefPubMed

13.

Neulasta^® (pegfilgrastim) prescribing information. Amgen

14.

Chabner B, Longo DL (2011) Cancer chemotherapy and biotherapy: principles and practice, 5th edn. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia

15.

Meropol NJ, Miller LL, Korn EL, Braitman LE, MacDermott ML, Schuchter LM (1992) Severe myelosuppression resulting from concurrent administration of granulocyte colony-stimulating factor and cytotoxic chemotherapy. J Natl Cancer Inst 84(15):1201–1203. doi:10.1093/jnci/84.15.1201 CrossRefPubMed

16.

Weycker D, Wu H, Hagiwara M, Li X, Barron RL (2014) Use of chemotherapy and same-day pegfilgrastim prophylaxis in US clinical practice. Blood 124(21):4825

17.

Li S, Sosa IR, Molony JT, Page JH, Barron RL, Liu J, Morrow PK, Stryker S, Acquavella JF, Collins AJ (2014) Timing of primary prophylaxis G-CSF use during chemotherapy in elderly patients with NHL. Blood 124(21):6013

18.

Weycker D, Li X, Figueredo J, Barron R, Tzivelekis S, Hagiwara M (2015) Risk of chemotherapy-induced febrile neutropenia in cancer patients receiving pegfilgrastim prophylaxis: does timing of administration matter? Support Care Cancer. doi:10.1007/s00520-015-3036-7

19.

National Cancer Institute (2009) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. National Cancer Institute. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm

20.

Mosteller RD (1987) Simplified calculation of body-surface area. N Engl J Med 317(17):1098. doi:10.1056/NEJM198710223171717 PubMed

21.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®). Myeloid Growth Factors. Version 1.2015. www.NCCN.org. Accessed 20 August 2015

22.

Millward MJ, Boyer MJ, Lehnert M, Clarke S, Rischin D, Goh BC, Wong J, McNeil E, Bishop JF (2003) Docetaxel and carboplatin is an active regimen in advanced non-small-cell lung cancer: a phase II study in Caucasian and Asian patients. Ann Oncol 14(3):449–454. doi:10.1093/annonc/mdg118 CrossRefPubMed

23.

Lidstone GJ (1945) Note on logarithmic interpolation. Trans Fac Actuar 17:216–218. doi:10.1017/S0071368600002998

24.

Petrovic JS (2014) Definite integral. In: Advanced calculus: theory and practice. CRC Press, Boca Raton, pp 135-168

25.

Trillet-Lenoir V, Green J, Manegold C, Von Pawel J, Gatzemeier U, Lebeau B, Depierre A, Johnson P, Decoster G, Tomita D et al (1993) Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy. Eur J Cancer 29A(3):319–324CrossRefPubMed

26.

Brugger W, Bacon P, Lawrinson S, Romieu G (2009) Neutrophil recovery in elderly breast cancer patients receiving adjuvant anthracycline-containing chemotherapy with pegfilgrastim support. Crit Rev Oncol Hematol 72(3):265–269. doi:10.1016/j.critrevonc.2009.05.002 CrossRefPubMed

27.

Meza L, Baselga J, Holmes F, Liang B, Breddy J, for the Pegfilgrastim Study Group (2002) Incidence of febrile neutropenia (FN) is directly related to duration of severe neutropenia (DSN) after myelosuppressive chemotherapy. J Clin Oncol 21:255b (abstr 2840)

28.

Li Y, Shih X, Klippel ZK, Reiner M, Page JH (2014) Relationship between severity and duration of chemotherapy induced neutropenia and risk of infection among patients with non-myeloid malignancies. Blood 124(21):4960

29.

Burris HA, Belani CP, Kaufman PA, Gordon AN, Schwartzberg LS, Paroly WS, Shahin S, Dreiling L, Saven A (2010) Pegfilgrastim on the same day versus next day of chemotherapy in patients with breast cancer, non-small-cell lung cancer, ovarian cancer, and non-Hodgkin’s lymphoma: results of four multicenter, double-blind, randomized phase II studies. J Oncol Pract 6(3):133–140. doi:10.1200/JOP.091094 CrossRefPubMedPubMedCentral

30.

Saven A, Schwartzberg L, Kaywin P, Bartlett N, Dean L, Shahin S, Dreiling L (2006) Randomized, double-blind, phase 2, study evaluating same-day vs next-day administration of pegfilgrastim with R-CHOP in non-Hodgkin’s lymphoma patients. J Clin Oncol 24 (18_suppl; abstr 7570)

31.

Belani CP, Ramalingam S, Al-Janadi A, Eskander E, Ghazal H, Schwartzberg L, Elliott M, Shahin S, Dreiling L (2006) A randomized double-blind phase II study to evaluate same-day vs next-day administration of pegfilgrastim with carboplatin and docetaxel in patients with NSCLC. J Clin Oncol 24 (18_suppl; abstr 7110)

32.

Hoffmann PS (2005) Administration of pegfilgrastim on the same day or next day of chemotherapy. J Clin Oncol 23 (16_suppl; abstr 8137)

33.

Whitworth JM, Matthews KS, Shipman KA, Numnum TM, Kendrick JE, Kilgore LC, Straughn JM Jr (2009) The safety and efficacy of day 1 versus day 2 administration of pegfilgrastim in patients receiving myelosuppressive chemotherapy for gynecologic malignancies. Gynecol Oncol 112(3):601–604. doi:10.1016/j.ygyno.2008.10.025 CrossRefPubMed

34.

Karol J, Rybicki L, Sweetenham J, Smith MR, Hill BT, Pohlman B, Jagadeesh D, Gazdick E, Fenner K, Maggiotto AL, Dean RM (2013) Similar incidence of febrile neutropenia with same-day versus subsequent day G-CSF administration in non-Hodgkin lymphoma patients receiving R-CHOP chemotherapy. Blood 122(21):4357

35.

Cheng C, Gallagher EM, Yeh JY, Earl MA (2014) Rates of febrile neutropenia with pegfilgrastim on same day versus next day of CHOP with or without rituximab. Anticancer Drugs 25(8):964–969. doi:10.1097/CAD.0000000000000115 CrossRefPubMed

36.

Smith TJ, Bohlke K, Lyman GH, Carson KR, Crawford J, Cross SJ, Goldberg JM, Khatcheressian JL, Leighl NB, Perkins CL, Somlo G, Wade JL, Wozniak AJ, Armitage JO (2015) Recommendations for the use of WBC growth factors: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 33(28):3199–3212. doi:10.1200/JCO.2015.62.3488 CrossRefPubMed

37.

Kaufman PA, Paroly W, Rinaldi D, Sonnier S, Shahin S, Dean L, Dansey R, Burris S (2004) Randomized, double-blind, phase 2 study evaluating same-day vs next-day administration of pegfilgrastim with docetaxel, doxorubicin, and cyclophosphamide (TAC) in women with early stage and advanced breast cancer. Breast Cancer Res Treat 88(1 suppl):S59 (abstr 1054)

Title: Trajectory of absolute neutrophil counts in patients treated with pegfilgrastim on the day of chemotherapy versus the day after chemotherapy
Authors: Yanli Li
Zandra Klippel
Xiaolong Shih
Hong Wang
Maureen Reiner
John H. Page
Publication date: 01-04-2016
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 4/2016
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-016-2970-5

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