The prophylactic effects of long-acting granulocyte colony-stimulating factor for febrile neutropenia in newly diagnosed patients with epithelial ovarian cancer: a randomised controlled study

Lei Li, Shuiqing Ma, Ming Wu, Xianjie Tan, Sen Zhong, Jinghe Lang, Lei Li, Shuiqing Ma, Ming Wu, Xianjie Tan, Sen Zhong, Jinghe Lang

Abstract

Objective: This study explored the prophylactic effects of long-acting granulocyte colony-stimulating factor (G-CSF) for febrile neutropenia (FN) in newly diagnosed patients with epithelial ovarian cancer (EOC).

Methods: Patients were randomised into a study group (long-acting G-CSF for all chemotherapy cycles) and a control group (short-acting G-CSF for first cycle and treatment per physician discretion for subsequent cycles) at a ratio of 1:2. The incidences of FN and myelosuppression and the number of clinical visits, medication doses, complete blood count (CBC) tests and adverse events were compared between the two groups. A regression model was used to determine the risk factors for FN.

Results: From 30 November 2018 to 1 April 2019, 84 cases were included in the final analysis; there were 24 (28.6%) and 60 (71.4%) patients in the study and control groups, respectively, and 605 chemotherapy cycles. The study group or chemotherapy cycles utilising long-acting G-CSF had significantly fewer utilisations and doses of short-acting G-CSF; clinical visits; CBC tests; and incidences of FN and myelosuppression; and less G-CSF-associated pain. The utilisation of G-CSF was the only independent factor for FN in a binary regression model.

Conclusion: Long-acting G-CSF could effectively reduce the incidences of FN and myelosuppression and had mild adverse effects in newly diagnosed patients with EOC receiving chemotherapy.

Trial registration number: NCT03740464.

Keywords: Granulocyte colony-stimulating factor; adverse events; febrile neutropenia; myelosuppression; ovarian cancer.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Flow diagram of the study. G-CSF, granulocyte colony-stimulating factor.

References

    1. Geissler K, Gunzer M, Ostermann H. How safe is the administration of long-acting granulocyte colony-stimulating factor in cancer patients? Oncol Res Treat 2018;41:316–26. 10.1159/000486681
    1. Yang B-B, Savin MA, Green M. Prevention of chemotherapy-induced neutropenia with pegfilgrastim: pharmacokinetics and patient outcomes. Chemotherapy 2012;58:387–98. 10.1159/000345626
    1. Vogel CL, Wojtukiewicz MZ, Carroll RR, et al. . First and subsequent cycle use of pegfilgrastim prevents febrile neutropenia in patients with breast cancer: a multicenter, double-blind, placebo-controlled phase III study. J Clin Oncol 2005;23:1178–84. 10.1200/JCO.2005.09.102
    1. Vose JM, Crump M, Lazarus H, et al. . Randomized, multicenter, open-label study of pegfilgrastim compared with daily filgrastim after chemotherapy for lymphoma. J Clin Oncol 2003;21:514–9. 10.1200/JCO.2003.03.040
    1. Green MD, Koelbl H, Baselga J, et al. . A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Ann Oncol 2003;14:29–35. 10.1093/annonc/mdg019
    1. Holmes FA, O'Shaughnessy JA, Vukelja S, et al. . Blinded, randomized, multicenter study to evaluate single administration pegfilgrastim once per cycle versus daily filgrastim as an adjunct to chemotherapy in patients with high-risk stage II or stage III/IV breast cancer. J Clin Oncol 2002;20:727–31. 10.1200/JCO.2002.20.3.727
    1. Wang L, Baser O, Kutikova L, et al. . The impact of primary prophylaxis with granulocyte colony-stimulating factors on febrile neutropenia during chemotherapy: a systematic review and meta-analysis of randomized controlled trials. Support Care Cancer 2015;23:3131–40. 10.1007/s00520-015-2686-9
    1. Mitchell S, Li X, Woods M, et al. . Comparative effectiveness of granulocyte colony-stimulating factors to prevent febrile neutropenia and related complications in cancer patients in clinical practice: a systematic review. J Oncol Pharm Pract 2016;22:702–16. 10.1177/1078155215625459
    1. Pfeil AM, Allcott K, Pettengell R, et al. . Efficacy, effectiveness and safety of long-acting granulocyte colony-stimulating factors for prophylaxis of chemotherapy-induced neutropenia in patients with cancer: a systematic review. Support Care Cancer 2015;23:525–45. 10.1007/s00520-014-2457-z
    1. Cornes P, Gascon P, Chan S, et al. . Systematic review and meta-analysis of short- versus long-acting granulocyte colony-stimulating factors for reduction of chemotherapy-induced febrile neutropenia. Adv Ther 2018;35:1816–29. 10.1007/s12325-018-0798-6
    1. Flores IQ, Ershler W. Managing neutropenia in older patients with cancer receiving chemotherapy in a community setting. Clin J Oncol Nurs 2010;14:81–6. 10.1188/10.CJON.81-86
    1. Spunt SL, Irving H, Frost J, et al. . Phase II, randomized, open-label study of pegfilgrastim-supported VDC/IE chemotherapy in pediatric sarcoma patients. J Clin Oncol 2010;28:1329–36. 10.1200/JCO.2009.24.8872
    1. Klastersky J, de Naurois J, Rolston K, et al. . Management of febrile neutropaenia: ESMO clinical practice guidelines. Ann Oncol 2016;27(suppl 5):v111–8. 10.1093/annonc/mdw325
    1. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Myeloid growth factor. version 1., 2018. Available:
    1. Smith TJ, Bohlke K, Lyman GH, et al. . Recommendations for the use of WBC growth factors: American Society of clinical oncology clinical practice guideline update. J Clin Oncol 2015;33:3199–212. 10.1200/JCO.2015.62.3488
    1. Aapro MS, Bohlius J, Cameron DA, et al. . 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 tumours. Eur J Cancer 2011;47:8–32. 10.1016/j.ejca.2010.10.013
    1. Schuman SI, Lambrou N, Robson K, et al. . Pegfilgrastim dosing on same day as myelosuppressive chemotherapy for ovarian or primary peritoneal cancer. J Support Oncol 2009;7:225–8.
    1. Balducci L, Al-Halawani H, Charu V, et al. . Elderly cancer patients receiving chemotherapy benefit from first-cycle pegfilgrastim. Oncologist 2007;12:1416–24. 10.1634/theoncologist.12-12-1416
    1. Burris HA, Belani CP, Kaufman PA, et al. . 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 2010;6:133–40. 10.1200/JOP.091094
    1. Willis F, Woll P, Theti D, et al. . Pegfilgrastim for peripheral CD34+ mobilization in patients with solid tumours. Bone Marrow Transplant 2009;43:927–34. 10.1038/bmt.2008.411
    1. Petru E, Singer CF, Polterauer S, et al. . Prophylactic long-acting granulocyte-colony stimulating factors (G-CSF) in gynecologic malignancies: an oncologic expert statement. Wien Med Wochenschr 2015;165:387–94. 10.1007/s10354-015-0392-3
    1. Chan A, Leng XZ, Chiang JYL, et al. . Comparison of daily filgrastim and pegfilgrastim to prevent febrile neutropenia in Asian lymphoma patients. Asia Pac J Clin Oncol 2011;7:75–81. 10.1111/j.1743-7563.2010.01355.x
    1. Common terminology criteria for adverse events (CTCAE) v4.03. National Cancer Institute. Available:
    1. Kunos C, Deng W, Dawson D, et al. . A phase I-II evaluation of veliparib (NSC #737664), topotecan, and filgrastim or pegfilgrastim in the treatment of persistent or recurrent carcinoma of the uterine cervix: an NRG Oncology/Gynecologic Oncology Group study. Int J Gynecol Cancer 2015;25:484–92. 10.1097/IGC.0000000000000380
    1. Tiersten AD, Sill MW, Knight D, et al. . A phase I trial of dose-dense (biweekly) carboplatin combined with paclitaxel and pegfilgrastim: a feasibility study in patients with untreated stage III and IV ovarian, tubal or primary peritoneal cancer: a gynecologic Oncology Group study. Gynecol Oncol 2010;118:303–7. 10.1016/j.ygyno.2010.05.020
    1. Pinter T, Klippel Z, Cesas A, et al. . A phase III, randomized, double-blind, placebo-controlled trial of pegfilgrastim in patients receiving first-line FOLFOX/Bevacizumab or FOLFIRI/Bevacizumab for locally advanced or metastatic colorectal cancer: final results of the pegfilgrastim and anti-VEGF evaluation study (paves). Clin Colorectal Cancer 2017;16:103–14. 10.1016/j.clcc.2016.08.008
    1. Lyman GH, Allcott K, Garcia J, et al. . The effectiveness and safety of same-day versus next-day administration of long-acting granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced neutropenia: a systematic review. Support Care Cancer 2017;25:2619–29. 10.1007/s00520-017-3703-y
    1. Aapro M, Boccia R, Leonard R, et al. . Refining the role of pegfilgrastim (a long-acting G-CSF) for prevention of chemotherapy-induced febrile neutropenia: consensus guidance recommendations. Support Care Cancer 2017;25:3295–304. 10.1007/s00520-017-3842-1
    1. Li Y, Klippel Z, Shih X, et al. . Trajectory of absolute neutrophil counts in patients treated with pegfilgrastim on the day of chemotherapy versus the day after chemotherapy. Cancer Chemother Pharmacol 2016;77:703–12. 10.1007/s00280-016-2970-5
    1. Loibl S, Mueller V, von Minckwitz G, et al. . Comparison of pegfilgrastim on day 2 vs. day 4 as primary prophylaxis of intense dose-dense chemotherapy in patients with node-positive primary breast cancer within the prospective, multi-center gain study: (GBG 33). Support Care Cancer 2011;19:1789–95. 10.1007/s00520-010-1020-9
    1. Qin Y, Han X, Wang L, et al. . A phase I study of different doses and frequencies of pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) in patients with standard-dose chemotherapy-induced neutropenia. Chin J Cancer Res 2017;29:402–10. 10.21147/j.issn.1000-9604.2017.05.04
    1. Aarts MJ, Peters FP, Mandigers CM, et al. . Primary granulocyte colony-stimulating factor prophylaxis during the first two cycles only or throughout all chemotherapy cycles in patients with breast cancer at risk for febrile neutropenia. J Clin Oncol 2013;31:4290–6. 10.1200/JCO.2012.44.6229
    1. Aarts MJ, Grutters JP, Peters FP, et al. . Cost effectiveness of primary pegfilgrastim prophylaxis in patients with breast cancer at risk of febrile neutropenia. J Clin Oncol 2013;31:4283–9. 10.1200/JCO.2012.48.3644
    1. Bondarenko IM, Bias P, Buchner A. Incidence of bone pain in patients with breast cancer treated with lipegfilgrastim or pegfilgrastim: an integrated analysis from phase II and III studies. Support Care Cancer 2016;24:267–73. 10.1007/s00520-015-2777-7
    1. Shirasawa M, Nakahara Y, Niwa H, et al. . Interstitial pneumonia following administration of pegfilgrastim during carboplatin and etoposide chemotherapy for small-cell lung cancer. Mol Clin Oncol 2016;5:714–6. 10.3892/mco.2016.1062
    1. Llamas-Velasco M, García-Martín P, Sánchez-Pérez J, et al. . Sweet's syndrome with subcutaneous involvement associated with pegfilgrastim treatment: first reported case. J Cutan Pathol 2013;40:46–9. 10.1111/cup.12042
    1. Perrier L, Lefranc A, Pérol D, et al. . Cost effectiveness of pegfilgrastim versus filgrastim after high-dose chemotherapy and autologous stem cell transplantation in patients with lymphoma and myeloma: an economic evaluation of the palm trial. Appl Health Econ Health Policy 2013;11:129–38. 10.1007/s40258-013-0011-7
    1. Miyake O, Murata K, Tanaka S, et al. . Costs associated with febrile neutropenia in Japanese patients with primary breast cancer: post-hoc analysis of a randomized clinical trial. Jpn J Clin Oncol 2018;48:410–6. 10.1093/jjco/hyy030
    1. Blackwell K, Gascon P, Jones CM, et al. . Pooled analysis of two randomized, double-blind trials comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer. Ann Oncol 2017;28:2272–7. 10.1093/annonc/mdx303
    1. Zhou C, Huang Y, Wang D, et al. . A randomized multicenter phase III study of single administration of Mecapegfilgrastim (HHPG-19K), a pegfilgrastim Biosimilar, for prophylaxis of chemotherapy-induced neutropenia in patients with advanced non-small-cell lung cancer (NSCLC). Clin Lung Cancer 2016;17:119–27. 10.1016/j.cllc.2015.12.002
    1. Volovat C, Bondarenko I, Gladkov O, et al. . Efficacy and safety of lipegfilgrastim compared with placebo in patients with non-small cell lung cancer receiving chemotherapy: post hoc analysis of elderly versus younger patients. Support Care Cancer 2016;24:4913–20. 10.1007/s00520-016-3347-3
    1. Bondarenko I, Gladkov OA, Elsaesser R, et al. . Efficacy and safety of lipegfilgrastim versus pegfilgrastim: a randomized, multicenter, active-control phase 3 trial in patients with breast cancer receiving doxorubicin/docetaxel chemotherapy. BMC Cancer 2013;13:386 10.1186/1471-2407-13-386

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi