Pegfilgrastim‑induced fatigue and leukocytosis improved following dose reduction in a young patient with breast cancer: A case report

Takuwa,Haruko; Tsuji,Wakako; Goto,Tomoyuki; Otsuji,Takashi; Yotsumoto,Fumiaki

doi:10.3892/mco.2019.1907

Pegfilgrastim‑induced fatigue and leukocytosis improved following dose reduction in a young patient with breast cancer: A case report

Authors:
- Haruko Takuwa
- Wakako Tsuji
- Tomoyuki Goto
- Takashi Otsuji
- Fumiaki Yotsumoto
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Affiliations: Department of Breast Surgery, Shiga General Hospital, Moriyama, Shiga 524‑8524, Japan, Department of Medical Oncology, Shiga General Hospital, Moriyama, Shiga 524‑8524, Japan, Department of Pharmacology, Shiga General Hospital, Moriyama, Shiga 524‑8524, Japan
Published online on: August 7, 2019 https://doi.org/10.3892/mco.2019.1907
Pages: 371-375
Copyright: © Takuwa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dose‑dense (DD) chemotherapy is a treatment option for patients with high‑risk premenopausal breast cancer. Pegfilgrastim may be administered as prophylaxis against the development of febrile neutropenia and enables the continuation of the DD schedule; however, it is associated with adverse effects, including bone and muscle pain and fatigue. We herein describe our experience with pegfilgrastim administration alongside DD chemotherapy in a patient with breast cancer. A 29‑year‑old female patient was diagnosed with locally advanced breast cancer during lactation. The patient was diagnosed with cT2N1M0, stage IIB triple‑negative breast cancer and underwent four cycles of DD chemotherapy with epirubicin plus cyclophosphamide, followed by four cycles of docetaxel (DTX) every 2 weeks preoperatively, with 3.6 mg pegfilgrastim administered subcutaneously on day 3 of each cycle. The absolute neutrophil count (ANC) was 2,700, 8,400, 11,100, 13,300 and 15,000/mm3 on day 1 of each cycle. The patient experienced fatigue after each pegfilgrastim injection and was considered to be a high responder to pegfilgrastim. Therefore, 1.8 mg pegfilgrastim on day 3 of the first DD‑DTX cycle was recommended. On day 1 of the second cycle, the ANC was 13,090/mm3. The patient experienced less fatigue after the administration of 1.8 mg pegfilgrastim, but there was a significant decline in her performance status. As there is currently no evidence of pegfilgrastim dose reduction to below 1.8 mg, pegfilgrastim was omitted on day 3. On day 14, the patient developed viral enteritis, fever (38˚C), and an ANC of 297/mm3. Therefore, the third cycle was postponed. After 1 week, the patient's ANC recovered to 2,480/mm3 and she was administered the third cycle with 3.6 mg pegfilgrastim on day 3. Between January 2015 and March 2018, a total of 55 patients with breast cancer received chemotherapy with pegfilgrastim at the Shiga General Hospital. No patients other than the one presented herein experienced leukocytosis during chemotherapy. Although this was a rare complication, a dose of 1.8 mg pegfilgrastim was effective in palliating the patient's symptoms and preventing DD chemotherapy discontinuation.

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1	Mobus V, Jackisch C, Luck HJ, du Bois A, Thomssen C, Kuhn W, Nitz U, Schneeweiss A, Huober J, Harbeck N, et al: Ten-year results of intense dose-dense chemotherapy show superior survival compared with a conventional schedule in high-risk primary breast cancer: Final results of AGO phase III iddEPC trial. Ann Oncol. 29:178–185. 2018. View Article : Google Scholar : PubMed/NCBI
2	Mobus V, von Minckwitz G, Jackisch C, Luck HJ, Schneeweiss A, Tesch H, Elling D, Harbeck N, Conrad B, Fehm T, et al: German adjuvant intergroup Node-positive Study (GAIN): A phase III trial comparing two dose-dense regimens (iddEPC versus ddEC-PwX) in high-risk early breast cancer patients. Ann Oncol. 28:1803–1810. 2017.PubMed/NCBI
3	Lambertini M, Ceppi M, Cognetti F, Cavazzini G, De Lurentiis M, De Placido S, Michelotti A, Bisagni G, Durando A, Valle E, et al: Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients: A pooled analysis of the MIG1 and GIM2 phase III studies. Eur J Cancer. 71:34–42. 2017. View Article : Google Scholar : PubMed/NCBI
4	Foukakis T, von Minckwiz G, Bengtsson NO, Brandberg Y, Wallberg B, Fornander T, Mineritsch B, Schmatloch S, Singer CF, Steger G, et al: Effect of tailored dose-dense chemotherapy vs standard 3-weekly adjuvant chemotherapy on recurrence-free survival among women with high-risk early breast cancer: A Randomized Clinical Trial. JAMA. 316:1888–1896. 2016. View Article : Google Scholar : PubMed/NCBI
5	Del Mastro L, De Placido S, Bruzi P, De Laurentiis M, Boni C, Cavazzini G, Durando A, Turletti A, Nisticò C, Valle E, et al: Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: An open-label, 2 × 2 factorial, randomised phase 3 trial. Lancet. 385:1863–1872. 2015. View Article : Google Scholar : PubMed/NCBI
6	Aapro M, Boccia R, Leonard R, Camps C, Campone M, Choquet S, Danova M, Glaspy J, Hus I, Link H, 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. 25:3295–3304. 2017. View Article : Google Scholar : PubMed/NCBI
7	Vehreschild JJ, Bohme A, Cornely OA, Kahl C, Karthaus M, Kreuzer KA, Maschmeyer G, Mousset S, Ossendorf V, Penack O, et al: Prophylaxis of infectious complications with colony-stimulating factors in adult cancer patients undergoing chemotherapy-evidence-based guidelines from the infectious diseases working party AGIHO of the German society for haematology and medical oncology (DGHO). Ann Oncol. 25:1709–1718. 2014. View Article : Google Scholar : PubMed/NCBI
8	Smith TJ, Bohlke K, Lyman GH, Carson KR, Crawford J, Cross SJ, Goldberg JM, Khatcheressian JL, Leighl NB, Perkins CL, Somlo G, et al: Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 33:3199–212. 2015. View Article : Google Scholar : PubMed/NCBI
9	Aapro MS, Bohlius J, Cameron DA, Dal Lago L, Donnelly JP, Kearney N, Lyman GH, Pettengell R, Tjan-Heijnen VC, Walewski J, Weber DC, 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. 47:8–32. 2011. View Article : Google Scholar : PubMed/NCBI
10	Crawford J, Becker PS, Armitage JO, Blayney DW, Chavez J, Curtin P, Dinner S, Fynan T, Gojo I, Griffiths EA, Hough S, et al: Myeloid Growth Factors, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 15:1520–1541. 2017. View Article : Google Scholar : PubMed/NCBI
11	Green MD, Koelbl H, Baselga J, Galid A, Guillem V, Gascon P, Siena S, Lalisang RI, Samonigg H, Clemens MR, 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 Oncols. 14:29–35. 2003. View Article : Google Scholar
12	Grigg A, Solal-Celigny P, Hoskin P, Taylor K, McMillan A, Forstpointner R, Bacon P, Renwick J and Hiddemann W; International Study Group, : Open-label, randomized study of pegfilgrastim vs. daily filgrastim as an adjunct to chemotherapy in elderly patients with non-Hodgkin's lymphoma. Leuk Lymphoma. 44:1503–1508. 2003. View Article : Google Scholar : PubMed/NCBI
13	Holmes FA, Jones SE, O'Shaughnessy J, Vukelja S, George T, Savin M, Richards D, Glaspy J, Meza L, Cohen G, et al: Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia: A multicenter dose-finding study in women with breast cancer. Ann Oncol. 13:903–909. 2002. View Article : Google Scholar : PubMed/NCBI
14	Holmes FA, O'Shaughnessy JA, Vukelja S, Jones SE, Shogan J, Savin M, Glaspy J, Moore M, Meza L, Wiznitzer I, 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. 20:727–731. 2002. View Article : Google Scholar : PubMed/NCBI
15	Vose JM, Crump M, Lazarus H, Emmanouilides C, Schenkein D, Moore J, Moore J, Frankel S, Flinn I, Lovelace W, et al: Randomized, multicenter, open-label study of pegfilgrastim compared with daily filgrastim after chemotherapy for lymphoma. J Clin Oncol. 21:514–519. 2003. View Article : Google Scholar : PubMed/NCBI
16	Zhang W, Jiang Z, Wang L, Li C and Xia J: An open-label, randomized, multicenter dose-finding study of once-per-cycle pegfilgrastim versus daily filgrastim in Chinese breast cancer patients receiving TAC chemotherapy. Med Oncol. 32:1472015. View Article : Google Scholar : PubMed/NCBI
17	Cooper KL, Madan J, Whyte S, Stevenson MD and Akehurst RL: Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: Systematic review and meta-analysis. BMC Cancer. 11:4042011. View Article : Google Scholar : PubMed/NCBI
18	Pinto L, Liu Z, Doan Q, Bernal M, Dubois R and Lyman G: Comparison of pegfilgrastim with filgrastim on febrile neutropenia, grade IV neutropenia and bone pain: A meta-analysis of randomized controlled trials. Curr Med Res Opin. 23:2283–2295. 2007. View Article : Google Scholar : PubMed/NCBI
19	Masuda N, Tokuda Y, Nakamura S, Shimazaki R, Ito Y and Tamura K: Dose response of pegfilgrastim in Japanese breast cancer patients receiving six cycles of docetaxel, doxorubicin, and cyclophosphamide therapy: A randomized controlled trial. Support Care Cancer. 23:2891–2898. 2015. View Article : Google Scholar : PubMed/NCBI
20	Kosaka Y, Rai Y, Masuda N, Takano T, Saeki T, Nakamura S, Shimazaki R, Ito Y, Tokuda Y and Tamura K: 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. 23:1137–1143. 2015. View Article : Google Scholar : PubMed/NCBI
21	Pawloski PA, Larsen M, Thoresen A and Giordana MD: Pegfilgrastim use and bone pain: A cohort study of community-based cancer patients. J Oncol Pharm Pract. 22:423–429. 2016. View Article : Google Scholar : PubMed/NCBI
22	Moukharskaya J, Abrams DM, Ashikaga T, Khan F, Schwartz J, Wilson K, Verschraegen C, Openshaw T, Valentine J, Eneman J, et al: Randomized phase II study of loratadine for the prevention of bone pain caused by pegfilgrastim. Support Care Cancer. 24:3085–3093. 2016.PubMed/NCBI
23	Union for International Cancer Control-TNM classification. 8th. https://www.uicc.org/July 17–2019
24	Untch M, Jackisch C, Schneeweiss A, Conrad B, Aktas B, Denkert C, Eidtmann H, Wiebringhaus H, Kümmel S, Hilfrich J, et al: Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): A randomised, phase 3 trial. Lancet Oncol. 17:345–356. 2016. View Article : Google Scholar : PubMed/NCBI
25	Shimada H, Ueda S, Saeki T, Shigekawa T, Takeuchi H, Hirokawa E, Sugitani I, Sugiyama M, Takahashi T, Matsuura K, et al: Neoadjuvant triweekly nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide for Stage II/III HER2-negative breast cancer: Evaluation of efficacy and safety. Jpn J Clin Oncol. 45:642–649. 2015. View Article : Google Scholar : PubMed/NCBI
26	Saito M, Aogi K, Sekine I, Yoshizawa H, Yanagita Y, Sakai H, Inoue K, Kitagawa C, Ogura T and Mitsuhashi S: Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: A double-blind, double-dummy, randomised, comparative phase III trial. Lancet Oncol. 10:115–124. 2009. View Article : Google Scholar : PubMed/NCBI
27	Tsuyuki S, Senda N, Kanng Y, Yamaguchi A, Yoshibayashi H, Kikawa Y, Katakami N, Kato H, Hashimoto T, Okuno T, et al: Evaluation of the effect of compression therapy using surgical gloves on nanoparticle albumin-bound paclitaxel-induced peripheral neuropathy: A phase II multicenter study by the Kamigata Breast Cancer Study Group. Breast Cancer Res Treat. 160:61–67. 2016. View Article : Google Scholar : PubMed/NCBI
28	Lambertini M, Del Mastro L, Bellodi A and Pronzato P: The five ‘Ws’ for bone pain due to the administration of granulocyte-colony stimulating factors (G-CSFs). Crit Rev Oncol Hematol. 89:112–128. 2014. View Article : Google Scholar : PubMed/NCBI
29	Hamilton JA: Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol. 8:533–544. 2008. View Article : Google Scholar : PubMed/NCBI
30	Stosser S, Schweizerhof M and Kuner R: Hematopoietic colony-stimulating factors: New players in tumor-nerve interactions. J Mol Med (Berl). 89:321–329. 2011. View Article : Google Scholar : PubMed/NCBI
31	Package insert, . Neulasta (pegfilgrastim). Thousand Oaks, CA, Amgen. September 15–2005, https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/pegfamg013102LB.pdf#search=%27Package+insert.+Neulasta+%28pegfilgrastim%29.+Thousand+Oaks%2C+CA%3A+Amgen%2C+September+15%2C+2005.%27July 17–2019
32	Rheingold SD and Lange BJ: Oncogenic emergencies. Principkes and Practice of Pediatric Oncology. 4th. Pizzo PA and Poplack DG: Philadelphia: Lippincott Williams & Wilkins; pp. 1177–1203. 2002
33	Schirm S, Engel C, Loibl S, Loeffler M and Scholz M: Model-based optimization of G-CSF treatment during cytotoxic chemotherapy. J Cancer Res Clin Oncol. 144:343–358. 2018. View Article : Google Scholar : PubMed/NCBI
34	Ishiguro H, Kitano T, Yoshibayash i, Toi M, Ueno T, Yasuda H, Yanagihara K, Garbo CL and Fukushima M: Prolonged neutropenia after dose-dense chemotherapy with pegfilgrastim. Ann Oncol. 19:1019–1020. 2008. View Article : Google Scholar : PubMed/NCBI