Bone and soft tissue sarcomas, tumors of the skinBone and soft tissue sarcomas, tumors of the skinСаркомы костей, мягких тканей и опухоли кожи2219-46142782-3687Publishing House ABV Press173Concomitant and auxiliary therapyСОПУТСТВУЮЩАЯ И ВСПОМОГАТЕЛЬНАЯ ТЕРАПИЯPegfilgrastim in the treatment and prophylaxis of postcytostatic neutropeniaПэгфилграстим в профилактике и лечении постцитостатической нейтропенииFedenkoA. A.ФеденкоА. А.
Russian Federation
fedenko@eesg.ruStroyakovskyD. L.СтрояковскийД. Л.
Russian Federation
N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical SciencesРоссийский онкологический научный центр им Н.Н. Бохина РАМН62 Oncology County Hospital62-я городская клиническая больница1106201023546211012022Copyright ©; 2010, Fedenko A.A., Stroyakovsky D.L.Copyright ©; 2010, Феденко А.А., Строяковский Д.Л.2010Fedenko A.A., Stroyakovsky D.L.Феденко А.А., Строяковский Д.Л.https://creativecommons.org/licenses/by/4.0https://sarbon.abvpress.ru/jour/article/view/173

Neutropenia is one of the most often life-threatening adverse events after cytotoxic chemotherapy. During the past two decades myeloid growth factors are used for the reducing the risk of neutripenia. Current recommendations allow routine usage of growth factors when the risk of neutropenia is more than 20%. Myeloid growth factors reduce neutropenia duration and make the possibility to give dose-dense and dose-intensive regimens in a preplanned schedule. Pegfilgrastim is a pegilated recombinant granulocyte colonystimulating factor (GCSF) with a prolonged mechanism of action. Clinical trials data showed that pegfilgrastim is more effective in decreasing of febril neutropenia comparing to filgrastim. This article reviews neutropenia and its complications and pegfilgrastin clinical experience.

Нейтропения является одним из самых частых осложнений цитостатической терапии. Для снижения риска развития нейтропенических осложнений почти два десятилетия используются миелоидные факторы роста. Современные рекомендации предполагают рутинное использование факторов роста при риске развития фебрильной нейтропении более 20%. Миелоидные факторы роста сокращают продолжительность нейтропении и позволяют проводить дозо-интенсивные и уплотненные режимы в полном объеме. Пэгфилграстим - пэгилированный рекомбинантный гранулоцитарный колониестимулирующий фактор (G-CSF) пролонгированного действия. В каждом цикле химиотерапии препарат вводится только один раз. Данные ряда исследований свидетельствуют, что пэгфилграстим не уступает филграстиму в профилактике нейтропении, но эффективнее снижает частоту фебрильной нейтропении. В обзоре рассматриваются нейтропения и ее осложнения, фармакологические свойства и опыт клинического применения пэгфилграстима.

solid tumorssarcomasneutropeniafebril neutropeniapegfilgrastimсолидные опухолисаркомынейтропенияфебрильная нейтропенияпэгфилграстимDi Maio М., Gridelli C., Gallo C. et al. Chemotherapy induced neutropenia and treatment efficacy in advanced non-small-cell lung cancer. A pooled analysis of three randomized trials. Tancet Oncol. 2005, v. 6, p. 669-677.Bergh J. Adjuvant chemotherapy for breast cancer - «one fits all»? Breast. 2005, v. 14, p. 564-569.Bodey G.P., Buckley M., Sathe Y.S., Freireich E.J. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann. Intern. Med. 1966, v. 64, p. 328-340.National Cancer Institute. Common Terminology Criteria for Adverse Events, v. 3.0. Available at: http://www.cstep. cancer.gov/forms/CTCAEv3.pdf. Accessed March 13. 2006.Hughes et al. Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer. Clin. Inf. Dis. 2002, v. 34, p. 730-751.Lyman G.H., Dale D.C., Crawford J. Incidence and pre-dictors of low dose-intensity in adjuvant breast cancer chemotherapy. A nationwide study of community practices. J. Clin. Oncol. 2003, v. 21, p. 4524-4531.Lyman G.H., Dale D.C., Friedberg J. et al. Incidence and predictors of low chemotherapy dose-intensity in aggressive non-Hodgkin’s lymphoma. A nationwide survey. J. Clin. Oncol. 2004, v. 22, p. 4302-4311.Paridaens R., Lyman G.H., Leonard R. et al. Delivering optimal adjuvant chemotherapy in primary breast cancer. The role of rHuG-CSE Eur. J. Cancer. 2003, v. 1, suppl 9.Lyman G.H., Lyman C.H., Agboola O. et al. Risk models for predicting chemotherapy-induced neutropenia. The Oncologist. 2005, v. 10, p. 427-437.National Comprehensive Cancer Network. 2005. NCCN clinical practice guidelines in oncology. Fever and neuropenia. Version 1. 2005.Bonadouna G., Valagussa P., Molitemi A. et al. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in nodepositive breast cancer. The results of 20 years of follow-up. N. Engl. J. Med. 1995, v. 332, p. 901-906.Budman D.R., Berry D.A., Cirrincione C.T. et al. Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The Cancer and Leukemia Group B. J. Natl. Cancer Inst. 1998, v. 90, p. 1205-1211.Zwick C., Gleissner B., Pfreundschuh M. Aspect of chemotherapy schedules in young and elderly patients with aggressive lymphoma. Clinical Lymphoma and Myeloma. 2007, v. 8, suppl. 2, p. 43-49.Hsieh M., Malech H. Neutrophil disorders and neutropenias. В книге The Bethesda Handbook of Clinical Hematology. Lippincott Williams & Wilkins, a Wolter Kluwer Business. 2010.Hubel K., Dale D.C., Liles W.C. Therapeutic use of cytokines to modulate phagocyte function for the treatment of infectious diseases: current status of granulocyte-macrophage colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, and interferon-gamma. J. Infect. Dis. 2002, v. 185, p. 1490-1501.Piedmonte D., Treuheit M. Formulation of Neulasta (pegfilgrastim). Advanced Drug Delivery Reviews 60. 2008, p. 50-58.Abuchowski A., van Es T., Palczuk N.C., Davis F.F. Alteration of immunological properties of bovine serum albumin by covalent attachment of polyethylene glycol, J. Biol. Chem. 1977, v. 252, p. 3578-3581.Hamidi M., Azadi A., Rafiei P. Pharmacokinetic consequences of PEGylation, Drug Deliv. 2006, v. 13, p. 399-409.Greenwald R.B. PEG drugs: an overview, J. Control Release 74 (2001) p. 159-171.Bonadonna G., Valagussa P., Molitemi A. at al. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in nodepositive breast cancer: the results of 20 years of follow-up. N. Engl. J. Med. 1995, v. 332, p. 901-906.Wood W.C., Budman D.R., Korzun A.H. et al. Dose and dose intensity of adjuvant chemotherapy for stage II, nodepositive breast carcinoma. N. Engl. J. Med. 1994, v. 330, p. 1253-1259.Budman D.R., Berry D.A., Cirrincione C.T. et al. Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The Cancer and Leukemia Group B. J. Natl. Cancer Inst. 1998, v. 90, p. 1205-1211.Martin M., Pienkowski T., Mackey J. et al. Adjuvant docetaxel for node-positive breast cancer. N. Engl. J. Med. 2005, v. 352, p. 2302-2313.Vogel C.L., Wojtukiewicz M.Z., Carroll R.R. 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, v. 23, p. 1178-1184.Holmes F.A. et al. Asingle dose of pegylated filgrastim (SD/01) is as effective as daily filgrastim for hematologic support of chemotherapy in breast cancer patients: Results of a randomized, double-blind, phase 3 trial [abstract]. American Society of Clinical Oncology Annual Meeting. 2001, p. 27.Holmes F.A., O’Shaughnessy J.A., Vukelja S. et al. Blinded, randomized, multicenter study to evaluate single administration pegfi lgrastim once per cycle versus daily filgrastim as an adjunct to chemotherapy in patients with high-risk stage II or stage III/IVbreast cancer. J. Clin. Oncol. 2002, v. 20, p. 727-731.Green M. et al. A randomized, double-blind, phase 3 study evaluating fixed-dose, once-per-cycle pegylated filgrastim (SD/01) vs daily filgrastim to support chemotherapy for breast cancer [abstract]. American Society of Clinical Oncology Annual Meeting. 2001, p. 90.Siena S., Piccart M., Holmes F.A. et al. Acombined analysis of two pivotal randomized trials of a single dose of pegfilgrastim per chemotherapy cycle and daily filgrastim in patients with stage II-IV breast cancer. Oncol. Rep. 2003, v. 10, p. 715-724.Von Minckwitz G., Blohmer J.U., Lohr A. et al. Primary prophylaxis with 3 weekly pegfilgrastim and ciprofloxacin effectively prevent (febrile) neutropenia and infection during neoadjuvant chemotherapy with docetaxel/doxorubicin/cyclophosphamide in breast cancer patients. J. Support Oncol. 2005, v. 3, suppl 2, p. 28-29.Crawford J., Ozer H., Stoller R. et al. Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N. Engl. J. Med. 1991, v. 325, p. 164-170.Trillet-Lenoir V., Green J., Manegold C., von Pawel J. et al. Recombinant granulocyte colony-stimulating factor reduces the infectious complications of cytotoxic chemotherapy. Eur. J. Cancer. 1993, v. 29A, p. 319-24.Tïmmer-Bonte J.N., de Boo T.M., Smit H.J. et al. Prevention of chemotherapy-induced febrile neutropenia by prophylactic antibiotics plus or minus granulocyte colony-stimulating factor in small-cell lung cancer: a Dutch randomized phase III study. J. Clin. Oncol. 2005, v. 23, p. 7974-7984.Pirker R., Ulsperger E., Aigner К. et al. A phase II study of pegfilgrastim to support ACE 14 chemotherapy for the treatment of subjects with small cell lung cancer. J. Support Oncol. 2005, v. 3, suppl 1, p. 44-45.Riedel R., Garst J., Dunphy F. et al. Pegfilgrastim supports dose-dense carboplatin/vinorelbine in the treatment of thoracic malignancies. J. Support Oncol. 2004, v. 2, suppl 2, p. 58-59.Spunt S., Irving H., Frost J. et al. Phase II, Randomized, Open-Label Study of Pegfilgrastim-Supported VDC/IE Chemotherapy in Pediatric Sarcoma Patients. Journal of Clinical Oncology. 2010, v. 28, No 8 (March 10), p. 1329-1336.Campos L.T., Folbe M., Charu V. et al. Frequency of neutropenia-related events during chemotherapy and the use of pegfilgrastim and filgrastim in community practice. Results of the ACCEPT study. J. Support Oncol. 2005, v. 3, suppl 2, p. 44-45.Kloess M., Zeynalova S., Truemper L. et al. Effects of G-CSF schedule on leukocyte recovery and infection rate in the CHOP-14 regimen for elderly patients with aggressive lymphoma. Poster presented at the 39th Annual Meeting of the American Society of Clinical Oncology; May 31 - June 3,2003; Chicago, 111. Abstract 2402.Weycker D., Hackett J., Edelsberg J.S. et al. Are shorter courses of filgrastim prophylaxis associated with increased risk of hospitalization? Ann Pharmacother. 2006, v. 40, p. 402-407.Smith T.J., Khatcheressian J., Lyman G.H. et al. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J. Clin. Oncol. 2006, v. 24, p. 3187-3205.Aapro M.S., Cameron D.A., Pettengell R. et al. EORLC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphomas and solid tumours. Eur. J. Cancer. 2006, v. 42, p. 2433-2453.National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Myeloid Growth Factors. V. 1. 2006. http://www.nccn.org/professionals/physiciangls/PDF/myeloid growth.pdf.Greil R., Jost L.M. ESMO recommendations for the application of hematopoietic growth factors. Ann. Oncol. 2005, V. 16, suppl 1, p. 80-82.American Society of Clinical Oncology. Recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines. J. Clin. Oncol. 1994, v. 12, p. 2471-508.American Society of Clinical Oncology. Update of recommendations for the use of hematopoietic colony-stimulating factors: evidence-based clinical practice guidelines. J. Clin. Oncol. 1996, v. 14, p. 1957-1960.Ozer H., Armitage J.O., Bennett C.L. et al. Update of recommendations for the use of hematopoietic colonystimulating factors: evidence-based, clinical practice guidelines. J. Clin. Oncol. 2000, v. 18, p. 3558-3585.Lyman G.H., Kuderer N., Greene J., Balducci L. Lheeconomics of febrile neutropenia: implications for the use of colony-stimulating factors. Eur. J. Cancer. 1998, Nov., v. 34 (12), p. 1857-1864.Lyman G.H. Balancing the benefits and costs of colony-stimulating factors: a current perspective. Semin Oncol. 2003, v. 30, 4 suppl 13, p.10-17.Lyman G.H., Kuderer N.M. The economics of thecolony-stimulating factors in the prevention and treatment of febrile neutropenia. Crit. Rev. Oncol. Hematol. 2004, v. 50, p. 129-146.Calhoun E.A., Schumock G.L., McKoy J.M. et al. Granulocyte colony-stimulating factor for chemotherapy-induced neutropenia in patients with small cell lung cancer: the 40% rule revisited. Pharmacoeconomics. 2005, v. 23, p. 767-775.