The comparison of the preventive effects of filgrastim and lenograstim in pediatric cancer patients treated with chemotherapy and radiotherapy

Abstract

OBJECTIVES To compare the preventive effects of filgrastim and lenograstim in pediatric cancer patients treated with chemotherapy and radiotherapy. METHODS Eighty-two patients treated with myelosuppressive chemotherapy and/or radiotherapy in Pediatric Oncology and Radiation Oncology Departments of Kocaeli University, Faculty of Medicine between September 2005 and March 2007 were randomized to filgrastim and lenograstim arms. Radiotherapy doses and fields 3 weeks prior to the therapy, age, gender, histopathological type of the tumor, stage and chemotherapy protocols were recorded. Patients with bone marrow infiltration due to the tumoral invasion and patients receiving steroid including chemotherapy regimens were excluded from the study. Equivalent doses of two hematopoetic growth factors (filgrastim 5 μg/ kg/ day, S.C; lenograstim 150 μg/ m2/ day, S.C) were applied beginning 24 hours following the completion of the chemotherapy till leukocyte count reached 10.000/mm3. RESULTS Delay in the new chemotherapy cure following chemotherapy protocol was median 5 days in lenograstim arm (16 patients, 37%) while it was 3 days in filgrastim arm (10 patients; %25) however the difference was not statistically significant (p=0.188). In lenogastrim arm, febrile neutropenia occurred in 6 patients and infections without neutropenia were seen in 4 patients (pneumonia in 2 patients, otitis media in 1 patient and pharengitis in 1 patient). In filgrastim arm, febrile neutropenia occurred in 3 patients and gingivitis and gastroenteritis in 2 patients and the difference between two groups was also not significant (p=0.258). However, bone pain was present in 2 patients in lenograstim arm while it was seen in 10 patients in filgrastim arm with a significant difference (p=0.008). CONCLUSION Although preventive effects of filgrastim and lenograstim on febrile neutropenia and non-neutropenic infections in patients receiving radiotherapy and chemotherapy are not significantly different, delay in the new chemotherapy cure following chemotherapy protocol is shorter in filgrastim arm. However, bone pain is also significantly higher in filgrastim arm.

Keywords

• Chemotherapy,Radiotherapy,Hematopoietic Cell Growth Factors,Neutropenia,Filgrastim,lenograstim

Kemoterapi ve radyoterapi uygulanan kanserli çocuklarda nötropeninin önlenmesinde filgrastim ve lenograstim'in etkinliklerinin karşılaştırılması

Abstract

AMAÇ Kemoterapi (KT) ve radyoterapi ( RT) sırasında veya sonrasında kullanılan iki farklı hematopoetik büyüme faktörünün nötropeni ciddiyeti ve süresini azaltma üzerindeki etkinliği değerlendirildi. GEREÇ VE YÖNTEM Eylül 2005-Mart 2007 tarihleri arasında Kocaeli Üniversitesi Çocuk Onkoloji Bilim Dalı ve Radyasyon Onkolojisi Anabilim Dallarında kanser tanısı ile miyelosupresif KT ve/veya RT uygulanan toplam 82 hasta başvuru sıralarına göre filgrastim veya lenograstim koluna randomize edildiler. Çalışmaya dâhil edilmeden önceki 3 hafta içinde uygulanmış olan RT doz ve alanları, yaş, cinsiyet, tümör tipi, evresi ve uygulanan KT protokolleri kaydedildi. Primer malignitesine bağlı kemik iliği disfonksiyonu olanlar ve KT protokolü kapsamında steroid uygulananlar çalışma dışı bırakıldı. Her iki hemopoetik büyüme faktörü (HBF) eşdeğer dozlarda (filgrastim 5 μgr/kg/gün, S.C. ve lenograstim 150 μgr/m2/ gün, S.C), KT bitiminden 24 saat sonra başlanarak lökosit sayısı 10.000/ mm3 olana dek uygulandı. BULGULAR Lenograstim uygulanan 16 hastada (%37.2) yeni KT küründe gecikme süresi ort. 5 gün olarak saptanırken, filgrastim uygulanan grupta gecikme daha azdı (10 hasta; %25.6 ve ort. 3 gün) fakat bu fark anlamlı bulunmadı (p=0.188). Lenograstim uygulanan 6 hastada febril nötropeni ve 4 hastada nötropenik olmayan enfeksiyon atağı (2 atakta pnomoni, 1 atakta otit ve 1 atakta farenjit), filgrastim uygulananlarda ise 3 hastada febril nötropeni, 2 hastada ise gingivit ve gastroenterit olmak üzere febril nötropenik olmayan atak gözlendi. İki grup arasında enfeksiyon sıklığı yönünden farklılık saptanmadı (p=0.258). Lenograstim alan grupta 2 hastada belirgin yan etki olarak kemik ağrısı saptandı. Bununla birlikte filgrastim uygulanan grupta ise 10 hastada kemik ağrısı belirlendi ( p= 0.008). SONUÇ RT ve KT uygulanan hastalarda, tedaviye bağlı nötropeninin ve nötropenik olmayan enfeksiyonların önlenmesinde lenograstim ve filgrastim'in etkinlikleri arasında anlamlı bir farklılık bulunmamaktadır. Filgrastim alanlarda yeni KT sikluslarının başlanmasındaki gecikme daha azdır; filgrastim uygulamasına bağlı kemik ağrısı, lenograstim alanlara göre daha sık görülmektedir.

Keywords

• Büyüme faktörleri, enfeksiyon, febril nötropeni, kemoterapi, radyoterapi

References

1. 1. Kubota N, Orita T, Hattori K, Oh-eda M, Ochi N, Yamazaki T. Structural characterization of natural and recombinant human granulocyte colony-stimulating factors. J Biochem (Tokyo) 1990;107(3):486-92.
2. 2. Dunn CJ, Goa KL. Lenograstim: an update of its pharmacological properties and use in chemotherapyinduced neutropenia and related clinical settings. Drugs 2000;59(3):681-717.
3. 3. Weisbart RH, Gasson JC, Golde DW. Colony-stimulating factors and host defense. Ann Intern Med 1989;110(4):297-303.
4. 4. Metcalf D. The molecular biology and functions of the granulocyte-macrophage colony-stimulating factors. Blood 1986;67(2):257-67.
5. 5. Xaus J, Comalada M, Valledor AF, Cardó M, Herrero C, Soler C, et al. Molecular mechanisms involved in macrophage survival, proliferation, activation or apoptosis. Immunobiology 2001;204(5):543-50.
6. 6. Hays SJ. Therapeutic approaches to the treatment of neuroinflammatory diseases. Curr Pharm Des 1998;4(4):335-48.
7. 7. Coppack SW. Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc 2001;60(3):349-56.
8. 8. Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, 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;24(19):3187-205.

9. 9. Vogel CL, Wojtukiewicz MZ, Carroll RR, Tjulandin SA, Barajas-Figueroa LJ, Wiens BL, 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(6):1178-84.
10. 10. Timmer-Bonte JN, de Boo TM, Smit HJ, Biesma B, Wilschut FA, Cheragwandi SA, et al. Prevention of chemotherapy-induced febrile neutropenia by prophylactic antibiotics plus or minus granulocyte colonystimulating factor in small-cell lung cancer: a Dutch Randomized Phase III Study. J Clin Oncol 2005;23(31):7974-84.
11. 11. Cosler LE, Eldar-Lissai A, Culakova E, Kuderer NM, Dale D, Crawford J, et al. Therapeutic use of granulocyte colony-stimulating factors for established febrile neutropenia: effect on costs from a hospital perspective. Pharmacoeconomics 2007;25(4):343-51.
12. 12. Thatcher N, Girling DJ, Hopwood P, Sambrook RJ, Qian W, Stephens RJ. Improving survival without reducing quality of life in small-cell lung cancer patients by increasing the dose-intensity of chemotherapy with granulocyte colony-stimulating factor support: results of a British Medical Research Council Multicenter Randomized Trial. Medical Research Council Lung Cancer Working Party. J Clin Oncol 2000;18(2):395-404.
13. 13.Berghmans T, Paesmans M, Lafitte JJ, Mascaux C, Meert AP, Jacquy C, et al. Therapeutic use of granulocyte and granulocyte-macrophage colony-stimulating factors in febrile neutropenic cancer patients. A systematic review of the literature with meta-analysis. Support Care Cancer 2002;10(3):181-8.
14. 14.Clark OA, Lyman GH, Castro AA, Clark LG, Djulbegovic B. Colony-stimulating factors for chemotherapy-induced febrile neutropenia: a metaanalysis of randomized controlled trials. J Clin Oncol 2005;23(18):4198-214.
15. 15. García-Carbonero R, Mayordomo JI, Tornamira MV, López-Brea M, Rueda A, Guillem V, et al. Granulocyte colony-stimulating factor in the treatment of high-risk febrile neutropenia: a multicenter randomized trial. J Natl Cancer Inst 2001;93(1):31-8.
16. 16. Malik I, Hussain M, Yousuf H. Clinical characteristics and therapeutic outcome of patients with febrile neutropenia who present in shock: need for better strategies. J Infect 2001;42(2):120-5.
17. 17. Darmon M, Azoulay E, Alberti C, Fieux F, Moreau D, Le Gall JR, et al. Impact of neutropenia duration on short-term mortality in neutropenic critically ill cancer patients. Intensive Care Med 2002;28(12):1775-80.