Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Supportive Care in Cancer
Published in: Supportive Care in Cancer 11/2008

Open Access 01-11-2008 | Original Article

Neutropenia occurrence and predictors of reduced chemotherapy delivery: results from the INC-EU prospective observational European neutropenia study

Authors: Ruth Pettengell, Matthias Schwenkglenks, Robert Leonard, André Bosly, Robert Paridaens, Manuel Constenla, Thomas D. Szucs, Christian Jackisch, Impact of Neutropenia in Chemotherapy—European Study Group (INC-EU)

Published in: Supportive Care in Cancer | Issue 11/2008

Login to get access

Abstract

Goals of work

Neutropenia is a life-threatening, dose-limiting toxicity of many chemotherapy regimens. The goals of this study were to assess the incidence and risk of chemotherapy-induced neutropenia, febrile neutropenia (FN) and dose limitations in breast cancer and lymphoma patients undergoing chemotherapy in Europe.

Patients and methods

Four hundred forty-four breast cancer and 305 lymphoma patients undergoing chemotherapy at 66 practices in five European countries participated in this prospective, observational study. Predictors of impaired chemotherapy delivery were investigated using a logistic regression model.

Main results

In breast cancer, FN incidence was low (6%); however, grade 4 neutropenia was frequent (34%). Lymphoma patients experienced higher incidences of FN (non-Hodgkin lymphoma (NHL) 22%; Hodgkin lymphoma (HL) 15%) and grade 4 neutropenia (NHL 54%; HL 40%). For both diseases, FN and grade 4 neutropenia were associated with low relative dose intensity (RDI). Multivariate regression models indicated that first cycle FN, age ≥ 65 years and Eastern Co-operative Oncology Group > 1 were associated with low RDI in breast cancer and lymphoma, while colony-stimulating factor (CSF) primary prophylaxis appeared to be protective in lymphoma only. Primary CSF prophylaxis was provided to 9% of breast cancer, 28% of NHL and 19% of HL patients.

Conclusions

Neutropenia and low RDI remain serious problems in both breast cancer and lymphoma populations undergoing chemotherapy. Several risk factors which can trigger reduced chemotherapy delivery were identified. These results can support physicians in identifying patients most at risk of receiving impaired chemotherapy delivery who would benefit from suitable preventive measures.
Literature
1.
Aapro MS, Cameron DA, Pettengell R, Bohlius J, Crawford J, Ellis M, Kearney N, Lyman GH, Tjan-Heijnen VC, Walewski J, Weber DC, Zielinski C (2006) EORTC 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 42:2433–2453PubMedCrossRef
2.
Bonadonna G, Valagussa P, Moliterni A, Zambetti M, Brambilla C (1995) Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med 332:901–906PubMedCrossRef
3.
Bosly A, Bron D, Van Hoof A, De Bock R, Berneman Z, Ferrant A, Kaufman L, Dauwe M, Verhoef G (2008) Achievement of optimal average relative dose intensity and correlation with survival in diffuse large B-cell lymphoma patients treated with CHOP. Ann Hematol, online advance access DOI 10.​1007/​s00277-007-0399-y
4.
Budman DR, Berry DA, Cirrincione CT, Henderson IC, Wood WC, Weiss RB, Ferree CR, Muss HB, Green MR, Norton L, Frei E3 (1998) 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 90:1205–1211PubMedCrossRef
5.
Chirivella I, Bermejo B, Insa A, Perez-Fidalgo A, Magro A, Rosello E, Garcia-Garre E, Martin P, Bosch A, Lluch A (2006) Impact of chemotherapy dose-related factors on survival in breast cancer patients treated with adjuvant anthracycline-based chemotherapy. J Clin Oncol 24:44s (Abs 668)CrossRef
6.
Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Gisselbrecht C (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:235–242PubMedCrossRef
7.
Crawford J, Ozer H, Stoller R, Johnson D, Lyman G, Tabbara I, Kris M, Grous J, Picozzi V, Rausch G et al (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 325:164–170PubMedCrossRef
8.
Crawford J, Dale DC, Lyman GH (2004) Chemotherapy-induced neutropenia: risks, consequences, and new directions for its management. Cancer 100:228–237PubMedCrossRef
9.
Crawford J, Wolff DA, Culakova E, Poniewierski MS, Selby C, Dale DC, Lyman GH (2004) First cycle risk of severe and febrile neutropenia in cancer patients receiving systemic chemotherapy: results from a prospective nationwide study. Blood 104:Abs 2210CrossRef
10.
Dale DC, McCarter GC, Crawford J, Lyman GH (2003) Myelotoxicity and dose intensity of chemotherapy: reporting practices from randomized clinical trials. J Natl Compr Canc Netw 1:440–454PubMed
11.
Diehl V, Franklin J, Pfreundschuh M, Lathan B, Paulus U, Hasenclever D, Tesch H, Herrmann R, Dorken B, Muller-Hermelink HK, Duhmke E, Loeffler M (2003) Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin’s disease. N Engl J Med 348:2386–2395PubMedCrossRef
12.
Kuderer NM, Dale DC, Crawford J, Cosler LE, Lyman GH (2006) Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer 106:2258–2266PubMedCrossRef
13.
Kwak LW, Halpern J, Olshen RA, Horning SJ (1990) Prognostic significance of actual dose intensity in diffuse large-cell lymphoma: results of a tree-structured survival analysis. J Clin Oncol 8:963–977PubMed
14.
Leonard RC, Miles D, Thomas R, Nussey F (2003) Impact of neutropenia on delivering planned adjuvant chemotherapy: UK audit of primary breast cancer patients. Br J Cancer 89:2062–2068PubMedCrossRef
15.
Lyman GH, Dale DC, Crawford J (2003) Incidence and predictors of low dose-intensity in adjuvant breast cancer chemotherapy: a nationwide study of community practices. J Clin Oncol 21:4524–4531PubMedCrossRef
16.
Lyman GH, Morrison VA, Dale DC, Crawford J, Delgado DJ, Fridman M (2003) Risk of febrile neutropenia among patients with intermediate-grade non-Hodgkin’s lymphoma receiving CHOP chemotherapy. Leuk Lymphoma 44:2069–2076PubMedCrossRef
17.
Lyman GH, Dale DC, Friedberg J, Crawford J, Fisher RI (2004) Incidence and predictors of low chemotherapy dose-intensity in aggressive non-Hodgkin’s lymphoma: a nationwide study. J Clin Oncol 22:4302–4311PubMedCrossRef
18.
Lyman GH, Lyman CH, Agboola O (2005) Risk models for predicting chemotherapy-induced neutropenia. Oncologist 10:427–437PubMedCrossRef
19.
Lyman GH, Kuderer NM, Poniewierksi MS, Crawford J, Wolff DA, Culakova E, Dale DC, Lyman GH, Kuderer NM, Poniewierksi MS, Crawford J, Wolff DA, Culakova E, Dale DC (2007) Factors associated with reductions in chemotherapy dose intensity: impact of clinical, sociodemographic and practice setting. J Clin Oncol 25:Abs 6550CrossRef
20.
Martin M, Lluch A, Segui MA, Ruiz A, Ramos M, Adrover E, Rodriguez-Lescure A, Grosse R, Calvo L, Fernandez-Chacon C, Roset M, Anton A, Isla D, Del Prado PM, Iglesias L, Zaluski J, Arcusa A, Lopez-Vega JM, Munoz M, Mel JR (2006) Toxicity and health-related quality of life in breast cancer patients receiving adjuvant docetaxel, doxorubicin, cyclophosphamide (TAC) or 5-fluorouracil, doxorubicin and cyclophosphamide (FAC): impact of adding primary prophylactic granulocyte-colony stimulating factor to the TAC regimen. Ann Oncol 17:1205–1212PubMedCrossRef
21.
22.
23.
NICE (2006) Docetaxol for the adjuvant treatment of early node-positive breast cancer. NICE Technology Appraisal Guidance 109:1–21
24.
Nijhuis CO, Kamps WA, Daenen SM, Gietema JA, van der Graaf WT, Groen HJ, Vellenga E, Ten Vergert EM, Vermeulen KM, de Vries-Hospers HG, de Bont ES (2005) Feasibility of withholding antibiotics in selected febrile neutropenic cancer patients. J Clin Oncol 20(23):7437–7444CrossRef
25.
Pettengell R, Gurney H, Radford JA, Deakin DP, James R, Wilkinson PM, Kane K, Bentley J, Crowther D (1992) Granulocyte colony-stimulating factor to prevent dose-limiting neutropenia in non-Hodgkin’s lymphoma: a randomized controlled trial. Blood 80:1430–1436PubMed
26.
Pfreundschuh M, Trumper L, Kloess M, Schmits R, Feller AC, Rube C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M, The German High-Grade Non-Hodgkin’s Lymphoma Study G (2004) Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood 104:634–641PubMedCrossRef
27.
Pfreundschuh M, Trumper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rube C, Loeffler M, The German High-Grade Non-Hodgkin’s Lymphoma Study G (2004) Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood 104:626–633PubMedCrossRef
28.
Repetto L, Accettura C (2003) The importance of prophylactic management of chemotherapy-induced neutropenia. Anticancer Drugs 14:725–730PubMedCrossRef
29.
Repetto L, Biganzoli L, Koehne CH, Luebbe AS, Soubeyran P, Tjan-Heijnen VC, Aapro MS (2003) EORTC Cancer in the Elderly Task Force guidelines for the use of colony-stimulating factors in elderly patients with cancer. Eur J Cancer 39:2264–2272PubMedCrossRef
30.
Schwenkglenks M, Jackisch C, Constenla M, Kerger JN, Paridaens R, Auerbach L, Bosly A, Pettengell R, Szucs TD, Leonard R (2006) Neutropenic event risk and impaired chemotherapy delivery in six European audits of breast cancer treatment. Support Care Cancer 14:901–909PubMedCrossRef
31.
Sehn LH, Connors JM (2005) Treatment of aggressive non-Hodgkin’s lymphoma: a north American perspective. Oncology 19:26–34PubMed
32.
Shayne M, Crawford J, Dale DC, Culakova E, Lyman GH (2006) Predictors of reduced dose intensity in patients with early-stage breast cancer receiving adjuvant chemotherapy. Breast Cancer Res Treat 100:255–262PubMedCrossRef
33.
Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, Bennett CL, Cantor SB, Crawford J, Cross SJ, Demetri G, Desch CE, Pizzo PA, Schiffer CA, Schwartzberg L, Somerfield MR, Somlo G, Wade JC, Wade JL, Winn RJ, Wozniak AJ, Wolff AC (2006) 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 24:3187–3205PubMedCrossRef
34.
Trudeau M, Charbonneau F, Gelmon K, Laing K, Latreille J, Mackey J, McLeod D, Pritchard K, Provencher L, Verma S (2005) Selection of adjuvant chemotherapy for treatment of node-positive breast cancer. Lancet Oncol 6:886–898PubMedCrossRef
Metadata
Title
Neutropenia occurrence and predictors of reduced chemotherapy delivery: results from the INC-EU prospective observational European neutropenia study
Authors
Ruth Pettengell
Matthias Schwenkglenks
Robert Leonard
André Bosly
Robert Paridaens
Manuel Constenla
Thomas D. Szucs
Christian Jackisch
Impact of Neutropenia in Chemotherapy—European Study Group (INC-EU)
Publication date
01-11-2008
Publisher
Springer-Verlag
Published in
Supportive Care in Cancer / Issue 11/2008
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-008-0430-4

Other articles of this Issue 11/2008

Supportive Care in Cancer 11/2008 Go to the issue

Short Communication

Osteonecrosis of the jaw (ONJ) in cancer patients treated with Bisphosphonates: how the knowledge of a phenomenon can change its evolution

Original Article

Maintenance of effects of a home-based physical activity program among breast cancer survivors

Review Article

A review of patient self-report tools for chemotherapy-induced nausea and vomiting

Original Article

Noncancer life stresses in newly diagnosed cancer

Original Article

Comfort in the last 2 weeks of life: relationship to accessing palliative care services

Original Article

Mirtazapine improves sleep and lowers anxiety and depression in cancer patients: superiority over imipramine
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits