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Curr Oncol. 2010 April; 17(2): 2–3.
PMCID: PMC2854631

Febrile neutropenia rates with adjuvant docetaxel and cyclophosphamide chemotherapy in early breast cancer: discrepancy between published reports and community practice—a retrospective analysis


Adjuvant therapies, including chemotherapy, are a major reason for the improved survival in early breast cancer in North America and Europe. As treatments have become more successful, the indications have expanded to include cancers in node-negative and in older women 1,2. Recent clinical trials have largely supported the additional benefit of taxane therapy, including benefit in older patients 3.

The increase in the proportion of women treated and the improved survival mean that toxicities become increasingly important. One of the most serious acute toxicities is febrile neutropenia (fn). A newer report has demonstrated the benefit for disease-free and overall survival of 4 cycles of docetaxel–cyclophosphamide (tc) chemotherapy over doxorubicin–cyclophosphamide chemotherapy and has also reported acceptable toxicity with a fn rate of 5% 4. The tc regimen has become very popular in Ontario, particularly in older age groups who are at increased risk of cardiotoxicity with anthracyclines, or in those eligible for trastuzumab 5.

Here, we share our preliminary experience at the London Regional Cancer Program with fn incidence related to the use of tc chemotherapy in the adjuvant setting.


This short report is based on a consecutive series of 39 patients treated with 4 cycles of tc from January 2008 to May 2009 and assessed by retrospective chart review as a quality assurance tool. The final review was done June 17, 2009.

These women all had early-stage (high-risk node-negative, node-positive, or T1, 2, or 3, but not locally advanced or inflammatory) breast cancer and were treated with docetaxel 75 mg/m2 plus cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles. All patients were evaluable for review and analysis after completion of the prescribed treatment (admissions may have been at our host hospital or at a community hospital) and include those who stopped treatment early. Medical records for all hospitals in the region but one are available via electronic health record, and all discharge summaries were available for patients admitted with fn. Our institution defines fn as a temperature of 38.0°C, for which patients are instructed to seek emergency medical assessment, including clinical assessment and complete blood count, by a physician. The standard definition of neutropenia is a cell count below 0.5×109/L (or below 1.0×109/L and expected to worsen).


In this group of patients, median age was 65 years (range: 39–84 ywears). Comorbidities were present in 12 patients (4 diabetes mellitus, 2 pulmonary embolism, 3 prior chemotherapy, and 1 each Crohn disease, sleep apnea, and delayed wound healing), and 11 patients had received primary prophylaxis with filgrastim or pegylated filgrastim. Three patients were unable to complete treatment, and none were lost to follow up. Table i summarizes the fn rate in these patients by subgroup.

Age group, comorbidities, use of granulocyte colony–stimulating factor (g-csf) and incidence of febrile neutropenia (fn)

The fn rate was 33% (13/39) across all patients. Patients 65 years of age and older had a documented fn rate of 40% (8/20). One of the 3 patients that stopped treatment early had fn. Of the 11 patients that received primary prophylaxis, none experienced fn, despite risk factors of older age and comorbid conditions in 2, older age in another 3, and comorbidity in another 2. For patients not receiving primary prophylaxis, the fn rate was 46% (13/28); in patients older than 65 years with comorbidities not receiving primary prophylaxis, it was 100% (5/5).


Based on these limited observations, it appears that tc chemotherapy is associated with a higher fn rate than has been published or reported. No patients died or required intensive care as a result of fn complications. Our rate may be a result of treatment of a population older or with more comorbidities than is usually entered into a clinical trial, which is consistent with risk factors from the National Comprehensive Cancer Network and the American Society of Clinical Oncology guidelines 6,7.

We used age 65 as a benchmark because our provincial government health insurance does not cover supportive care drug costs for outpatients younger than 65 years of age and also because age 65 is considered a risk factor for fn. Interestingly, the risk of fn also seems high in the younger group. The average age on the U.S. oncology trial was 52 years as compared with 67 years in our cohort. We also suspect that primary prophylaxis is underreported. The initial report of tc 8 did not mention whether primary prophylaxis was used; the subsequent report indicated that prophylactic quinolones were recommended (but not required) and did not mention how many patients were given prophylactic antibiotics.

We feel that age, comorbidities such as diabetes 9, and less-routine use of prophylaxis are significant factors increasing the risk of fn. Although primary prophylaxis with granulocyte colony–stimulating factor has little effect on mortality from fn 10, our experience should serve to encourage more consistent and complete reporting of supportive care drugs and comorbidities when assessing the toxicities of adjuvant chemotherapy. Our rate of fn, if confirmed by studies in larger patient cohorts, would argue for a greater role for primary prophylaxis.


1. Clarke M, Coates AS, Darby SC, on behalf of the Early Breast Cancer Trialists’ Collaborative Group (ebctcg) Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer: patient-level meta-analysis of randomised trials. Lancet. 2008;371:29–40. [PubMed]
2. Muss HB, Woolf S, Berry D, on behalf of the Cancer and Leukemia Group B Adjuvant chemotherapy in older and younger women with lymph node–positive breast cancer. JAMA. 2005;293:1073–81. [PubMed]
3. De Laurentiis M, Cancello G, D’Agostino D. Taxanebased combinations as adjuvant chemotherapy of early breast cancer: a meta-analysis of randomized trials. J Clin Oncol. 2008;26:44–53. [PubMed]
4. Jones S, Holmes FA, O’Shaughnessy J. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of U.S. Oncology Research Trial 9735. J Clin Oncol. 2009;27:1177–83. [PubMed]
5. Cancer Care Ontario (cco) and Action Cancer Ontario (aco) Toronto, ON: CCO and ACO; 2009. Emergency department visits after adjuvant chemotherapy [Web page] [Available at:; cited August 18, 2009]
6. National Comprehensive Cancer Network (nccn) NCCN Clinical Practice Guidelines in Oncology: Myeloid Growth Factors V.1.2010. Fort Washington, PA: NCCN; 2010. [Available online at: (registration required); cited February 19, 2010]
7. Smith TJ, Khatcheressian J, Lyman GH. 2006 Update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol. 2006;24:3187–205. [Available online at:; cited June 9, 2009] [PubMed]
8. Jones SE, Savin MA, Holmes FA. Phase iii trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol. 2006;24:5381–7. [PubMed]
9. Srokowski TP, Fang S, Hortobagyi GN, Giordano SH. Impact of diabetes mellitus on complications and outcomes of adjuvant chemotherapy in older patients with breast cancer. J Clin Oncol. 2009;27:2170–6. [PMC free article] [PubMed]
10. Sung L, Nathan PC, Alibhai SM, Tomlinson GA, Beyene J. Meta-analysis: effect of prophylactic hematopoietic colony-stimulating factors on mortality and outcomes of infection. Ann Intern Med. 2007;147:400–11. [PubMed]

Articles from Current Oncology are provided here courtesy of Multimed Inc.