The use of G-CSF after the administration of chemotherapy may be in several settings:
- “Primary prophylaxis,” when neutropenia is expected to occur following a course of chemotherapy, but the patient has never experienced it.
- “Secondary prophylaxis,” when the patient had a neutropenic fever in a previous course of similar chemotherapy and is thus expected to do so again.
- “Supportive” in the attempt to shorten the duration of severe chemotherapy-induced neutropenia in patients without fever (“afebrile neutropenia”).(Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52:e56–e93. ).
Administration of G-CSF is generally not recommended for routine treatment in patients with established fever and neutropenia.
NCCN, ASCO and ASH guidelines recommend routine use of Neulasta® or Neupogen (filgrastim) for patients with an overall risk of FN of 20% or greater. Previous studies have suggested that prophylactic Neulasta can reduce the incidence of hospitalizations, decrease FN and allow better delivery of protocol doses of chemotherapy. The recommended dosage of Neulasta® is a single subcutaneous injection of 6 mg administered once per chemotherapy cycle. Neulasta® should not be administered in the period between 14 days before and 24 hours after administration of cytotoxic chemotherapy.
The supportive data was generated from 8 randomized clinical trials and 3 observational studies conducted between 1998 and 2005.
NCCN, Supportive Chemotherapy 2017
Thomas J. Smith, Kari Bohlke, Gary H. Lyman, Kenneth R. Carson, Jeffrey Crawford, Scott J. Cross, Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. Journal of Clinical Oncology 33, no. 28 (October 2015) 3199-3212.
Lyman GH, Kleiner JM. Summary and comparison of myeloid growth factor guidelines in patients receiving cancer chemotherapy. Cancer Treat Res. 2011;157:145-65.
Some specific regimens.
The reported rates of febrile neutropenia differ between studies of the TC(Taxotere/Cytoxan) studies. The Jones et al study, noted a trend toward more febrile neutropenia (FN; 5% v 2.5%, P = .07) in the TC group. A 2009 study(Soong et al) reported FN rates of up to 50%. While true rates of FN are beign assessed, I consider Neulasta appropriate for the TC regimen.
A recent study(Vandenberg et al) found that patients older than 65 had a 40% risk of febrile neutropenia with the AC regimen.
Carboplatin/paclitaxel result in a very low incidence of grade 4 neutropenia (Markman 2004)
The recent 2005 ASCO guideline added that patients treated with palliative intent for metastatic disease should have thir dose reduced rather than use myeloid growth factors.
Désirée Caselli et al,Biosimilars in the management of neutropenia: focus on filgrastim.Biologics. 2016; 10: 1722.
Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52:e56e93.
Christopher R. Flowers, Jerome Seidenfeld, Eric J. Bow, Clare Karten, Charise Gleason, Douglas K. Hawley, Nicole M. Kuderer, Amelia A. Langston, Kieren A. Marr, Kenneth V.I. Rolston and Scott D. Ramsey Antimicrobial Prophylaxis and Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology Clinical Practice Guidelin JCO January 14, 2013
Thomas J. Smith, Kari Bohlke, Gary H. Lyman, Kenneth R. Carson, Jeffrey Crawford, Scott J. Cross, John M. Goldberg, James L. Khatcheressian, Natasha B. Leighl, Cheryl L. Perkins, George Somlo, James L. Wade, Antoinette J. Wozniak and James O. Armitage, Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. JCO July 13, 2015
NCCN Supportive Care, Neutropenia, 2016.
Management of febrile neutropenia: ESMO Clinical Practice Guidelines Ann Oncol (2010) 21 (suppl 5): v252-v256.
Clark OAC, Lyman G, Castro AA, Clark LGO, Djulbegovic B. Colony stimulating factors for chemotherapy induced febrile neutropenia. Cochrane Database of Systematic Reviews 2000, Issue 4. Art. No.: CD003039
Adams, Jared R., Angelotta, Cara, Bennett, Charles L.
When the Risk of Febrile Neutropenia Is 20%, Prophylactic Colony-Stimulating Factor Use Is Clinically Effective, but Is It Cost-Effective? J Clin Oncol 2006 24: 2975-2977
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 24:3187-3205, 2006
Lyman GH: Guidelines of the National Comprehensive Cancer Network on the use of myeloid growth factors with cancer chemotherapy: A review of the evidence. J Natl Compr Canc Netw 3:557-571, 2005
D. Soong et al, High Rate of Febrile Neutropenia in Patients With Operable Breast Cancer Receiving Docetaxel and Cyclophosphamide, JCO September 10, 2009 vol. 27 no. 26 e101-e102
T. Vandenberg, BA MD, J. Younus, MD, and S. Al-Khayyat, MD Febrile neutropenia rates with adjuvant docetaxel and cyclophosphamide chemotherapy in early breast cancer: discrepancy between published reports and community practice—a retrospective analysis, Curr Oncol. 2010 April; 17(2): 2–3.
Alimta and carboplatin in second line studies have a risk of febrile neutropenia of 2.7-3.4%.
Ardizzoni A, Tiseo M, Boni L, et al: Pemetrexed versus pemetrexed and carboplatin as second-line chemotherapy in advanced nonsmall-cell lung cancer (NSCLC): Results of GOIRC 02-2006 randomized phase II study and pooled analysis with NVALT7 trial. J Clin Oncol 30:4501-4507, 2012.
2. Smit EF, Burgers SA, Biesma B, et al: Randomized phase II and pharmacogenetic study of pemetrexed compared with pemetrexed plus carboplatin in pretreated patients with advanced nonsmall-cell lung cancer.
The prevalence of febrile neutropenia in this regimen was specifically looked at from a regulatory perspective. Historically, reported rates of FN without prophylactic G-CSF range from 5% in the phase III trial to as high as 50% in retrospective chart reviews for TC regimen. Guidelines recommend GCSF propjylaxis when febrile neutropenia exceeds 20%. As G-CSF was not covered by Ontario provincial cancer funding agency for primary prophylaxis of FN with TC chemotherapy, local investigators sought to determine the incidence of FN with TC chemotherapy in two comprehensive cancer centres in Ontario, Canada. Methods: Patients who received adjuvant TC chemotherapy between January 1, 2008 and December 31, 2012 were identified through the pharmacy databases. Electronic charts were retrospectively reviewed to abstract patient characteristics, treatment details including G-CSF use, and incidence of FN. : Preliminary results from one institution demonstrate that 187 patients were treated with TC over the study period. Of the 74 (40%) patients who did not receive primary G-CSF prophylaxis, 23 (31%) developed FN requiring hospitalization and treatment with intravenous antibiotics. However, none of the 113 patients who received primary G-CSF prophylaxis (funded by the patient or a third party payer) developed FN. Putative risk factors for FN in the absence of G-CSF including age, BSA, BMI, and pre-treatment absolute neutrophil count were examined and will be reported. Conclusions: The FN rate associated with TC chemotherapy exceeds 30%, higher than that reported in the clinical trial. They concluded: As per ASCO guidelines, primary G-CSF prophylaxis should be given with TC chemotherapy, and in Canada this should be covered by provincial cancer funding agencies.
Joanne Linda Yu, Michael Kurin, Mark Pasetka, Srikala S. Sridhar, Ellen Warner; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada; Odette Cancer Centre, Sunnybrook Health Sciences Centre; University of Toronto, Toronto, ON, Canada; Princess Margaret Hospital, Toronto, ON, Canada, Febrile neutropenia with adjuvant docetaxel and cyclophosphamide (TC) chemotherapy for breast cancer. Clin Oncol 31, 2013 (suppl; abstr e17523)
Foforinox had a febrile neutropenia rate reported of 24% by Weycker et al, and Neulasta is appropriate per guidelines.