Comparing risk models guiding growth factor use in chemotherapy
Background The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) have guidelines for using colony-stimulating factors (CSF) for chemotherapy-induced neutropenia (CIN). Both groups recommend CSF if the chemotherapy has a risk for febrile neutropenia of more than 20%. The guidelines are less definitive if the risk is intermediate (10%-20%). Two risk models developed by Hosmer and Bozcuk and their respective colleagues may provide guidance regarding CSF decision making in this intermediate risk population.
Objective To examine whether risk models developed by Hosmer and Bozcuk had adjunct value to the NCCN and ASCO guidelines when applied to patients with lung cancer who were receiving intermediate-risk chemotherapy.
Methods Male and female patients aged 18-75 years with a diagnosis of any stage lung cancer, small or non-small cell, who required and received their initial chemotherapy at Drexel University in Philadelphia were included in this study. Patients who received growth factor before their chemotherapy were excluded. The Hosmer and Bozcuk calculators for febrile neutropenia risk and the NCCN and ASCO guidelines for using CSF for CIN were applied to this group of patients.
Results 43 patients were included in the study. The Hosmer and Bozcuk calculators and NCCN and ASCO guidelines recommended giving CSF to 26, 22, 25, and 38 patients, respectively. The sensitivities for detecting severe CIN were 89%, 78%, 67%, and 97%, and the specificities were 44%, 56%, 45%, and 14%, respectively.
Limitations Small cohort size; data were limited in scope.
Conclusions In lung cancer patients receiving intermediate-risk chemotherapy, the Hosmer calculator had the best combination of sensitivity, specificity, and ease of use. The NCCN guidelines were less sensitive, whereas the ASCO guidelines were the least specific. Based on these findings, we recommend using the Hosmer calculator because it lends to accurate but judicious use of CSF.
Accepted for publication November 2, 2018
Correspondence Chetan Jeurkar, DO; jeurkar2@gmail.com
Disclosures The authors report no disclosures/conflicts of interest.
©2018 Frontline Medical Communications
doi https://doi.org/10.12788/jcso.0429
Chemotherapy-induced neutropenia (CIN) and its corollary febrile neutropenia (FN) are well recognized, and they are serious consequences of many agents used in the treatment of malignancy. FN in particular has been associated with a considerable risk of morbidity and mortality, namely sepsis with multiorgan failure and eventual death. 1 The mainstay of prophylaxis for patients who are deemed to be at high risk for CIN and FN is colony-stimulating factors (CSF). These agents have been shown to significantly decrease FN-related mortality, and therefore their use is potentially life-saving. 2 However, CSF are not cheap, with the cost of peg-filgrastim as much as US $6195.99 per cycle of chemotherapy. 3 Therefore, not only do FN and CIN pose significant risk to patients, they also carry a high burden of cost to the patient and health care system both in treatment and prophylaxis. 4 As such, it is prudent for oncologists to accurately identify high-risk patients and judiciously use CSF in an evidence-based manner.
However, this has proven to be difficult because of the extent of variability between patients and the heterogeneity of the various risk models in the literature. Currently, there are 2 widely used guidelines, 1 developed by the National Comprehensive Cancer Network (NCCN) and another by the American Society of Clinical Oncology (ASCO). Both guidelines suggest the use of prophylactic CSF if the chemotherapy regimen has an FN risk of more than 20% (high risk). If the chemotherapy is deemed to be of intermediate risk (10%-20% FN risk), then patient-specific factors need to be considered. 5,6
In lung cancer, the NCCN lists only topotecan for small cell carcinomas as being high risk for FN, and therefore it is the only regimen that would warrant definitive use of prophylactic CSF. 5 The most recent ASCO guidelines do not list chemotherapy regimens that are high risk for FN. 6 For intermediate-risk regimens, the NCCN states that CSF prophylaxis should be considered if the patient has had previous chemotherapy or radiation therapy, persistent neutropenia, bone marrow involvement by tumor, recent surgery or open wounds, liver dysfunction (total bilirubin, >2.0 mg/dL), or renal dysfunction (creatinine clearance, <50 mL/min), or is older than 65 years. 5
ASCO guidelines state that in intermediate-risk chemotherapy regimens, the following factors are to be considered: age >65 years, advanced disease, previous chemotherapy or radiation therapy, pre-existing neutropenia or marrow involvement by tumor, infection, open wounds or recent surgery, poor performance status or nutritional status, poor renal function, liver dysfunction (most notably bilirubin elevation), cardiovascular disease, multiple comorbid conditions, and HIV infection. However, in the ASCO guidelines, there is no suggestion as to whether CSF should be administered if patients have one of these risk factors, only to “consider these factors when estimating patients’ overall risk of febrile neutropenia.” 6
There is some uncertainty with the NCCN and ASCO guidelines as to whether prophylactic CSF should be given to these intermediate-risk patients. There are suggestions but no definitive guidelines. In our study, we looked at lung cancer patients treated with intermediate-risk chemotherapy regimens and applied 2 different risk models created by Hosmer 7 and Bozcuk 8 and their respective colleagues (Hosmer and Bozcuk hereinafter). Our goal was to assess the efficacy differences between the 2 risk models and to compare their outcomes and recommendations with the NCCN and ASCO guidelines. This was done to showcase the tools available to a clinical oncologist who must decide whether to prescribe prophylactic CSF in these more challenging clinical situations.
