Risk Models for Predicting Chemotherapy-Induced Neutropenia

Lyman, Gary H.; Lyman, Christopher; Agboola, Olayemi

doi:10.1634/theoncologist.10-6-427

Cited by 290 publications

(236 citation statements)

References 53 publications

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“…[4][5][6] Major risk factors for the development of FN include older age, comorbid conditions, the type of cancer, and the type and number of myelosuppressive chemotherapy agents used. [5][6][7] FN represents a lifethreatening complication that requires urgent evaluation for the identification and treatment of documented or presumed infection. 8 Infection in the neutropenic cancer patient often can be difficult to identify because of the lack of neutrophils and associated clinical symptoms and signs.…”

Section: Fn and Early Mortalitymentioning

confidence: 99%

Risk of mortality in patients with cancer who experience febrile neutropenia

Lyman

Michels²,

Reynolds³

et al. 2010

Cancer

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223

154

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BACKGROUND: Febrile neutropenia (FN) is a serious and potentially life-threatening condition that may develop in patients with cancer who receive myelosuppressive chemotherapy. The risk of mortality from FN is not well characterized in current clinical practice. METHODS: Patients with cancer who were receiving chemotherapy in clinical practice were identified from a large US healthcare claims database, and mortality was confirmed using the National Death Index. Patients with FN had their propensity scores matched within tumor types of interest (non-Hodgkin lymphoma and breast, lung, colorectal, and ovarian cancers) to patients who did not experience FN. Study endpoints of overall mortality (anytime during follow-up), early mortality (during the first 12 months of the first chemotherapy course), and hospitalization were examined using univariate and multivariate techniques. RESULTS: Matched FN and control groups each included 5990 patients, and the average follow-up for both groups was 17.6 months. Crude incidence rates of early mortality were significantly higher for patients with FN compared with controls for all tumor types. Proportional hazards regression demonstrated a significant increase in the risk of overall and early mortality in patients with FN compared with controls (hazard ratio [HR], 1.15 [95% confidence interval, 1.02-1.29] and HR, 1.35 [95% confidence interval, 1.09-1.67], respectively). CONCLUSIONS: The adjusted risk of mortality in patients who experienced FN was at least 15% higher than in comparably matched patients without FN, supporting the inference that infectious complications because of neutropenia resulting from myelosuppressive chemotherapy are clinically important.

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Section: Fn and Early Mortalitymentioning

confidence: 99%

Risk of mortality in patients with cancer who experience febrile neutropenia

Lyman

Michels²,

Reynolds³

et al. 2010

Cancer

Self Cite

223

154

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“…Simulations showed that the impact of the different schedules was negligible. Several authors have suggested that female gender is among others a significant predictor of neutropenia and is considered a risk factor in the Guidelines for the use of Colony-Stimulating factors in Managing Neutropenia [27]. However, gender was not found as a clinically relevant covariate in PK/PD models for neutropenia although a statistical significance was shown [19,28].…”

Section: Absolute Neutrophil Count-time Profile Vpcmentioning

confidence: 99%

Semi-mechanistic population pharmacokinetic/pharmacodynamic model for neutropenia following therapy with the Plk-1 inhibitor BI 2536 and its application in clinical development

Soto

Staab

Tillmann

et al. 2010

Cancer Chemother Pharmacol

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Purpose (1) To describe the neutropenic response of BI 2536 a polo-like kinase 1 inhibitor in patients with cancer using a semi-mechanistic model. (2) To explore by simulations (a) the neutropenic effects for the maximum tolerated dose (MTD) and the dose at which dose-limiting toxicity occurred, (b) the possibility to reduce the cycle duration without increasing neutropenia substantially, and (c) the impact of the initial absolute neutrophil count (ANC) on the degree of neutropenia for different doses. Experimental design BI 2536 was administered as intravenous infusion over 60 min in the dose range from 25 to 250 mg. Three different administration schedules were explored: (a) day 1, (b) days 1, 2, and 3 or (c) days 1 and 8 within a 3 week treatment cycle. BI 2536 plasma concentrations and ANC obtained during the first treatment cycle from 104 patients were analysed using the population approach with NONMEM VI. Results Neutropenia was described by a semi-mechanistic model resembling proliferation at the stem cell compartment, maturation, degradation, and homeostatic regulation. BI 2536 acts decreasing proliferation rate.Simulations showed that (1) all MTD doses showed an acceptable risk of neutropenia, (2) when BI 2536 is given as 200 mg single administration, cycle duration can be reduced from 3 to 2 weeks, and (3) baseline ANC might be considered to individualise the dose of BI 2536. Conclusions A semi-mechanistic population model was applied to describe the neutropenic effects of BI 2536. The model was used for simulations to support further clinical development.

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“…The risk of developing FN is normally associated with the cancer treatment. For example, hematological malignancies are associated with a higher risk of FN compared with solid tumors, due to the process of the disease and its treatment (21,22). When comparing solid tumors, patients with lung cancer appear to exhibit a higher incidence rate of FN (5).…”

Section: Discussionmentioning

confidence: 99%

Epidemiology and characteristics of febrile neutropenia in oncology patients from Spanish tertiary care hospitals: PINNACLE study

Castro

Gascón-Vilaplana

Tejerina

et al. 2015

Molecular and Clinical Oncology

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Abstract. Febrile neutropenia (FN) is one of the most common adverse events associated with myelosuppressive chemotherapy for cancer treatment. The objective of this study was to describe the incidence of hospitalization due to FN in Spanish tertiary care hospitals (PINNACLE study). This epidemiological, retrospective, multicenter, nationwide study involved 119 patients from oncology units of 10 Spanish tertiary care hospitals who were admitted for FN. The primary endpoint was to assess the epidemiology and characteristics of FN. The incidence of admissions due to FN in oncology patients was 2.0% (interquartile range [IQR], 1.6-3.0). In terms of fever and absolute neutrophil count (ANC), 37.0% of the patients had a temperature of ≥38.2˚C and an ANC of ≤500/m 3 . The number of patients who received prophylactic treatment with granulocyte colony-stimulating factor (G-CSF) was significantly higher in the palliative group (32.6%) compared with that in the non-palliative group (13.5%). The hospital length of stay was significantly shorter in patients who received prophylactic G-CSF compared with those who did not (5.0 days; IQR, 4.0-9.0 vs. 7.0 days; IQR, 5.0-11.0, respectively). The hospital length of stay was also significantly shorter in patients receiving palliative treatment (5.0 days; IQR, 3.0-7.0) compared with those receiving non-palliative therapy (7.0 days; IQR, 5.0-12.0). In conclusion, the incidence of admissions due to FN in oncology patients was 2.0% and the duration of hospital stay was 7.0 days. Prophylactic G-CSF treatment was found to be associated with better outcomes and shorter hospital stays. Therefore, the use of this treatment becomes relevant for achieving better clinical outcomes and reducing hospitalization cost in the management of FN.

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Risk Models for Predicting Chemotherapy-Induced Neutropenia

Cited by 290 publications

References 53 publications

Risk of mortality in patients with cancer who experience febrile neutropenia

Risk of mortality in patients with cancer who experience febrile neutropenia

Semi-mechanistic population pharmacokinetic/pharmacodynamic model for neutropenia following therapy with the Plk-1 inhibitor BI 2536 and its application in clinical development

Epidemiology and characteristics of febrile neutropenia in oncology patients from Spanish tertiary care hospitals: PINNACLE study

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