Severe Chemotherapy-induced Neutropenia Research Articles

Chemotherapy-Induced Neutropenia as a Prognostic Factor in Patients With Advanced Epithelial Ovarian Carcinoma.

To evaluate the prognostic value of chemotherapy-induced neutropenia (CIN) in epithelial ovarian carcinoma (EOC) treated with primary surgery followed by platinum-based chemotherapy. The records of primary EOC treated between Jan 1st 2002 and Dec 31st 2016 were reviewed according to the including and excluding criteria. CIN was defined as absolute neutrophil count (ANC) after chemotherapy <2.0 × 109/L. Patients with CIN were further divided into mild and severe CIN (ANC <1.0 × 109/L), early-onset and late-onset (>3 cycles) CIN. Clinical characteristic was compared by chi-square test. Overall survival (OS) and progression-free survival (PFS) were compared using Kaplan-Meier analysis, univariate and multivariate Cox regression models. Among 735 EOC patients enrolled, no significant differences of the prognosis were found between patients with and without CIN, early and late CIN, mild and severe CIN. However, Kaplan-Meier curve (65 vs 42months for CIN vs non-CIN, P = .007) and Cox regression analysis (HR 1.499, 95% CI 1.142-1.966; P = .004) both revealed that CIN was significantly related with better OS in advanced EOC patients, but not for PFS. So, subgroup analysis was further conducted and date suggested that CIN was an independent predictor of better survival in advanced EOC with suboptimal surgery (PFS: 18 vs 14months, P = .013, HR 1.526, 95% CI 1.072-2.171, P = .019; OS: 37 vs 27 months, P = .013, HR 1.455, 95% CI 1.004-2.108; P = .048). CIN might be used as an independent prognostic indicator of advanced EOC, especially for those patients with suboptimal surgery.

Chemotherapy-induced neutropenia as a prognostic factor in patients with extensive-stage small cell lung cancer.

Chemotherapy-induced neutropenia (CIN) is a dose-limiting factor for cytotoxic chemotherapy, but recently, it was suggested that CIN contributes to prolonged survival. In this study, we examined the association between severe CIN and survival and determined whether CIN affected survival in patients with extensive-stage small cell lung cancer (ES-SCLC). The medical records from 214 patients with ES-SCLC treated with etoposide or irinotecan in combination with cisplatin (EP/IP) between 2012 and 2016 were collected and retrospectively analyzed. Landmark analysis was performed at the end of cycle 4, and the relationship between severe CIN and survival was determined by a log-rank test. In addition, a multivariate analysis using the COX proportional hazard model was performed to identify independent predictive factors. The Landmark analysis included 102 patients in the IP group and 47 patients in the EP group. No significant difference was found between grades 0-3 and grade 4 neutropenia and overall survival (OS) in the EP group (P = 0.57). Contrariwise, for the IP patients, the median OS was 444days for grades 0-3 and 633days for grade 4 neutropenia, which was significantly longer for patients who developed grade 4 neutropenia (P = 0.03). Multivariate analysis adjusted for potential factors revealed that the development of grade 4 CIN was identified as a significant predictor of longer OS (hazard ratio [HR], 0.50; 95% confidence interval (CI), 0.28-0.87, P = 0.015). The results indicated that the development of severe CIN with IP therapy is associated with prolonged OS.

EP08.04-006 Risk Factors of Chemotherapy-Induced Severe Neutropenia in Elderly Lung Cancer: Data From a Regional Hospital in Thailand

Advance stage Non-Small Cell Lung Cancer (NSCLC) is a leading cause of cancer death in the elderly. Chemotherapy is a backbone treatment in non-targetable advance stage NSCLC, especially in limited-resource countries. Chemotherapy—although an effective treatment for NSCLC—has multiple side effects including severe neutropenia. It requires dose reduction, delay in treatment, or discontinuation and induces neutropenic complications resulting in poor oncologic outcomes and increased healthcare costs.

Risk Factors Predicting Chemotherapy-induced Severe Neutropenia and Outcome in Advanced Stage Non-small Cell Lung Cancer: Data from the Limited Resource in Thailand

Introduction: Chemotherapy-induced severe neutropenia requires dose reduction, delay in treatment, or discontinuation, and induces neutropenic complications resulting in poor outcomes and increased healthcare costs. This study aims to identify the risk factors for chemotherapy-induced severe neutropenia and outcome in advanced-stage NSCLC. Method: From July 2014-January 2019, advanced-stage NSCLC who received chemotherapy were retrospectively analyzed. Demographic and risk factors data were collected from the electronic medical record system. Univariate and multivariate logistic regression analyses were performed to identify risk factors for severe neutropenia. Survival curves were estimated using the Kaplan–Meier method. Results: Among 259 patients, 37 (14.28%) and 3 patients (1.2%) developed severe neutropenia and febrile neutropenia respectively. In multivariate analysis, restriction of protein diet (OR 9.54; 95%CI 2.44-37.24; P=0.001), concomitant use herbal medicine (OR 8.66; 95% CI 1.04-72.07; P=0.045), high BMI (OR3.1; 95% CI 1.07-8.99; P=0.04), renal disease (OR 3.9; 95% CI 1.7-8.91; P=0.001), number of cycle chemotherapy &gt; 4 (OR 3.97; 95% CI 1.11-14.18; P=0.03) were significant predictors of Chemotherapy-induced severe neutropenia. No difference in response rate, progression-free survival and overall survival among groups (RR 18.9% vs 26.7%; median PFS; 9.6 vs 8.2 months, P=0.32 and median OS 13.8 vs 16.7 months, P=0.79 in severe and non-severe neutropenia respectively).Conclusions: The present study indicates that protein-restricted diet, concomitant use of herbal medicine, BMI ≥ 25 kg/m2, renal disease, and more than 4 cycles of chemotherapy are significant risk factors for chemotherapy-induced severe neutropenia. Therefore, patients with these risk factors should be more carefully monitored.

Prognostic Implications of Chemotherapy-Induced Neutropenia in Stage III Colorectal Cancer

Previous studies have reported chemotherapy-induced neutropenia (CIN) as a prognostic factor in stage IV colorectal cancer (CRC). However, only few reports analyzed the prognostic value of CIN in patients with stage III CRC who received adjuvant chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX). We aimed to investigate the prognostic implications of CIN in patients with stage III CRC who received adjuvant chemotherapy with FOLFOX. We retrospectively analyzed patients with stage III CRC who received adjuvant chemotherapy with FOLFOX at a tertiary hospital between January 2007 and December 2017. Severe CIN was defined as an absolute neutrophil count of less than 1000/mm3. Three-y disease-free survival (DFS) and overall survival (OS) were analyzed as primary endpoints. Among the 199 patients included in this study, 110 patients (55.3%) experienced severe CIN. There were no significant differences in survival outcomes between the control and CIN groups (control group versus CIN group: 3-y OS, 82.0 % versus 72.7 %; log rank, P=0.250 and 3-y DFS, 71.9 % versus 62.7; log rank, P=0.294). Univariate and multivariate analyses revealed that CIN did not affect DFS and OS in patients with stage III CRC who received adjuvant FOLFOX chemotherapy. Severe CIN occurring during adjuvant FOLFOX chemotherapy did not play a significant role in the prognosis of patients with stage III CRC.

Evaluation of the Association of Polymorphisms With Palbociclib-Induced Neutropenia: Pharmacogenetic Analysis of PALOMA-2/-3.

BackgroundThe most frequently reported treatment‐related adverse event in clinical trials with the cyclin‐dependent kinase 4/6 (CDK4/6) inhibitor palbociclib is neutropenia. Allelic variants in ABCB1 and ERCC1 might be associated with early occurrence (i.e., end of week 2 treatment) of grade 3/4 neutropenia. Pharmacogenetic analyses were performed to uncover associations between single nucleotide polymorphisms (SNPs) in these genes, patient baseline characteristics, and early occurrence of grade 3/4 neutropenia.Materials and Methods ABCB1 (rs1045642, rs1128503) and ERCC1 (rs3212986, rs11615) were analyzed in germline DNA from palbociclib‐treated patients from PALOMA‐2 (n = 584) and PALOMA‐3 (n = 442). SNP, race, and cycle 1 day 15 (C1D15) absolute neutrophil count (ANC) data were available for 652 patients. Univariate and multivariable analyses evaluated associations between SNPs, patient baseline characteristics, and early occurrence of grade 3/4 neutropenia. Analyses were stratified by Asian (n = 122) and non‐Asian (n = 530) ethnicity. Median progression‐free survival (mPFS) was estimated using the Kaplan‐Meier method. The effect of genetic variants on palbociclib pharmacokinetics was analyzed.Results ABCB1 and ERCC1_rs11615 SNP frequencies differed between Asian and non‐Asian patients. Multivariable analysis showed that low baseline ANC was a strong independent risk factor for C1D15 grade 3/4 neutropenia regardless of race (Asians: odds ratio [OR], 6.033, 95% confidence interval [CI], 2.615−13.922, p < .0001; Non‐Asians: OR, 6.884, 95% CI, 4.138−11.451, p < .0001). ABCB1_rs1128503 (C/C vs. T/T: OR, 0.57, 95% CI, 0.311−1.047, p = .070) and ERCC1_rs11615 (A/A vs. G/G: OR, 1.75, 95% CI, 0.901−3.397, p = .098) were potential independent risk factors for C1D15 grade 3/4 neutropenia in non‐Asian patients. Palbociclib mPFS was consistent across genetic variants; exposure was not associated with ABCB1 genotype.ConclusionThis is the first comprehensive assessment of pharmacogenetic data in relationship to exposure to a CDK4/6 inhibitor. Pharmacogenetic testing may inform about potentially increased likelihood of patients developing severe neutropenia (NCT01740427, NCT01942135).Implications for PracticePalbociclib plus endocrine therapy improves hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer outcomes, but is commonly associated with neutropenia. Genetic variants in ABCB1 may influence palbociclib exposure, and in ERCC1 are associated with chemotherapy‐induced severe neutropenia. Here, the associations of single nucleotide polymorphisms in these genes and baseline characteristics with neutropenia were assessed. Low baseline absolute neutrophil count was a strong risk factor (p < .0001) for grade 3/4 neutropenia. There was a trend indicating that ABCB1_rs1128503 and ERCC1_rs11615 were potential risk factors (p < .10) for grade 3/4 neutropenia in non‐Asian patients. Pharmacogenetic testing could inform clinicians about the likelihood of severe neutropenia with palbociclib.

Abstract PS13-34: Differential efficacy of pegfilgrastim (Peg) in patients (pts) with breast cancer (BC) versus other cancer types for the prevention of docetaxel (Doc) chemotherapy-induced neutropenia (CIN)

Abstract Introduction: Peg and other G-CSFs are widely used in BC patients receiving myelosuppressive chemotherapy. We previously reported that Peg’s mechanism of action (MoA) for CIN -prevention protects in week 2 of the cycle. BC pts receiving Doc/Doxorubicin/Cyclophosphamide (TAC) are unprotected in week 1. [Study BPI-2358-106 (NCT03102606) Blayney, St Gallen 2019]. In this study, the novel CIN agent Plinabulin (Plin), with a MoA different, yet complimentary to Peg CIN, prevented severe CIN in week 1 of the Cycle (C), and given in combination with Pegflgrastim, offered superior protection throughout the entire cycle. Other Study 106 results indicated that monotherapy Peg is a sub-optimal CIN prophylaxis strategy in TAC-treated BC pts. In Study BPI-2358-105 (NCT03102606) we evaluated Peg monotherapy as CIN preventive therapy in BC pts. Methods: In Study 105, BC, lung (NSCLC) and prostate cancer (HRPC) pts with at least 1 risk factor as per NCCN guidelines, received Doc 75 mg/m2 with either Peg 6mg (n=53) or Plin 40 mg (n=52), and had frequent blood draws in C1 for Neutrophil count assessment. Grade (Gr) 4 Neutropenia (N) frequency in C1, Duration of Severe Neutropenia (DSN) in C1, and frequency of clinical sequelae of N (Hospitalizations, Infections, FN, antibiotic use, chemotherapy dose reductions) in C1 to C4 were calculated in BC (n=27) and NSCLC/HRPC (n=26) pts receiving Doc 75 mg/m2. There were 9 pts in the HRPC group in the Peg arm. Results:No HRPC and 4% (1pt) NSCLC pts of peg-treated developed Gr 4 N, whereas 16% of Peg-treated BC pts developed Gr 4 N. Gr 4 N frequency over time in C1 was significantly higher in BC pts vs NSCLC/HRPC pts (p&amp;lt;0.016; Cochran-Mantel-Haenszel test; see table below) with Peg. DSN in BC pts was &amp;gt;5 times longer (p&amp;lt;0.005; NBR test) in BC pts vs NSCLC/HRPC pts. DSN was 0.36 Day (D) (95% CI: 0.28; 0.49) in BC pts vs 0.076 Day (95% CI: 0.03; 0.12) in NSCLC/HRPC pts with Peg. Numerically more BC pts vs NSCLC/HRPC pts had clinical sequelae of N with Peg. Conclusions: In BC pts treated with Peg monotherapy after Doc 75 mg/m2, Peg is significantly less effective for CIN prevention compared to NSCLC/HRPC pts. The sub-optimal efficacy of Peg was due to its protection occurring in week 2 of the Cycle, leaving a significant number of pts unprotected in week 1 of the Cycle. The demonstrated effectiveness of Plinabulin in week 1 of the Cycle in BC pts, when combined with Peg could offer superior CIN protection vs Peg alone in BC pts receiving Doc. Gr4N %BaselineC1D1C1D2C1D6*C1D7C1D8C1D9C1D10C1D15BC0%0%0%16%12%4%4%4%0%NSCLC/ HRPC0%0%0%4%4%0%0%0%0%*On C1D6, Gr 4 frequency in the Plin arm was 0% in BC pts Citation Format: Douglas W. Blayney, Greg Ginn, Lan Huang, Ramon Mohanlal. Differential efficacy of pegfilgrastim (Peg) in patients (pts) with breast cancer (BC) versus other cancer types for the prevention of docetaxel (Doc) chemotherapy-induced neutropenia (CIN) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-34.

Contrasting Immunopathogenic and Therapeutic Roles of Granulocyte Colony-Stimulating Factor in Cancer.

Tumor cells are particularly adept at exploiting the immunosuppressive potential of neutrophils as a strategy to achieve uncontrolled proliferation and spread. Recruitment of neutrophils, particularly those of an immature phenotype, known as granulocytic myeloid-derived suppressor cells, is achieved via the production of tumor-derived granulocyte colony-stimulating factor (G-CSF) and neutrophil-selective chemokines. This is not the only mechanism by which G-CSF contributes to tumor-mediated immunosuppression. In this context, the G-CSF receptor is expressed on various cells of the adaptive and innate immune systems and is associated with induction of T cell polarization towards the Th2 and regulatory T cell (Treg) phenotypes. In contrast to the potentially adverse effects of sustained, endogenous production of G-CSF by tumor cells, stringently controlled prophylactic administration of recombinant (r) G-CSF is now a widely practiced strategy in medical oncology to prevent, and in some cases treat, chemotherapy-induced severe neutropenia. Following an overview of the synthesis, structure and function of G-CSF and its receptor, the remainder of this review is focused on: (i) effects of G-CSF on the cells of the adaptive and innate immune systems; (ii) mechanisms by which this cytokine promotes tumor progression and invasion; and (iii) current clinical applications and potential risks of the use of rG-CSF in medical oncology.

Temperatures, diagnostics and treatment in pediatric cancer patients with fever in neutropenia, NCT01683370

In pediatric oncology, there is no evidence-based definition of the temperature limit defining fever (TLDF), which itself is essential for the definition of fever in chemotherapy-induced severe neutropenia (FN). Lowering the TLDF can increase the number of FN episodes diagnosed. This prospective, single center observational study collected data on all temperature measurements, complete blood counts (CBCs), and measures of diagnostics and therapy performed at and after FN diagnosis in pediatric oncology patients using a high standard TLDF (39 °C ear temperature). In 45 FN episodes in 20 patients, 3391 temperature measurements and 318 CBCs, plus information on antibiotics, anti-fungal therapy, antipyretics, blood cultures taken and on discharge were collected. These data can mainly be used to study the influence of virtually lowering the TLDF on diagnostic measures, treatment and length of hospitalization in pediatric FN, which in turn are directly related to costs of FN therapy, and quality of life. This approach can be expanded to include as well different definitions of neutropenia.

Predicting risk of chemotherapy-induced severe neutropenia: A pooled analysis in individual patients data with advanced lung cancer

ObjectivesNeutropenia is associated with the risk of life-threatening infections, chemotherapy dose reductions and delays that may compromise outcomes. This analysis was conducted to develop a prediction model for chemotherapy-induced severe neutropenia in lung cancer. Materials and MethodsIndividual patient data from existing cooperative group phase II/III trials of stages III/IV non-small cell lung cancer or extensive small-cell lung cancer were included. The data were split into training and testing sets. In order to enhance the prediction accuracy and the reliability of the prediction model, lasso method was used for both variable selection and regularization on the training set. The selected variables was fit to a logistic model to obtain regression coefficients. The performance of the final prediction model was evaluated by the area under the ROC curve in both training and testing sets. ResultsThe dataset was randomly separated into training [7606 (67 %) patients] and testing [3746 (33 %) patients] sets. The final model included: age (>65 years), gender (male), weight (kg), BMI, insurance status (yes/unknown), stage (IIIB/IV/ESSCLC), number of metastatic sites (1, 2 or ≥3), individual drugs (gemcitabine, taxanes), number of chemotherapy agents (2 or ≥3), planned use of growth factors, associated radiation therapy, previous therapy (chemotherapy, radiation, surgery), duration of planned treatment, pleural effusion (yes/unknown), performance status (1, ≥2) and presence of symptoms (yes/unknown). ConclusionsWe have developed a relatively simple model with routinely available pre-treatment variables, to predict for neutropenia. This model should be independently validated prospectively.

Neoadjuvant chemotherapy-induced severe neutropenia is associated with histopathological response and survival in locally advanced gastric cancer.

BackgroundNeoadjuvant chemotherapy (NAC) has been shown to improve the prognosis for patients with locally advanced gastric cancer (LAGC). Neutropenia, a predominant chemotherapy-related adverse event, affects the therapeutic course for NAC.MethodsData for 233 patients with LAGC treated with NAC and curative gastrectomy at our center were retrospectively analysed in terms of the relationship between neutropenia and clinicopathological features or outcomes.ResultsNAC-induced neutropenia, NAC-induced severe (grade 3/4) neutropenia (NISN), and a favorable histopathological response (HPR) were observed in 102 (43.8%), 35 (15.0%), and 103 (44.2%) patients, respectively. Together with tumor differentiation, clinical response, and lymphovascular invasion (LVI), and NISN independently predicted a favorable HPR [odds ratio (OR) =4.158, 95% confidence interval (CI): 1.762–9.812, P=0.001). Among patients treated with postoperative chemotherapy, NISN independently predicted poor compliance with postoperative chemotherapy (OR 0.364, 95% CI: 0.148–0.894, P=0.028) and thus poor overall survival (OS) and disease-free survival (DFS). Among patients treated with preoperative chemotherapy alone, NISN was associated with a tendency towards a better DFS (P=0.116) and independently predicted superior OS (hazard ratio =0.253, 95% CI: 0.077–0.830, P=0.023).ConclusionsIn conclusion, our study revealed a link between NISN, HPR, treatment compliance, and survival. NISN is useful for guiding treatment strategies and predicting prognosis for LAGC patients.

Predictive value of monocytes and lymphocytes for short-term neutrophil changes in chemotherapy-induced severe neutropenia in solid tumors.

To explore whether monocytes, lymphocytes, and platelets have a predictive value for short-term neutrophil changes in patients with severe neutropenia (SN) induced by chemotherapy. Complete blood counts (CBC) were collected from a total of 62 patients with chemotherapy-induced SN from December 2013 to March 2018. CBCs at intervals of 1day, 2days, 3days, 4days, and 5days were recorded, and logistic regression analyses were performed to determine whether the monocyte percentage (MP), absolute monocyte count (AMC), lymphocyte percentage (LP), absolute lymphocyte count (ALC), or platelet count (PC) were correlated with short-term neutrophil changes. The areas under the receiver operating characteristic (ROC) curves (AUCs) were calculated for parameters with a P value < 0.05. The MP was significantly correlated with changes in neutrophils for intervals of 1 to 5days, while the LP was significantly correlated with changes in neutrophils for intervals of 2 to 5days. A cutoff value of 6.5% for the MP yielded a sensitivity of 80%, a specificity of 88.6%, and an AUC of 0.908 for predicting an increase in neutrophils on the third day. A cutoff value of 14.75% for the LP yielded a sensitivity of 93.3%, a specificity of 70.3%, and an AUC of 0.812 for predicting an increase in neutrophils on the sixth day. In chemotherapy-induced neutropenia patients, the MP is the best predictor of short-term neutrophil changes. Close monitoring and proper interpretation of the MP and LP are informative in managing chemotherapy-induced neutropenia.

Effects of Chemotherapy-Induced Neutropenia on Overall Survival in Patients With Unresectable or Metastatic Urothelial Carcinoma to Gemcitabine Plus Cisplatin Combination Chemotherapy.

Chemotherapy-induced neutropenia (CIN) is an important dose-limiting toxicity of chemotherapy. However, evidence suggests that the occurrence of CIN may be predictive of treatment outcome. Indeed, studies have revealed that the onset of CIN is associated with a good chemotherapeutic response. The purpose of this study was to investigate the association between the onset of CIN and overall survival in patients with unresectable or metastatic urothelial carcinoma (UC) who received a combination regimen of gemcitabine and cisplatin (GC). Medical records from 56 patients with unresectable or metastatic UC who were treated with a combination GC regimen between December 2005 and May 2016 were retrospectively analyzed to investigate the association between CIN development and survival. The median duration of survival was 521 days (95% CI = 147-193 days) for patients with severe CIN and 287 days for patients without CIN. Additional multivariate analysis revealed that both the presence of severe CIN (hazard ratio [HR] = 0.399; 95% CI = 0.180-0.880, P = 0.023) and baseline hemoglobin (HR = 2.167; 95% CI = 1.170-4.014, P = 0.014) represented independent prognostic factors for the survival of patients with unresectable or metastatic UC receiving GC treatment. Conclusion and Relevance: CIN onset was associated with longer survival in patients receiving GC therapy for unresectable or metastatic UC, suggesting that neutropenia monitoring during GC chemotherapy may be predictive of treatment efficacy.

Chemotherapy-induced neutropenia as a prognostic factor in patients with unresectable pancreatic cancer treated with gemcitabine and nab-paclitaxel.

324 Background: Chemotherapy-induced neutropenia (CIN) has been reported to be associated with a longer survival in patients with various cancers. The aim of our study was to assess whether CIN could also be a prognostic factor in patients with unresectable pancreatic cancer receiving treatment with gemcitabine (GEM) and nab-paclitaxel (nab-PTX). Methods: We retrospectively analyzed the medical records of pancreatic cancer patients who had been treated with GEM and nab-PTX as first-line chemotherapy. CIN was categorized on the basis of the worst WHO grade during chemotherapy: absent/mild (≦ grade 2), or severe (≧ grade 3). The background characteristics and CIN as time-varying covariates (TVCs) were analyzed as potential prognostic factors using a Cox proportional hazards model. Results: We analyzed a total of 291 patients (absent/mild CIN: 116 patients; severe CIN: 174 patients). The median time to severe CIN was 14 days (interquartile range: 10–39 days). The median overall survival (OS) was significantly longer in the severe CIN group than in the absent/mild CIN group (19.2 vs. 11.3 months; p &lt; 0.001) After adjustments, severe CIN was identified as an independent predictor of the OS (HR, 0.54; 95% CI, 0.38–0.77; p = 0.001). In the TVC model also, severe CIN was identified as an independent factor (HR, 0.79; 95% CI, 0.68–0.92; p = 0.002). Conclusions: Severe CIN was associated with a longer survival in patients with pancreatic cancer treated with GEM and nab-PTX.

Prophylaxis of chemotherapy-induced neutropenia and febrile neutropenia with lipegfilgrastim in 2489 cancer patients: final results from the non-interventional study NADIR

Objectives: The non-interventional study (NIS) NADIR (DRKS00005711) evaluated the effectiveness and safety of prophylaxis with lipegfilgrastim, a glycopegylated granulocyte-colony stimulating factor, in 2500 patients undergoing chemotherapy in routine clinical practice. Primary objective was the incidence of chemotherapy-induced severe neutropenia, febrile neutropenia (FN), and neutropenia-associated complications. Methods: NADIR was a prospective NIS conducted in 201 study centers in Germany. Results: The analysis included 2489 patients. Main tumor types were breast cancer (n = 1198, 48.1%), lung cancer (n = 303, 12.2%), non-Hodgkin lymphoma (NHL; n = 337, 13.5%), and prostate cancer (n = 111, 4.5%). Nine hundred and ten (36.6%) patients were aged ≥65 years (regarded as “elderly” patients). Severe neutropenia (CTCAE grade 3/4) was reported in 26.8% (n = 666) and 25.2% (n = 229) of the total population and elderly patients, respectively. FN was documented in 2.7% (n = 68) of the total population vs 3.0% (n = 27) of elderly patients. Primary prophylaxis with lipegfilgrastim among patients with high risk of FN (>20%) was documented in 83.5% of the total population and 75.1% of elderly patients. Infections (CTCAE grade 3/4) were documented in 99 patients (4.0%) in the total population vs 47 (5.1%) elderly patients. Fatal infections were reported in 14 (0.6%) patients in the total population vs 11 (1.2%) elderly patients. Overall, most frequent lipegfilgrastim-related adverse events (AEs) included bone pain (8.0%), anemia (3.2%), leucocytosis (2.7%), and thrombocytopenia (2.5%). Of the patients, 18.0% had ≥1 documented serious AE; none of the fatal events (2.7%) was lipegfilgrastim-related. Conclusions: Lipegfilgrastim administered to patients with solid tumor/NHL undergoing chemotherapy in routine clinical practice showed similar effectiveness and safety compared to the pivotal trials.Trial registration: German Clinical Trials Register identifier: DRKS00005711.

P2.01-35 Predicting Risk of Chemotherapy-Induced Severe Neutropenia in Patients with Advanced Lung Cancer

P2.01-35 Predicting Risk of Chemotherapy-Induced Severe Neutropenia in Patients with Advanced Lung Cancer

Chemotherapy-induced neutropenia risk models to guide the use of myeloid stimulating factors in intermediate risk chemotherapy: A cost and practicality analysis.

10086 Background: The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) have published guidelines for use of prophylactic colony stimulating factors (CSF) for patients at risk for chemotherapy induced neutropenia (CIN). Both recommend CSF if the chemotherapy regimen has a &gt;20% febrile neutropenia (FN) risk. If the regimen is of intermediate CIN risk, the guidelines are less definitive. In this study, we looked at lung cancer patients receiving intermediate CIN risk chemotherapy and applied two risk models developed by Hosmer et al and Bozcuk et al to see if they have adjunct value to the NCCN and ASCO guidelines to more accurately predict CIN. Methods: This was a retrospective study of 43 patients with a diagnosis of lung cancer who were treated with chemotherapy at Drexel University from 2005-2016. Risk models developed by Hosmer et al and Bozcuk et al along with the NCCN and ASCO guidelines were applied to the cohort of patients. Results: The Hosmer calculator recommended giving CSF to 26 patients, the Bozuk calculator for 22 patients, the NCCN guidelines for 25 patients and the ASCO guidelines for 38 patients. Sensitivities, specificities, and pricing information for one course of filgrastim are listed for each risk model in the Table. Conclusions: In lung cancer patients receiving intermediate CIN risk chemotherapy, the Hosmer calculator had the best combination of sensitivity, specificity, and ease of use. The Bozcuk calculator, while accurate, was more difficult to use. The NCCN guidelines missed more patients with severe CIN while the ASCO guidelines gave CSF to the greatest number of patients. The cost for using CSF would have been highest using the ASCO guidelines. Therefore, we recommend the Hosmer calculator for lung cancer patients receiving intermediate risk CIN chemotherapy as it lends to accurate but judicious use of CSF. [Table: see text]

Quantification of EC-18, a synthetic monoacetyldiglyceride (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol), in rat and mouse plasma by liquid-chromatography/tandem mass spectrometry

EC-18 (i.e., 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol), an active ingredient in Rockpid®, has been reported to be useful in controlling various types of inflammations, particularly those caused by neutropenia. Although this product was originally approved as a functional food in Korea, it is currently in phase II clinical trials for use in managing the severe chemotherapy-induced neutropenia in patients with advanced breast cancer who are receiving intermediate febrile neutropenia risk chemotherapy. The objective of this study was to develop a rapid, sensitive method for the determination of EC-18 in rat and mouse plasma and to evaluate the applicability of the assay in pharmacokinetic studies. EC-18 was extracted with MeOH from rat and mouse plasma samples, and the extract directly introduced onto an LC–MS/MS system. The analyte and EC-18-d3, an internal standard, were analyzed by multiple reaction monitoring (MRM) at m/z transitions of 635.4→355.4 for EC-18 and 638.4→338.4 for the internal standard, respectively. The lower limit of quantification (LLOQ) was determined at 50ng/mL, with an acceptable linearity in the range from 50 to 10,000ng/mL (r>0.999) for both matrices. Validation parameters such as accuracy, precision, dilution, recovery, matrix effects and stability were found to be within the acceptance criteria of the assay validation guidelines, indicating that the assay is applicable for estimating EC-18 in concentrations in the range examined. EC-18 was readily determined in plasma samples for periods of up to 8h following an intravenous bolus injection of 1mg/kg in rats and at 5mg/kg in mice, respectively, and up to 24h following the oral administration of 2000mg/kg in mice. The findings indicate that the current analytical method is applicable for pharmacokinetic studies of EC-18 in small animals.

P2.03a-055 Predicting Risk of Chemotherapy-Induced Severe Neutropenia in Lung Patients: A Pooled Analysis of US Cooperative Group Trials: Topic: Clinical Trials

P2.03a-055 Predicting Risk of Chemotherapy-Induced Severe Neutropenia in Lung Patients: A Pooled Analysis of US Cooperative Group Trials: Topic: Clinical Trials

Drug-related genetic polymorphisms affecting severe chemotherapy-induced neutropenia in breast cancer patients: A hospital-based observational study.

Chemotherapy-induced neutropenia (CIN) is one of the major adverse events that necessitate chemotherapy dose reduction. This study aimed to evaluate the association between grade 4 neutropenia and genetic polymorphisms in breast cancer patients. In this genetic polymorphism association study, peripheral blood samples from 100 consecutive breast cancer outpatients, between August 2012 and September 2014, treated with doxorubicin and cyclophosphamide (AC) combination chemotherapy were genotyped for polymorphisms in adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1), cytochrome P450 (CYP) enzyme-coding genes (CYP2B6 and CYP3A5), glutathione S-transferase (GST), and excision repair cross-complementing 1 (ERCC1). Associations between grade 4 neutropenia and genotypes as well as risk factors were examined using multivariate logistic regression. From 100 patients, 32.0% had grade 4 neutropenia. Multivariate logistic regression analysis revealed that ERCC1 118C > T (odds ratio [OR], 3.43; 95% confidence interval [CI], 1.22-9.69; P = 0.020), CYP2B6*6 (OR, 4.51; 95% CI, 1.21-16.95; P = 0.025), body mass index (BMI) (OR, 6.94; 95% CI, 1.15-41.67; P = 0.035), and baseline white blood cell (WBC) count (OR, 2.99; 95% CI, 1.06-8.40; P = 0.038) were significant predictors of grade 4 neutropenia. ERCC1 and CYP2B6 gene polymorphisms were associated with the extent of grade 4 neutropenia in patients receiving AC chemotherapy. In addition to previously known risk factors, BMI and WBC counts, ERCC1 and CYP2B6 gene polymorphisms were also identified as independent strong predictors of grade 4 neutropenia.