Risk Of Neutropenia In Patients Research Articles

Evaluation of neutropenia secondary to mycophenolate mofetil associated with valganciclovir in liver transplant patients

ObjectiveImmunosuppressive drugs are necessary to avoid or reduce the risk of rejection of transplanted organs. The immunosuppression generated may result in these patients needing antibiotics and antivirals to be prescribed to them in conjunction with their immunosuppressants to avoid the risk of infection. This has generated an increase in neutropenia in patients treated with mycophenolate mofetil in combination with valganciclovir. The purpose of this study is to estimate the risk of neutropenia attributable to combination treatment of mycophenolate mofetil with valganciclovir in patients with a transplanted liver. MethodThis is a retrospective cohort study. It included patients who received a liver transplant between 2012 and 2017 and who were treated with mycophenolate mofetil or with a combination of mycophenolate mofetil and valganciclovir. Minimum follow-up was 100 days post-transplantation. Children under 16 years of age and patients who died during follow-up were excluded. Binary logistic regression analysis was used to determine the association of neutropenia with sex, age, diabetes, creatinine at baseline and at discharge, and concomitant treatment of mycophenolate mofetil with valganciclovir. Relative risk and 95% CI were calculated using logistic regression coefficients. Results144 patients were analyzed, 87 were treated with mycophenolate mofetil and 57 received mycophenolate mofetil and valganciclovir together. An overall risk of neutropenia of 37% [95% CI (29-45)] was observed. The risk was significantly higher in patients who received the combination of mycophenolate mofetil and valganciclovir (56%) than in those treated with mycophenolate mofetil alone (24%), p = 0.001. Binary-logistic-regression analysis revealed that concomitant use of mycophenolate mofetil with valganciclovir was associated with an increased risk of neutropenia: Relative risk = 4.97, 95% CI [2.25-11.00]. ConclusionsOur study shows that concomitant use of mycophenolate mofetil and valganciclovir increases the risk of neutropenia in patients with a transplanted liver.

A study indicates an essential link between a mild deterioration in excretory kidney function and the risk of neutropenia during cancer chemotherapy

PurposeNeutropenia, defined as a number of neutrophils in patients’ blood specimen lower than 1500 cells/μm3, is a common adverse event during myelosuppressive oncological chemotherapy, predisposing to febrile neutropenia (FN). Patients with coexisting moderate-to-severe chronic kidney disease (CKD) have an increased risk of FN, included in the guidelines for the primary prophylaxis of FN. However, this does not include mild kidney function impairment with estimated glomerular filtration rate (eGFR) 60–89 ml/min/1.73 m2. This prospective study analyzed the risk of neutropenia in patients on chemotherapy without indication for the primary prophylaxis of FN.MethodsThe study enrolled 38 patients starting chemotherapy, including 26 (68.4%) patients aged 65 years or more. The median duration of follow-up was 76 days. The methodology of creatinine assessment enabled the use of the recommended CKD-EPI formula for identifying patients with a mild reduction of glomerular filtration.ResultsSixteen (42.1%) patients developed at least G2 neutropenia without episodes of FN. Only five (13.1%) patients had eGFR < 60 ml/min/1.73 m2, while 15 (62.5%) eGFR < 90 ml/min/1.73 m2. The relative risk of neutropenia in patients with impaired eGFR was over six times higher than in patients with eGFR > 90 ml/min/1.73 m2 (RR = 6.08; 95%CI:1.45–27.29; p < 0.01).ConclusionsOur observation indicates that even a mild reduction in eGFR is a risk factor for the development of neutropenia and a potential risk factor for FN.

Hematologic toxicities of sunitinib in patients with gastrointestinal stromal tumors: a systematic review and meta-analysis.

Sunitinib offers a significant survival benefit to patients with imatinib-resistant gastrointestinal stromal tumors (GIST). However, the incidence and risk of sunitinib-induced hematologic toxicities in such a population are often overlooked and have not been well characterized. This meta-analysis was performed to assess the summary incidence and risk of hematologic toxicities secondary to sunitinib in patients with GIST. Searches were performed in PubMed, Embase, Cochrane Library, and Web of Science as well as ClinicalTrials.gov to identify relevant studies up to April 2022. Studies with adequate safety profile, including anemia, neutropenia, and thrombocytopenia, were included to calculate the pooled incidence, relative risk (RR), and corresponding 95% confidence intervals (CIs). This study was registered with PROSPERO under number CRD42022328202. A total of 2593 patients from 13 studies were included in the present meta-analysis. For patients with GIST assigned to sunitinib, the overall incidences of all-grade anemia, neutropenia, and thrombocytopenia were 26.2% (95% CI, 14.9-39.4%), 41.8% (95% CI, 29.0-55.1%), and 36.4% (95% CI, 22.8-51.1%), respectively. Regarding high-grade (grades 3 and 4) events, there were 4.7% (95% CI, 3.8-5.6%) for anemia, 9.3% (95% CI, 5.6-13.7%) for neutropenia and 5.0% (95% CI, 2.9-7.3%) for thrombocytopenia. Compared to placebo arms, sunitinib was related to an increased risk of high-grade neutropenia with an RR of 10.39 (95% CI, 1.53-70.72; p = 0.017). Sunitinib carries a relatively high incidence of hematologic toxicities and a substantial increased risk of high-grade neutropenia in patients with GIST. Appropriate prevention and management seem to be inevitable.

667 PEGYLATED RECOMBINANT HUMAN GRANULOCYTE COLONY STIMULATING FACTOR IN DEFINITIVE CHEMORADIOTHERAPY OF ESOPHAGEAL CANCER: PRELIMINARY RESULTS

Abstract To compare the efficiency and safety of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), on the risk of neutropenia in patients with esophageal squamous cell carcinoma (ESCC) of definitive chemoradiotherapy (dCRT). Methods ESCC patients receiving dCRT in our hospital were adopted in this study. Patients in the PEG-rhG-CSF group were treated with preventive PEG-rhG-CSF 6 mg subcutaneously at 24–48 h after completion of chemotherapy of each cycle, while the control group was not. The usage of rhG-CSF was permitted when the absolute neutrophil count (ANC) ≤2 × 109/L, or white blood cell count (WBC) ≤3 × 109/L. Results A total of 34 ESCC patients were in the PEG-rhG-CSF group and 41 were in the control group. Improved chemotherapy cycle completion and radiation dose completion were identified in the PEG-rhG-CSF group (P &amp;lt; 0.001). Leukocyte recovery and neutrophil recovery, (P &amp;lt; 0.001). PEG-rhG-CSF reduced incidence of neutropenia, and time to ANC recovery in different chemotherapy cycles, with (Cycle 1–2, P &amp;lt; 0.001 ~ P = 0.02) or without RT (Cycle 3–4, P = 0.04 ~ P = 0.8799). Antibiotics utilization rates were significantly higher in the PEG-rhG-CSF group during concurrent chemotherapy with RT, but not during consolidative CRT (Cycle 3 and Cycle 4: P &amp;gt; 0.05). Conclusion PEG-rhG-CSF prescribed as prophylaxis reduces acute toxicities by concurrent CRT and contributes to completion of dCRT regime in locally advanced ESCC therapeutics. The significance was not observed in chemotherapy alone without RT in the current findings.

Correlation Between Body Weight and Mitoxantrone-Associated Neutropenia in Dogs.

Thirty-seven dogs with histologically or cytologically confirmed malignant tumors treated with single-agent mitoxantrone at 5 mg/m2 were evaluated in a retrospective study assessing the correlation between body weight and neutropenia associated with a single dose of mitoxantrone in dogs. Overall, eight dogs (21%) experienced grade 3 neutropenia and five dogs (14%) experienced grade 4 neutropenia on day 7 following mitoxantrone chemotherapy. Dogs ≤10 kg body weight were significantly more likely to develop grade 3 or 4 neutropenia (5.8 relative risk; 95% confidence interval, 2.6-12.9; P < .0001) than dogs >10 kg. Dogs ≤15 kg body weight were significantly more likely to develop grade 3 or 4 neutropenia (8.1 relative risk; 95% confidence interval, 2.1-31.3; P < .0001) than dogs >15 kg. Of the 13 patients who developed grade 3 or 4 neutropenia, 6 (46%) were hospitalized for clinical signs related to neutropenia. Based on the severity of neutropenia and the resulting hospitalization seen in dogs ≤10 kg, a dose reduction could be considered for the initial dose of mitoxantrone, and clinicians should be aware of the increased risk of neutropenia in patients 10.1 to ≤15 kg.

Doses dans les organes à risque en radiothérapie conformationnelle et en radiothérapie en conditions stéréotaxiques : os et moelle osseuse

In patients undergoing external radiation therapy, bone marrow and cortical bone structures are all often neglected as organs at risk. Still, from increased febrile neutropenia risk in patients undergoing chemoradiation for a pelvic tumour to increased risk of vertebral fracture when undergoing hypofractioned stereotactic radiotherapy of a spinal metastasis, adverse effects are frequent and sometimes serious. This literature review first defines the rules for contouring these structures, then the dose constraints currently recommended. This article focuses first on conventional irradiation or intensity modulation radiotherapy considering classical fractionation. Secondly, it focuses on stereotactic radiotherapy. The considered organs will be haematopoietic structures, and bone cortical structures. Current recommendations are summarised in a table.

Incidence and risk of neutropenia with palbociclib in patients with cancer: A systematic review and meta-analysis.

e12530 Background: Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6 and has improved the progression-free survival of estrogen receptor positive, metastatic breast cancer (MBC). Its application in other cancers is also undergoing clinical evaluation. Neutropenia, especially high grade (grade 3 or 4), is one of the major side-effects of palbociclib, and the incidence was reported too vary in different studies. In order to better understand the overall risk of palbociclib associated neutropenia, we conducted a systematic review and meta-analysis. Methods: We conducted a systematic literature search (including Medline, Web of Science to November, 2016 and abstracts presented at the ASCO annual meetings from 2009 to 2016). Eligible studies include prospective clinical trials of patients with cancer treated with palbociclib on a 125mg daily 3/4 week schedule and have available data on neutropenia. The incidence and relative risk (RR) of neutropenia were calculated using a random-effects or fixed-effects model, depending on the heterogeneity of the included studies. Results: Eight studies published between 2012 and 2016 included a total of 1515 patients with cancer were eligible for analysis. For patients treated with palbociclib, the overall incidence of all-grade and high grade neutropenia were 77.4% (95% CI 70.9-82.8%) and 60.9% (57.8–63.8%), respectively. Surprisingly, the incidence of neutropenia was significantly different between MBC patients and non-MBC patients (all grade: RR 1.26 [95% CI 1.01–1.56], p = 0.041; high-grade: RR 1.57 [1.23–2.00], p = 0.000) who received palbociclib. Palbociclib was associated with a significantly increased risk of all-grade neutropenia in patients with cancer with an RR of 15.03 (10.17–22.21, p &lt; 0.001) compared with controls. Conclusions: Patients with cancer who received palbociclib have a significant risk of developing neutropenia, especially MBC patients. It is strongly recommended to monitor these patients who are treated with palbociclib to adjust dose, treatment intervals, and avoid infections.

Predicting neutropenia risk in patients with cancer using electronic data.

Clinical guidelines recommending the use of myeloid growth factors are largely based on the prescribed chemotherapy regimen. The guidelines suggest that oncologists consider patient-specific characteristics when prescribing granulocyte-colony stimulating factor (G-CSF) prophylaxis; however, a mechanism to quantify individual patient risk is lacking. Readily available electronic health record (EHR) data can provide patient-specific information needed for individualized neutropenia risk estimation. An evidence-based, individualized neutropenia risk estimation algorithm has been developed. This study evaluated the automated extraction of EHR chemotherapy treatment data and externally validated the neutropenia risk prediction model. A retrospective cohort of adult patients with newly diagnosed breast, colorectal, lung, lymphoid, or ovarian cancer who received the first cycle of a cytotoxic chemotherapy regimen from 2008 to 2013 were recruited from a single cancer clinic. Electronically extracted EHR chemotherapy treatment data were validated by chart review. Neutropenia risk stratification was conducted and risk model performance was assessed using calibration and discrimination. Chemotherapy treatment data electronically extracted from the EHR were verified by chart review. The neutropenia risk prediction tool classified 126 patients (57%) as being low risk for febrile neutropenia, 44 (20%) as intermediate risk, and 51 (23%) as high risk. The model was well calibrated (Hosmer-Lemeshow goodness-of-fit test = 0.24). Discrimination was adequate and slightly less than in the original internal validation (c-statistic 0.75 vs 0.81). Chemotherapy treatment data were electronically extracted from the EHR successfully. The individualized neutropenia risk prediction model performed well in our retrospective external cohort.

Erratum to: UDP-glucuronosyltransferase 1A1*6 and *28 polymorphisms as indicators of initial dose level of irinotecan to reduce risk of neutropenia in patients receiving FOLFIRI for colorectal cancer.

Background Irinotecan (CPT-11)-induced neutropenia is associated with UDP-glucuronosyltransferase (UGT) 1A1*6 and *28 polymorphisms. This prospective study investigated whether using these polymorphisms to adjust the initial dose of CPT-11 as part of FOLFIRI treatment in colorectal cancer patients might improve safety.

UDP-glucuronosyltransferase 1A1*6 and *28 polymorphisms as indicators of initial dose level of irinotecan to reduce risk of neutropenia in patients receiving FOLFIRI for colorectal cancer.

BackgroundIrinotecan (CPT-11)-induced neutropenia is associated with UDP-glucuronosyltransferase (UGT) 1A1*6 and *28 polymorphisms. This prospective study investigated whether using these polymorphisms to adjust the initial dose of CPT-11 as part of FOLFIRI treatment in colorectal cancer patients might improve safety.MethodsAll data were collected by a physician. The relationship between UGT1A1 polymorphisms and first-cycle neutropenia, reasons for treatment discontinuation, and time-to-treatment failure were evaluated. Multivariate analysis was used to assess the risk of neutropenia.ResultsA total of 795 patients were divided into wild-type (*1/*1) (50.1 %), heterozygous (*28/*1, *6/*1) (41.1 %), and homozygous (*28/*28, *6/*6, *28/*6) (8.which are associated with a decrease in the8 %) groups, in which the median starting dose of CPT-11 was 143.0, 143.0, and 115.0 mg/m2, respectively. First-cycle grade ≥3 neutropenia occurred in 17.3, 25.4, and 28.6 % of these patients, respectively. Multivariate analysis revealed that the incidence of grade ≥3 neutropenia was significantly greater in the heterozygous and homozygous groups than in the wild-type group [odds ratio (OR) 1.67; 95 % confidence interval (CI) 1.16–2.42; p = 0.0060, and OR 2.22; 95 % CI 1.22–4.02; p = 0.0088, respectively]. Age (OR 1.77; 95 % CI 1.24–2.53; p = 0.0017), coelomic fluid (OR 1.84; 95 % CI 1.05–3.25; p = 0.0343), and non-reduction in starting dose (OR 1.53; 95 % CI 1.08–2.18; p = 0.0176) were also identified as significant risk factors.ConclusionThe risk of neutropenia was higher in the heterozygous and homozygous groups at initiation of CPT-11 treatment. This suggests that when a reduction in dose is required in patients harboring two variant alleles, the decrease should be approximately 20 %.

Applying a Model to Predict Neutropenia Risk in Patients With Cancer Using Electronic Data

Background/Aims: Granulocyte-colony stimulating factors (G-CSFs) are indicated to decrease the incidence of infections associated with chemotherapy-induced neutropenia (a severe reduction in white blood cells) in cancer patients receiving myelosuppressive chemotherapy. Severe neutropenia or febrile neutropenia occurs in 25–40% of treatment-naïve patients and are associated with increased infection rates, treatment delays, dose reductions, hospitalizations, deaths and increased costs. In addition to the chemotherapy treatment regimen, patient-specific factors influence neutropenic risk. Current guideline recommendations do not include a mechanism to quantify patient risk when determining need to G-CSF support. Studies report over- and underuse of G-CSF among those at low and high risk for neutropenia. A neutropenia risk model developed by Lyman et al. showed prior chemotherapy, relative dose intensity (RDI), abnormal liver and renal function, and low white cell count are major risk factors. We are testing the feasibility of using readily available clinical and administrative data from the HealthPartners electronic medical record and Oncology Treatment Module to apply the Lyman model to data from adult cancer patients receiving first cycle chemotherapy.

History of chronic comorbidity and risk of chemotherapy-induced febrile neutropenia in patients with non-Hodgkin lymphoma not receiving granulocyte colony-stimulating factor prophylaxis

We conducted a cohort study to examine the association between a wide variety of chronic comorbidities and risk of febrile neutropenia (FN) in patients with non-Hodgkin lymphoma (NHL) from 2000 to 2009 treated with chemotherapy at Kaiser Permanente Southern California. History of comorbidities and FN events were identified using electronic medical records. Cox model adjusting for propensity score was used to determine the association between a comorbid condition and FN. Models that additionally adjusted for cancer stage, baseline absolute neutrophil count, chemotherapy regimen and dose reduction were also evaluated. A total of 2480 patients with NHL were included, and 60% received CHOP/R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone, with or without rituximab). In total, 236 (9.5%) patients developed FN in the first chemotherapy cycle. Anemia (adjusted hazard ratio [HR] = 1.6, 95% confidence interval [1.2–2.2]), HIV infection (HR = 3.8 [2.0–6.7]) and rheumatoid diseases (HR = 2.4 [1.3–4.0]) were associated with significantly increased risk of FN. These results provide evidence that chronic comorbidity increases the risk of FN.

Primary vs secondary prophylaxis with pegfilgrastim for the reduction of febrile neutropenia risk in patients receiving chemotherapy for non-Hodgkin’s lymphoma: cost-effectiveness analyses

Objective:Evaluate the cost-effectiveness of primary vs secondary prophylaxis (PP vs SP) with pegfilgrastim to reduce the risk of febrile neutropenia (FN) in Non-Hodgkin’s Lymphoma (NHL) patients receiving myelosuppressive chemotherapy from a US payer perspective.Methods:A Markov model was used to compare PP vs SP with pegfilgrastim in a cohort of patients receiving six cycles of cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) or CHOP plus rituximab (CHOP-R) chemotherapy. Model inputs, including efficacy of pegfilgrastim in reducing risk of FN and costs, were estimated from publicly available sources and peer-reviewed publications. Incremental cost-effectiveness was evaluated in terms of net cost per life-year saved (LYS), per quality-adjusted life-year (QALY) gained, and per FN event avoided over a lifetime horizon. Deterministic and probabilistic analyses were performed to assess sensitivity and robustness of results.Results:Lifetime costs for PP were $5000 greater than for SP; however, PP was associated with fewer FN events and more LYs and QALYs gained vs SP. Incremental cost-effectiveness ratios (ICERs) for PP vs SP for CHOP were $13,400 per FN event avoided, $29,500 per QALY gained, and $25,800 per LYS. CHOP-R results were similar ($15,000 per FN event avoided, $33,000 per QALY gained, and $28,900 per LYS). Results were most sensitive to baseline FN risk, cost per FN episode, and odds ratio for reduced relative dose intensity due to prior FN event. PP was cost-effective vs SP in 85% of simulations at a $50,000 per QALY threshold.Limitations:In the absence of NHL-specific data, estimates for pegfilgrastim efficacy and relative risk reduction of FN were based on available data for neoadjuvant TAC in patients with breast cancer. Baseline risks of FN for CHOP and CHOP-R were assumed to be equivalent.Conclusions:PP with pegfilgrastim is cost-effective compared to SP with pegfilgrastim in NHL patients receiving CHOP or CHOP-R.

Meta-analysis of hematologic toxicities in patients with cancer treated with sunitinib.

373 Background: Sunitinib is a small molecule which inhibits receptor tyrosine kinases involved in cell proliferation and angiogenesis. Though the incidence and risk of unique toxicities associated with sunitinib, such as hypertension and thromboembolic events, have been previously reported, the incidence and risk of hematologic toxicities have been less well characterized. Methods: We searched Medline and the American Society of Clinical Oncology online database of meeting abstracts up to July 2012 for relevant clinical trials. Eligible studies included phase II and III trials and expanded access programs with sunitinib that reported adequate safety data profile reporting neutropenia, thrombocytopenia or anemia. The relative risk (RR), summary incidence and 95% confidence intervals (CI) were calculated. Results: A total of 8,526 patients from 60 trials of sunitinib as a single agent revealed that the incidence of sunitinib-associated all-grade and high-grade (grade 3-4) hematologic toxicities were, respectively: neutropenia: 42.1% and 12.8%; thrombocytopenia: 44.7% and 10.7% and anemia: 50.4% and 6.2%. Sunitinib-treated patients (2,667 subjects from 10 randomized trials) had a significantly increased risk of all-grade (RR = 3.58; 95% CI, 1.71–7.49) and high-grade (RR = 3.32; 95% CI, 1.60–6.90) neutropenia, all-grade (RR = 4.59; 95% CI, 2.76–7.63) and high-grade (RR = 5.84; 95% CI, 2.22–15.41) thrombocytopenia and all-grade anemia (RR = 1.15; 95% CI, 1.00–1.31). Subgroup analysis revealed the significantly higher relative risk of high-grade neutropenia in patients receiving sunitinib monotherapy than in patients receiving concomitant therapy (p = 0.026). There was no statistically significant difference in the incidence of hematologic toxicities between subgroups; renal cell cancer (RCC) versus non-RCC or continuous daily sunitinib dosing versus intermittent dosing. Conclusions: Sunitinib is associated with a significant increase in the risk of developing all-grade and high-grade neutropenia and thrombocytopenia and all-grade anemia compared with control.

738P - Exposure-Response Relationship to Assess the Risk of Neutropenia in Patients with Hepatocellular Carcinoma (HCC) Treated with Tivantinib

Background: Tivantinib is a selective MET inhibitor that is extensively metabolized in the liver. In a randomized, placebo-controlled, phase 2 study in patients with advanced HCC, tivantinib monotherapy improved time to progression by 56%. However, in that study at the standard phase 2 dose of 360 mg twice daily (BID), tivantinib exposure was increased, and the absolute incidence of severe neutropenia increased approximately 6% compared to patients with solid tumors from previous studies. An exposure-response analysis was conducted to explore the relationship between neutropenia and tivantinib pharmacokinetics (PK). Methods: Tivantinib plasma concentration and incidence of grade ≥ 2 neutropenia were pooled from phase 1/1b and 2 studies. A population PK model (NONMEM v.7.1.0) was used to predict tivantinib exposure in HCC. The relationship between tivantinib exposure and neutropenia was evaluated by logistic regression analysis (S-plus v8.0). Results: Data were available from 289 cancer patients, including 73 patients with HCC and mild-to-moderate hepatic impairment. Cases of grade ≥ 3 (n = 28) and grade ≥ 2 (n = 40) neutropenia were included in the analysis. Based on the population PK analysis, tivantinib clearance was reduced approximately 67% in HCC patients, resulting in approximately 3 times higher exposure compared with other cancer patients. There was a significant (P < .001) relationship between tivantinib exposure and incidence of grade ≥ 2/3 neutropenia. By reducing the tivantinib starting dose from 360 to 240 mg BID, the incidence of grade ≥ 3 neutropenia is modeled to decrease from 28% to 16% in HCC patients. Further reduction in the risk of neutropenia (~6%) was achieved with intensive clinical monitoring and an aggressive dose-reduction schema. Conclusions: Based on the current analysis, the increased incidence of neutropenia in HCC patients compared to patients with other solid tumors resulted from increased tivantinib exposure due to hepatic impairment. Consistent with the model, the risk of neutropenia was successfully managed in HCC patients by implementing dose reduction and tighter clinical monitoring without compromising efficacy. • Patients with PK data from 4 studies were used to determine tivantinib exposure (Table 1) • Patients with safety data from 8 studies were used to evaluate the relationship between tivantinib exposure and incidence of neutropenia (Table 2) - A total of 289 patients, including 73 patients with HCC and mild-to-moderate hepatic impairment, were analyzed - There were 28 events of grade ≥ 3 neutropenia • Tivantinib steady state exposure was approximately 3 times higher in patients with HCC than in patients who had other cancers (Figure 1) - Tivantinib clearance was reduced by approximately 67% in patients with HCC • Among patients with mild to moderate hepatic impairment, Child-Pugh score also

Efficacy and safety of half-dose pegfilgrastim in cancer patients receiving cytotoxic chemotherapy.

9110 Background: Pegfilgrastim reduces neutropenia risk in patients (pts) on cytotoxic chemotherapy. A single 6 mg dose per chemotherapy cycle commonly causes bone pain and leukocytosis. While half-dose pegfilgrastim has been shown to be safe and effective in breast cancer pts, there is no data on half-dose pegfilgrastim in general oncology pts. Methods: We evaluated the efficacy and safety of half-dose pegfilgrastim in general oncology pts on cytotoxic chemotherapy at St Francis Cancer Center. Pts who received at least one dose of 6 mg pegfilgrastim and developed NCI-CTCAE grade 2 or more bone pain and/or leukocytosis (WBC&gt;10,000/ml) were given 3 mg dose pegfilgrastim on their following chemotherapy cycles. Pt demographics, type/number of chemotherapy regimens, efficacy, side effects and complications were evaluated. McNemar’s test, logistic regression analysis and ANOVA were used for statistical analysis. Results: Twenty-six pts (3 males, 23 females, all Caucasian) with median age 55 (range 34-86) received a total of eighty-three 3 mg doses of pegfilgrastim. Cancers treated were breast (N=16), colorectal (N=7), head and neck (N=1), non-Hodgkin lymphoma (N=1) and non-small cell lung cancer (N=1). Chemotherapy received was anthracycline (N=9), taxane (N=7), 5-FU/oxaliplatin (N=7), 5-FU/cisplatin (N=1), gemcitabine/oxaliplatin (N=1), pemetrexed/carboplatin (N=1). No neutropenia or chemotherapy dose modifications occurred on half-dose pegfilgrastim. In the 26 pts we report, bone pain occurred in 23 pts at 6 mg and 14 pts at 3 mg dose. Leukocytosis occurred in 23 pts at 6 mg and only 2 pts at 3 mg dose (McNemar’s test, P&lt;0.01). While older age and full-dose pegfilgrastim were predictive of bone pain, more than one line of chemotherapy and half-dose pegfilgrastim were predictive of lack of leukocytosis (logistic regression analysis/ANOVA, P&lt;0.01). Conclusions: Half-dose pegfilgrastim in general oncology pts receiving cytotoxic chemotherapy seems to be safe and effective with less bone pain and leukocytosis without resultant neutropenia or need for chemo modification. Larger prospective studies of half-dose pegfilgrastim in this setting are needed to further understand the feasibility of this approach.

Incidence and Risk of Severe Neutropenia in Advanced Cancer Patients Treated with Cetuximab

Background and Aim: Neutropenia is a serious adverse event for patients who are treated with cetuximab, an inhibitor of endothelial growth factor receptor. However, there is no consistent result of the relationship between cetuximab and neutropenia in randomized controlled trials (RCTs). We did a systematic review and meta-analysis of published RCTs to assess the overall risk of neutropenia associated with cetuximab.Methods: PubMed, Cochrane Central Register of Controlled Trials, EMBASE, and American Society of Clinical Oncology conferences were searched for relevant RCTs. Quantitative and qualitative analyses were carried out to evaluate the association between neutropenia and cetuximab. Both the fixed-effect model and random-effects model were used.Results: A total of 7186 patients with a variety of advanced cancers from 14 trials were included in our analysis. The overall incidence of neutropenia in patients receiving cetuximab was 33% (95% CI 26, 43). Patients treated with cetuximab had a significantly increased risk of neutropenia compared with patients treated with control medication, with a relative risk (RR) of 1.12 (95% CI 1.05, 1.19; fixed-effect model). Risk varied with tumor type. Higher risks were observed in patients with colorectal carcinoma (RR 1.17; 95% CI 1.04, 1.32; fixed-effect model) and non-small cell lung cancer (RR 1.07; 95% CI 0.99, 1.16; fixed-effect model).Conclusion: Cetuximab is associated with a significant risk of neutropenia in patients with advanced cancer receiving concurrent chemotherapy.

Abstract B129: Use of white blood cell growth factors and risk of acute myeloid leukemia or myelodysplastic syndrome among elderly non-Hodgkin's lymphoma patients

Abstract Therapy-related myelodysplastic syndromes and acute myeloid leukemia (t-MDS/AML), defined as MDS or AML occurring after myelosuppressive chemotherapy and/or radiation therapy, are devastating long-term complications of cancer therapy. White blood cell growth factors (CSFs) are supportive care agents intended to minimize risk of febrile neutropenia in patients receiving chemotherapy. However, evidence suggests that CSFs may increase risk of t-MDS/AML, possibly due to the observation that CSFs not only stimulate the proliferation and differentiation of hematopoietic stem cells, but also interfere with apoptosis. The purpose of this study was to evaluate the association between CSF use and t-MDS/AML among a large population-based cohort of elderly non-Hodgkin's lymphoma (NHL) patients treated with chemotherapy. We identified 13,203 NHL patients from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database diagnosed from 1992 to 2002 who received chemotherapy within 12 months of diagnosis. Patients were followed from their initial chemotherapy date until t-MDS/AML development, death, or end of study period (October 31, 2006). Overall, 40% (n=5,266) of patients received CSF. A total of 272 (5.2%) of patients receiving CSF developed t-MDS/AML vs. 230 (2.9%) who did not receive CSF: there was a statistically significant higher incidence of t-MDS/AML among patients receiving CSF compared to patients not receiving CSF (log-rank p&amp;lt;0.0001). In a multivariable Cox regression analysis adjusting for gender, histology, stage, comorbidities, chemotherapy dates, and chemotherapy agent, CSF use was independently associated with a 53% increased risk of t-MDS/AML (HR 1.53; 95% CI 1.26 – 1.84). A dose-response relationship was observed, with t-MDS/AML risk increasing by quartile of CSF claims. In an evaluation of plausible biologic interactions, we found that patients who received both CSF and antimetabolite chemotherapy had a 2.5 fold increased risk of t-MDS/AML (HR 2.49; 95% CI 1.91 – 3.26) vs. patients who received neither agent (p-interaction=0.04). This observation has added clinical significance considering that approximately 10% of the overall population received this therapeutic combination. To our knowledge, this is the first large population-based study to evaluate the association between CSF use and t-MDS/AML risk among NHL patients. Findings support our hypothesis that the administration of CSF among elderly NHL patients receiving chemotherapy may increase the risk of t-MDS/AML, even though the absolute risk is low in these populations. Future studies are necessary to verify these results and to determine the potential clinical implications of the observed interaction between CSF use and antimetabolite chemotherapy. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B129.

Pharmacogenetics and irinotecan therapy

Irinotecan metabolism, irinotecan pharmacogenetic research, and the role of genetic testing before administration of the drug are reviewed. Irinotecan is approved worldwide for the treatment of metastatic colorectal cancer but causes dose-limiting neutropenia and diarrhea. When severe, these can lead to dehydration, infection, patient discomfort, additional medication requirements, hospitalization, and death. The identification of predictive markers in irinotecan therapy has been a significant goal of pharmacogenetic research. The labeling of irinotecan was recently changed and now includes a warning of greater neutropenia risk in patients with reduced activity in the drug-metabolizing enzyme uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). A known marker of reduced UGT1A1 activity is the genetic variant UGT1A1*28. Numerous studies have demonstrated the effects of genetic factors, especially UGT1A1*28, that contribute to interpatient variability in irinotecan pharmacokinetics and toxicity. Irinotecan's new labeling recommends that clinicians consider reducing the dosage of irinotecan in patients homozygous for UGT1A1*28. At least part of the interpatient variability of irinotecan toxicity can be explained by the UGT1A1*28 polymorphism. Patients who are homozygous for the UGT1A1*28 allele have an increased risk of developing severe neutropenia when receiving irinotecan, especially the 300-350- mg/m2 regimen. A molecular assay is now available to identify the at-risk subgroup and should be used by health care professionals to help guide irinotecan-treatment decisions.