D. C. Dale

Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review

PURPOSE Randomized controlled trials (RCTs) of prophylactic granulocyte colony-stimulating factors (G-CSF) have demonstrated a significant reduction in febrile neutropenia (FN) after systemic chemotherapy. Several RCTs have been published recently that investigate the impact of G-CSF on mortality and relative dose-intensity (RDI). METHODS A comprehensive systematic review and meta-analysis of all reported RCTs comparing primary prophylactic G-CSF with placebo or untreated controls in adult solid tumor and malignant lymphoma patients was undertaken without language restrictions, using electronic databases, conference proceedings, and hand-searching techniques. Two reviewers extracted data independently. Summary estimates of relative risk (RR) with 95% CIs were estimated based on the method of Mantel-Haenszel and DerSimonian and Laird. RESULTS Seventeen RCTs were identified including 3,493 patients. For infection-related mortality, RR reduction with G-CSF compared with controls was 45% (RR = 0.55; 95% CI, 0.33 to 0.90; P = .018); for early mortality (all-cause mortality during chemotherapy period), it was 40% (RR = 0.60; 95% CI, 0.43 to 0.83; P = .002); and for FN, it was 46% (RR = 0.54; 95% CI, 0.43 to 0.67; P < .001). Average RDI was significantly higher in patients who received G-CSF compared with control patients (P < .001). Bone or musculoskeletal pain was reported in 10.4% of controls and 19.6% of G-CSF patients (RR = 4.03; 95% CI, 2.15 to 7.52; P < .001). Significant reductions in FN with G-CSF were observed in studies allowing secondary G-CSF prophylaxis in controls and in the three trials with concurrent prophylactic antibiotics in both treatment arms. CONCLUSION Prophylactic G-CSF reduces the risk of FN and early deaths, including infection-related mortality, while increasing RDI and musculoskeletal pain. There are insufficient data to assess the impact of G-CSF on disease-free and overall survival.

Incidence and Predictors of Low Chemotherapy Dose-Intensity in Aggressive Non-Hodgkin's Lymphoma: A Nationwide Study

PURPOSE To assess the incidence of and risk factors for reduced relative dose-intensity (RDI) in patients treated with chemotherapy for aggressive non-Hodgkins lymphoma (NHL). METHODS A nationwide survey was conducted of 567 oncology practices with data extracted from the records of 4,522 patients with aggressive NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); CHOP-rituximab (CHOP-R); or cyclophosphamide, mitoxantrone, vincristine, and prednisone (CNOP). The primary outcome was the average RDI for each regimen based on both planned and reference standards. Other assessments included the incidence of febrile neutropenia and patterns of colony-stimulating factor (CSF) use, as well as the average RDI in high-risk subgroups. RESULTS Dose reductions > or = 15% occurred in 40% of patients and treatment delays > or = 7 days occurred in 24% of patients, resulting in 53% and 48% of patients receiving an RDI less than 85% of the minimum six-cycle and National Comprehensive Cancer Network guideline standards, respectively. Reduced RDI was more prevalent in older patients, with 60% of patients older than 60 years receiving RDI less than 85%. Multivariate analysis identified several independent predictors for reduced RDI, including age older than 60 years, advanced disease stage, poor performance status, and no prophylactic CSF use. Age was no longer a significant risk factor in patients who received prophylactic CSF. CONCLUSION Patients with aggressive and potentially curable NHL treated with CHOP, CHOP-R, or CNOP frequently receive reduced RDI. Predictive models based on the risk factors identified for reduced RDI should enable the targeted use of appropriate supportive care, facilitating the delivery of full chemotherapy doses on schedule.

Effect of Patient Socioeconomic Status and Body Mass Index on the Quality of Breast Cancer Adjuvant Chemotherapy

PURPOSE The purpose of this study was to investigate the relationship between socioeconomic status (SES) and the use of intentionally reduced doses of chemotherapy in the adjuvant treatment of breast cancer. PATIENTS AND METHODS Patients with breast cancer treated with a standard chemotherapy regimen (n = 764) were enrolled in a prospective registry after signing informed consent. Detailed information was collected on patient, disease, and treatment, including chemotherapy doses. Zip code level data on median household income, proportion of people living below the poverty level, and educational attainment were obtained from the US Census. Doses for the first cycle of chemotherapy lower than 85% of standard were considered to be reduced. Univariate analyses and multivariate logistic regression were performed to identify factors associated with the use of reduced first cycle doses. RESULTS In univariate analysis, individual education attainment, zip code SES measures, body mass index, and geographic region were all significantly associated with receipt of intentionally reduced doses of chemotherapy. In multivariate analysis, controlling for geography, factors independently associated with reduced doses were obesity (odds ratio [OR], 2.47; 95% CI, 1.36 to 4.51), severe obesity (OR, 4.04; 95% CI, 1.46 to 11.19), and education less than high school (OR, 3.07; 95% CI, 1.57 to 5.99). CONCLUSION Social disparities in breast cancer outcomes may be in part the result of lower quality chemotherapy doses in the adjuvant treatment of breast cancer. Efforts to address such prescribing patterns may help reduce SES disparities in breast cancer survival.

Social and Racial Differences in Selection of Breast Cancer Adjuvant Chemotherapy Regimens

PURPOSE Breast cancer outcomes are worse among black women and women of lower socioeconomic status. The purpose of this study was to investigate racial and social differences in selection of breast cancer adjuvant chemotherapy regimens. METHODS Detailed information on patient, disease, and treatment factors was collected prospectively on 957 patients who were receiving breast cancer adjuvant chemotherapy in 101 oncology practices throughout the United States. Adjuvant chemotherapy regimens included in any of several published guidelines were considered standard. Receipt of nonstandard regimens was examined according to clinical and nonclinical factors. Differences between groups were assessed using chi2 tests. Multivariate logistic regression was used to identify factors associated with use of nonstandard regimens. RESULTS Black race (P = .008), lower educational attainment (P = .003), age 70 years (P = .001), higher stage (P < .0001), insurance type (P = .048), employment status (P = .045), employment type (P = .025), and geographic location (P = .021) were associated with the use of nonstandard regimens in univariate analyses. In multivariate analysis, black race (P = .020), lower educational attainment (P = .024), age > or = 70 years (P = .032), and higher stage (P < .0001) were associated with receipt of nonstandard regimens. CONCLUSION The more frequent use of non-guideline-concordant adjuvant chemotherapy regimens in black women and women with lower educational attainment may contribute to less favorable outcomes in these populations. Addressing such differences in care may improve cancer outcomes in vulnerable populations.

Granulocyte transfusion therapy for infections in candidates and recipients of HPC transplantation: a comparative analysis of feasibility and outcome for community donors versus related donors

BACKGROUND: Feasibility, response to granulocyte transfusion therapy, and clinical outcome were compared among HPC transplant recipients enrolled in a prospective study of a community blood bank‐based unrelated donors program, a prospective granulocyte study using family donors, and matched control patients without granulocyte transfusion therapy.

Risk of neutropenic complications based on a prospective nationwide registry of cancer patients initiating systematic chemotherapy

6125 Background: Myelosuppression represents the major dose-limiting toxicity of cancer chemotherapy. A prospective, nationwide study was undertaken to define risk factors for neutropenic complications (NC) and to develop risk models for selecting patients for hematopoietic support. METHODS More than 2,500 patients have been prospectively registered at 137 randomly selected practice sites. Primary outcomes included documented severe neutropenia (SN) (ANC<500), NC ( fever/ infection/other) and severe neutropenic events (SNE) (SN or NC). RESULTS This preliminary analysis is based on the first 2,222 patients treated to date including 886 (40%) age ≥ 65. One-third did not receive at least four cycles of chemotherapy due to disease progression (55%), refusal (11%), death (11%) and unknown (23%). Neutropenia (ANC <1000) was documented in 40% including SN in 26%. More than one-half of all initial events occurred during cycle 1. [Figure: see text] In addition to cancer and regimen type, significant predictors of SN included gender (.001), baseline neutrophils (.01), diabetes (.037) and chronic lung disease (.001). Significant predictors of NC included gender (.004) and stage (.04). In addition to cancer and regimen type, significant predictors of SNE included gender (.006), stage (.007) and COPD (.029). The risk of SNE in all cycles (1st cycle) includes: breast: 49(36); lung 31(20); lymphoma 42(33); ovary 37(17); colon 18(8). CONCLUSIONS NC and SNE occur early in the course of therapy potentially compromising chemotherapy dose intensity and clinical outcomes. Significant independent risk factors include cancer type, regimen, dose intensity, gender, stage and several comorbidities. [Table: see text].

Complications and costs associated with febrile neutropenia in hospitalized adult cancer patients

6049 Background: Fever in the setting of neutropenia (FN) frequently requires hospitalization for empiric broad-spectrum antibiotics. More complete understanding of the medical complications and costs associated with hospitalization for FN is needed. METHODS Hospitalization of cancer patients with FN at 115 academic medical centers between 1995 and 2000 was studied using the discharge database of the University HealthSystem Consortium. Primary outcomes included length of stay (LOS), cost, infectious complications and mortality. Logistic regression analysis was used to estimate relative risk based on adjusted odds ratios (OR). RESULTS Hospitalization with FN was reported in 41,779 adult cancer patients. Mean (median) LOS was 11.2 (6) days while the average (median) cost was

Febrile neutropenia and reduced dose intensity in patients with aggressive non-Hodgkin's lymphoma (NHL) treated with CHOP and CNOP

19,110 (

Hospitalization with febrile neutropenia in colorectal cancer patients

8,376) per episode. The 35% of patients hospitalized ≥ 10 days accounted for 74% of hospital days and 78% of total cost. Over the six years of observation, LOS decreased 10% while cost per day and total cost increased 28% and 13% respectively. Documented infection was reported in 38% of patients including sepsis in 19% and pneumonia in 10%. Death during hospitalization was reported in 11% of admissions. Mortality was most commonly associated with gram-negative sepsis (34%), pneumonia (27%) or comorbidities including renal (30%), cerebrovascular (30%), liver (28%) and lung disease (27%). Mortality rates increased with the number of comorbidities (P-trend<.001). Odds ratios for death were: gram-negative sepsis (4.8), pneumonia (2.4), renal (3.1), cerebrovascular (3.2), liver (2.9) and lung disease (3.9). Odds ratios for complicated hospitalization (length of stay ≥ 10 days) were: leukemia (3.4), gram-positive sepsis (2.5) and comorbidities with lung (2.1), renal (2.1), cerebrovascular (2.1) and liver disease (2.0) after adjustment for other comorbidities and infectious complications. CONCLUSIONS Hospitalization for FN is associated with considerable morbidity and mortality. Numerous patient characteristics, comorbidities and infectious complications are associated with increased mortality, length of stay and cost. [Table: see text].

Clinical Applications of G-CSF and GM-CSF in the Treatment of Infectious Diseases

6599 Background: Myelosuppression remains the major dose-limiting toxicity of systemic chemotherapy in patients with intermediate grade NHL. Recent studies support the importance of sustaining dose intensity in this setting. METHODS A survey of 1243 community oncology practices including nearly 5500 patients receiving chemotherapy for NHL was undertaken to evaluate the impact of demographic, clinical and treatment related factors on delivered dose intensity. Relative dose intensity (RDI) was estimated for each drug as the ratio of dose intensity received to standard dose intensity for each regimen. RESULTS This analysis is limited to 3536 patients with aggressive NHL (Working Formulation D-H) treated with CHOP (87%) or CNOP (13%) chemotherapy over a 10-year period from 1992 to 2001. Average age was 61 years with 45% ≥65 years and 54% male. Diffuse large cell histology was reported in 57%. Febrile neutropenia (FN) occurred one or more times in 21% of patients of which 76% required hospitalization. In multivariate analysis, significant risk factors for FN included age >65 (OR=1.8), female gender (OR=1.5), heart disease (OR=3.3), liver disease (OR=3.4) and ECOG performance status ≥2 (OR=2.1). Average RDI to reference standard was 84% with averaged planned and unplanned reductions in RDI of 4.5% and 11.5% respectively. Forty-five percent of patients received average RDI <85%. Risk factors for average RDI <85% included age ≥ 65 (53%), stage 4 (53%), ECOG performance status ≥ 2 (57%), female gender (48%), body mass index (BMI) ≥ 30 (50%) and hospitalization for FN (54%). Colony-stimulating factors were used in 41% of patients primarily in response to a previous episode of FN. In multivariate analysis, significant independent risk factors for average RDI <85% included age >65 (OR=1.8), female gender (OR=1.2), stage 4 (OR=1.6), CHOP (OR=1.3), BMI ≥30 (1.4) and previous FN hospitalization (1.4). CONCLUSIONS Nearly one-half of patients with aggressive NHL histology treated with CHOP-like regimens experienced substantial dose reductions related to age, stage, gender, obesity, regimen and previous FN hospitalization. [Table: see text].