Debra A. Wolff

Acute Myeloid Leukemia or Myelodysplastic Syndrome in Randomized Controlled Clinical Trials of Cancer Chemotherapy With Granulocyte Colony-Stimulating Factor: A Systematic Review

PURPOSE To evaluate the risk of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and overall mortality in patients receiving chemotherapy with or without granulocyte colony-stimulating factor (G-CSF), a systematic review of randomized controlled trials (RCTs) was conducted. METHODS Electronic databases searched through October 2008 identified 3,794 articles for initial screening. Eligibility included solid tumor or lymphoma patients randomly assigned to chemotherapy with or without G-CSF support, > or = 2 years of follow-up, and reporting AML/MDS or all second malignancies. Dual blinded data extraction was performed. Relative risk (RR) and absolute risk (AR) estimates +/- 95% CIs were calculated by the Mantel-Haenszel method. RESULTS In the 25 eligible RCTs, 6,058 and 6,746 patients were randomly assigned to receive chemotherapy with and without initial G-CSF support, respectively. At mean and median follow-up across studies of 60 and 53 months, respectively, AML/MDS was reported in 22 control patients and 43 G-CSF-treated patients, with an estimated RR of 1.92 (95% CI, 1.19 to 3.07; P = .007) and AR increase of 0.41% (95% CI, 0.10% to 0.72%; P = .009). Deaths were reported in 1,845 patients randomly assigned to G-CSF and in 2,099 controls, for estimates of RR and AR decrease of 0.897 (95% CI, 0.857 to 0.938; P < .001) and 3.40% (95% CI, 2.01% to 4.80%; P < .001), respectively. Greater RR reduction for mortality was seen for both larger studies (P = .05) and greater chemotherapy dose-intensity (P = .012). CONCLUSION Delivered chemotherapy dose-intensity and risk of AML/MDS are increased but all-cause mortality is decreased in patients receiving chemotherapy with G-CSF support. Greater reductions in mortality were observed with greater chemotherapy dose-intensity.

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.

Dose Intensity and Hematologic Toxicity in Older Cancer Patients Receiving Systemic Chemotherapy

This prospective study was undertaken to evaluate patient and treatment characteristics that contribute to hematologic toxicity in older cancer patients.

Predicting Individual Risk of Neutropenic Complications in Patients Receiving Cancer Chemotherapy

A prospective cohort study was undertaken to develop and validate a risk model for neutropenic complications in cancer patients receiving chemotherapy.

The impact of the granulocyte colony-stimulating factor on chemotherapy dose intensity and cancer survival: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND The granulocyte colony-stimulating factor (G-CSF) is utilized to reduce neutropenic complications in patients receiving cancer chemotherapy. This study represents a systematic review and evidence summary of the impact of G-CSF support on chemotherapy dose intensity and overall mortality. MATERIALS AND METHODS All randomized controlled trials (RCTs) comparing chemotherapy with or without G-CSF support and reporting all-cause mortality with at least 2 years of follow-up were sought. Dual-blind data abstraction of disease, treatment, patient and outcome study results with conflict resolution by third party was carried out. RESULTS The search revealed 61 randomized comparisons of chemotherapy with or without initial G-CSF support. Death was reported in 4251 patients randomized to G-CSFs and in 5188 controls. Relative risk (RR) with G-CSF support for all-cause mortality was 0.93 (95% confidence interval: 0.90-0.96; P < 0.001). RR for mortality varied by intended chemotherapy dose and schedule: same dose and schedule (RR = 0.96; P = 0.060), dose dense (RR = 0.89; P < 0.001), dose escalation (RR = 0.92; P = 0.019) and drug substitution or addition (RR = 0.94; P = 0.003). Greater RR reduction was observed among studies with longer follow-up (P = 0.02), where treatment was for curative intent (RR = 0.91; P < 0.001), and where survival was the primary outcome (RR = 0.91; P < 0.001). CONCLUSIONS All-cause mortality is reduced in patients receiving chemotherapy with primary G-CSF support. The greatest impact was observed in RCTs in patients receiving dose-dense schedules.

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].

The impact of chemotherapy dose intensity and supportive care on the risk of febrile neutropenia in patients with early stage breast cancer: a prospective cohort study

BackgroundFebrile neutropenia (FN) is a major dose-limiting toxicity of cancer chemotherapy resulting in considerable morbidity, mortality, and cost. This study evaluated the time course of neutropenic events and patterns of supportive care interventions in patients receiving chemotherapy for early-stage breast cancer treated in oncology community practices.MethodsA prospective cohort study of adult cancer patients initiating a new chemotherapy regimen was conducted at 115 US sites. Toxicity associated with chemotherapy including neutropenic and infectious complications was recorded over four cycles. Clinical interventions were recorded including reductions in chemotherapy dose intensity and use of supportive care measures.ResultsA total of 1,202 patients with stage I–III breast cancer were evaluated. The majority of neutropenic (116 of 196) and infection events (179 of 325) occurred in the initial cycle. A decrease in occurrence of FN and infection was observed in the subsequent cycles, along with an increase in utilization of colony stimulating factors (CSFs), antibiotics and reductions in chemotherapy dose intensity. The overall risk of FN in all patients was 16.3%. In patients who started treatment at or near full dose intensity, the FN risk reached 21.0% without primary CSF prophylaxis and it was 9.0% with prophylaxis. There was no significant difference in FN rates by menopausal or hormone receptors status.ConclusionsThe risk of neutropenic complications is greatest in the initial cycle when most patients receive full-dose chemotherapy. A decrease in neutropenic events during subsequent cycles is associated with reduced dose intensity or increased use of supportive care measures. However, the cumulative risk of FN remains high in patients with early-stage breast cancer receiving full dose chemotherapy without prophylactic measures.