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.

BACKGROUND: Febrile 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. METHODS: A 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. RESULTS: A 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. CONCLUSIONS: The 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.

Predicting individual risk of neutropenic complications in patients receiving cancer chemotherapy.

BACKGROUND: A prospective cohort study was undertaken to develop and validate a risk model for neutropenic complications in cancer patients receiving chemotherapy. METHODS: The study population consisted of 3760 patients with common solid tumors or malignant lymphoma who were beginning a new chemotherapy regimen at 115 practice sites throughout the United States. A regression model for neutropenic complications was developed and then validated by using a random split-sample selection process. RESULTS: No significant differences in the derivation and validation populations were observed. The risk of neutropenic complications was greatest in cycle 1 with no significant difference in predicted risk between the 2 cohorts in univariate analysis. After adjustment for cancer type and age, major independent risk factors in multivariate analysis included: prior chemotherapy, abnormal hepatic and renal function, low white blood count, chemotherapy and planned delivery ≥85%. At a predicted risk cutpoint of 10%, model test performance included: sensitivity 90%, specificity 59%, and predictive value positive and negative of 34% and 96%, respectively. Further analysis confirmed model discrimination for risk of febrile neutropenia over multiple chemotherapy cycles. CONCLUSIONS: A risk model for neutropenic complications was developed and validated in a large prospective cohort of patients who were beginning cancer chemotherapy that may guide the effective and cost-effective use of available supportive care.

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.

Dose intensity and hematologic toxicity in older breast cancer patients receiving systemic chemotherapy.

BACKGROUND: This prospective study evaluated patient and treatment characteristics that contributed to hematologic toxicity in older breast cancer patients treated with curative intent in the community setting. METHODS: Data were collected on 1224 patients with stage I through III breast cancer, of whom 207 were aged > or =65 years (grading determined according to the American Joint Committee on Cancer staging system). Primary outcome measures included anemia, thrombocytopenia, severe neutropenia, febrile neutropenia, and both planned and actual relative dose intensity (RDI). Comparisons between older and younger patients regarding hematologic toxicity and reductions in RDI were based on univariate and multivariate logistic regression analyses. RESULTS: The neutropenic complication rate in older patients (45.1%) was not significantly different from that in the younger patients (43.7%). There were also no significant differences in rates of anemia or thrombocytopenia. Approximately 34.0% of the older patients received RDI <85% compared with 20.0% among younger patients (P < .01). Fewer older patients received anthracycline-based chemotherapy (64.3% compared with 83.8% in younger patients, P < .01). Fewer older patients received prophylactic white blood cell colony-stimulating factor (18.4%) compared with younger patients (28.0%) (P < .01). CONCLUSIONS: There were no significant differences noted with regard to chemotherapy-related hematologic toxicities between older and younger breast cancer patients in this large prospective observational study. This may be explained, in part, by more frequent reductions in RDI and less frequent utilization of anthracyclines among older patients.

Variation in the cost of medications for the treatment of colorectal cancer.

OBJECTIVE: To evaluate the economic burden of colorectal cancer (CRC) treatment on the healthcare system as treatment costs have risen 340-fold during the past 5 years. STUDY DESIGN: Nationwide registry. METHODS: Patients with CRC (N = 421) were selected from an observational prospective patient registry of US oncology clinics. The 8 most commonly prescribed regimens were identified. Standard dosing schedules were set for these regimens based on a literature review and expert CRC oncologist input. Each chemotherapeutic regimen was broken down into its component agents, and regimen costs were calculated by summing the costs of each agent per regimen. Price-per-milligram costs were calculated from Health Care Financing Administration Common Procedural Coding System codes for specific drugs. Patient population, temporal, and regional trends were studied among standard regimens. RESULTS: The most common regimens were 5-fluorouracil-leucovorin calcium (5-FU/LV) (147 patients [34.9%]), fluorouracil-leucovorin-irinotecan hydrochloride (FOLFIRI) (111 patients [26.4%]), and fluorouracil-leucovorin-oxaliplatin (103 patients [24.5%]). The remaining 60 patients (14.3%) received irinotecan, capecitabine, and oxaliplatin; oxaliplatin; irinotecan in combination with oxaliplatin; or a miscellaneous regimen. The largest cost differential for 6 cycles of planned treatment was $35,971 between FOLFIRI ($36,999) and 5-FU/LV ($1028). On a per-week basis, treatment costs may differ by more than 91 times. Patient utilization of growth factors, ancillary medications, and monoclonal antibodies added significant costs. CONCLUSIONS: The costs of CRC regimens varied considerably. Trends in treatment regimens have changed notably over time, with newer agents and supportive drugs adding substantially to treatment costs.

Risk and timing of neutropenic events in adult cancer patients receiving chemotherapy: the results of a prospective nationwide study of oncology practice.

This study was undertaken to describe the relationship between the occurrence and timing of neutropenic events and chemotherapy treatment in a community-based population of patients with cancer. The study included 2962 patients with breast, lung, colorectal, lymphoma, and ovarian cancers from a prospective U.S. registry of patients initiating a new chemotherapy regimen. Detailed patient-, disease-, and treatment-related data, including toxicities, were captured at baseline, the beginning of each cycle, and each midcycle blood draw for up to 4 cycles of treatment. Primary outcomes included febrile neutropenia (FN), severe neutropenia without fever/ infection, and relative dose intensity (RDI). Thirty-seven percent of patients were aged 65 years or older, 43.5% had an Eastern Cooperative Oncology Group performance status of 1 or greater, and 27% had 1 or more comorbidities. Reductions in RDI to less than 85% of standard in the first cycle were planned in 23.6% of patients, whereas primary colony-stimulating factor prophylaxis was used in 18.2%. In the first 3 cycles of treatment, 10.7% of patients experienced FN, with most of these events (58.9%) occurring in the first cycle. This first-cycle pattern was consistently observed despite wide variations in event rates by tumor type, disease stage, chemotherapy regimen and dose, and patient characteristics. Despite frequent planned reductions from standard RDI, the incidence of FN remains high in community oncology practice in the United States. Improved methods of pretreatment assessment of patient risk factors for neutropenia are needed.

Dose intensity and hematologic toxicity in older cancer patients receiving systemic chemotherapy.

BACKGROUND: This prospective study was undertaken to evaluate patient and treatment characteristics that contribute to hematologic toxicity in older cancer patients. METHODS: A nationwide study of 115 community oncology practices was conducted between 2002 and 2005 with data collected on 976 patients who had received chemotherapy for common malignancies, including lung cancer, colorectal cancer, breast cancer, ovarian cancer, genitourinary cancer, and lymphoma. Primary outcomes included severe neutropenia (SN) and febrile neutropenia (FN). Secondary outcomes included delivered relative dose intensity (RDI) <85%, dose delays > or =15% days, and reductions > or =15%. RESULTS: Approximately 50% of both patients with early-stage disease and patients with advanced-stage disease received an actual RDI <85%, and this rate reached 60% in the oldest group (aged >80 years). Increasing age was associated with lower actual RDI (P = .030) and averaged 87.5% across all elderly age groups. A decreasing trend in SN or FN events occurred with increasing age (P for trend = .039), with the majority of initial neutropenic events occurring in Cycle 1 for all age groups. Among the patients who received an actual RDI > OR =85%, there was no significant difference in SN or FN by age group or disease stage. Independent risk factors for the development of SN or FN included cancer type, planned RDI > or =85%, body surface area < or =2m(2), anthracycline- or platinum-based regimens, previous chemotherapy, elevated blood urea nitrogen, and alkaline phosphatase. Neutropenic complications decreased significantly with primary colony-stimulating factor (CSF) prophylaxis (coefficient of determination [R(2)] = 0.260; c-statistic = 0.782). CONCLUSIONS: Among cancer patients aged > or =70 years, 50% of whom received relatively full-dose chemotherapy, increasing age alone did not increase the risk of hematologic toxicity.

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.

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.