Charles L. Bennett, MD, PhD; Samuel M. Silver, MD, PhD; Benjamin Djulbegovic, MD, PhD; Athena T. Samaras, BA; C. Anthony Blau, MD; Kara J. Gleason, BS; Sara E. Barnato, MD; Kathleen M. Elverman; D. Mark Courtney, MD; June M. McKoy, MD, MPH, JD; Beatrice J. Edwards, MD; Cara C. Tigue, BA; Dennis W. Raisch, PhD; Paul R. Yarnold, PhD; David A. Dorr, MD, MS; Timothy M. Kuzel, MD; Martin S. Tallman, MD; Steven M. Trifilio, RPh; Dennis P. West, PhD; Stephen Y. Lai, MD, PhD; Michael Henke, MD
JAMA. 2008;299(8):914-924.
Context The erythropoiesis-stimulating agents (ESAs) erythropoietinand darbepoetin are licensed to treat chemotherapy-associatedanemia in patients with nonmyeloid malignancies. Although systematicoverviews of trials have identified venous thromboembolism (VTE)risks, none have identified mortality risks with ESAs.
Objective To evaluate VTE and mortality rates associatedwith ESA administration for the treatment of anemia among patientswith cancer.
Data Sources A published overview from the Cochrane Collaboration(search dates: January 1, 1985-April 1, 2005) and MEDLINE andEMBASE databases (key words: clinical trial, erythropoietin,darbepoetin, and oncology), the public Web site of the US Foodand Drug Administration and ESA manufacturers, and safety advisories(search dates: April 1, 2005-January 17, 2008).
Study Selection Phase 3 trials comparing ESAs with placeboor standard of care for the treatment of anemia among patientswith cancer.
Data Extraction Mortality rates, VTE rates, and 95% confidenceintervals (CIs) were extracted by 3 reviewers from 51 clinicaltrials with 13 611 patients that included survival informationand 38 clinical trials with 8172 patients that included informationon VTE.
Data Synthesis Patients with cancer who received ESAshad increased VTE risks (334 VTE events among 4610 patientstreated with ESA vs 173 VTE events among 3562 control patients;7.5% vs 4.9%; relative risk, 1.57; 95% CI, 1.31-1.87) and increasedmortality risks (hazard ratio, 1.10; 95% CI, 1.01-1.20).
Conclusions Erythropoiesis-stimulating agent administrationto patients with cancer is associated with increased risks ofVTE and mortality. Our findings, in conjunction with basicscience studies on erythropoietin and erythropoietin receptorsin solid cancers, raise concern about the safety of ESA administrationto patients with cancer.
Advanced cancer in the setting of liver dysfunction poses a dilemma for physicians, as many cancer chemotherapeutic agents undergo hepatic metabolism. Most cytotoxic drugs have a narrow therapeutic index, and the administration of chemotherapy to patients with liver impairment results in complicated safety issues. We present a concise review of cancer chemotherapy dosing in the setting of liver dysfunction. Although caution in treating all patients with hepatic failure is essential, the use of certain agents provokes greater concern than others. Continuous-infusion fluorouracil, capecitabine (Xeloda), mechlorethamine (Mustargen), cyclophosphamide, topotecan (Hycamtin), and oxaliplatin (Eloxatin) appear to be relatively well tolerated. On the contrary, taxanes, vinca alkaloids, irinotecan (Camptosar), and anthracyclines may cause unacceptable toxicity if administered to patients with poor hepatic function. For many anticancer agents, the paucity of data prohibits formal dosing recommendations, and most guidelines remain empiric. 相似文献
Zygomycosis is increasingly reported as a cause of life-threatening fungal infections. A higher proportion of cases reported over the last decades have been in cancer patients, with or without hematopoietic stem cell transplantation (HSCT). The new anti-fungal agent voriconazole is a recently identified risk factor for developing zygomycosis. We reviewed the clinical characteristics and outcomes of a large cohort of cancer patients who developed zygomycosis after exposure to voriconazole. Health care professionals at 13 large cancer centers provided clinical information on cancer patients with zygomycosis and prior exposure to voriconazole. Criteria for inclusion were 5 days or more of voriconazole use and diagnostic confirmation with tissue or histology. Fifty-eight cases were identified among patients with hematologic malignancies, 62% including patients who underwent a HSCT procedure. Fifty-six patients received voriconazole for primary or secondary prophylaxis against fungal infection. In addition to prior exposure to voriconazole, patients also had several of the previously established risk factors for zygomycosis. Amphotericin B was the most commonly prescribed anti-fungal therapy. Overall mortality was 73%. We conclude that zygomycosis after exposure to voriconazole is a recently described entity that is frequently fatal, despite treatment with currently available anti-fungal agents and surgery. 相似文献
Purpose. Febrile neutropenia (FN) is a common, costly, and potentially fatal complication in oncology. While FN in the inpatient setting has been extensively studied, only one study has evaluated emergency department (ED) care for FN cancer patients. That study found that 96% of patients survived the complication. We evaluated clinical and economic outcomes for cancer patients with chemotherapy-associated FN treated in an ED. Methods. ED records for consecutive oncology patients with FN were reviewed for information on death, intensive care unit (ICU) use, blood cultures, and costs. Results. Forty-eight patients (n = 57 visits) were evaluated. Six patients died from FN (12%) and four received ICU care within 2 weeks and survived (8%). Blood cultures were positive for 37% of the ED visits. The median ED time was 3.3 hours. In 91% of visits, i.v. antibiotics were administered in the ED, ordered at a median of 1.7 hours from triage (interquartile range [IQR], 1.2-2.8 hours). All patients with death or ICU in 2 weeks and all but one patient with positive blood cultures received antibiotics. The median per patient ED costs were $1,455 (IQR, $1,300-$1,579)-42.4% for hospital/nursing, 23.5% for radiology, 20.8% for physician services, 10.9% for diagnostic tests, and 2.4% for antibiotics. Conclusions. Cancer patients with FN in this sample presenting to the ED frequently had no identified source of infection. One third of the patients had positive ED blood cultures and one fifth died or required ICU care within 2 weeks. Costs of ED care were similar to the cost of a single day of inpatient care. Disclosure of potential conflicts of interest is found at the end of this article. 相似文献
Mitoxantrone and etoposide (ME) salvage regimens have been successfully used for the treatment of primary induction failure or relapsed acute myeloid leukemia (AML). Whether the addition of intermediate dose cytarabine to ME increases complete remissions is unknown. To date, these regimens have not been directly compared. Herein, we report the response to treatment with a fixed dosing schedule of ME or MEC in 65 patients treated for primary refractory or relapsed AML with intermediate or unfavorable risk cytogenetics. Differences in CR between ME and MEC subsets were analyzed to determine the effect of cytarabine to ME. 相似文献
Growth factors are routinely used after autotransplantation to accelerate hematopoietic recovery, and are continued until the absolute neutrophil count (ANC) is >/=0.5 x 10(9)/l on 3 consecutive days. Since ANC often increases to very high levels with this strategy, we discontinued growth factor on the first day ANC reached 0.5 x 10(9)/l in 45 patients (Study Group), and compared their subsequent ANC to 108 historic controls who received growth factor longer. While ANC on the day after reaching 0.5 x 10(9)/l was comparable between groups, ANC on the third day was significantly higher in the Control Group (2.3 vs 4.9 x 10(9)/l; P=0.0003). When compared to the first day, ANC in the Study Group was higher by a median of 140% on the third day and by 450% in the Control Group (P=0.0002). A significantly higher proportion of patients experienced a decline in ANC after the first day in the Study Group. However, only one patient in the Study Group became neutropenic transiently and ANC recovered spontaneously the next day. The incidence of fever and hospitalization were comparable. We conclude that growth factors can be discontinued after autotransplantation the day the ANC reaches 0.5 x 10(9)/l, without compromising neutrophil recovery. 相似文献
After a hospital‐wide formulary change resulted in the replacement of filgrastim with TBO‐filgrastim for all on‐ and off‐label indications, we performed a retrospective comparison of patients with myeloma receiving 200 mg/m2 melphalan with autologous hematopoietic stem cell transplantation to see whether the type of growth factor used post‐transplant made a difference. One hundred and eighty‐two consecutive patients with myeloma were studied, 91 receiving filgrastim immediately prior to the change and 91 receiving TBO‐filgrastim afterward. The CD34+ cell dose was comparable, as were other characteristics. Although the overall time to neutrophil recovery was similar for both groups, early engraftment (≤12 d) occurred more often (p = 0.05), and late engraftment (≥14 d) less often (p = 0.09) in filgrastim‐treated patients. The number of documented infections was significantly less in the TBO‐filgrastim group. Day 100 mortality and hospital stay were similar for the two groups. These data indicate that there is no material difference between filgrastim and TBO‐filgrastim in this clinical setting. 相似文献
More than half of all serious adverse reactions are identified 7 or more years after a drug receives approval from the US Food and Drug Administration (FDA). In 2002, 9 months after the intravenous bisphosphonate zoledronic acid received regulatory approval for marketing, the FDA received reports of nine patients with cancer, who were treated with zoledronic acid, who unexpectedly developed osteonecrosis of the jaw. During the next 2 years, three oral surgeons described 104 patients with cancer with osteonecrosis of the jaw in the medical literature and identified intravenous bisphosphonate therapy as being common to the care of these patients. In subspecialty medical, radiology, and dental journals, case reports and case series described clinical features of osteonecrosis of the jaw in patients with cancer who were treated with bisphosphonates. Manufacturer-sponsored epidemiological studies reported the first estimates of the incidence of this toxic effect, ranging from 0·1% to 1·8%. By contrast, independent epidemiological efforts from clinicians and the International Myeloma Foundation reported incidence estimates between 5% and 10%. Between 2003 and 2005, warnings about the risks of bisphosphonate-associated osteonecrosis were disseminated by national regulatory agencies, the manufacturers of bisphosphonates, and the International Myeloma Foundation. From 2006, independent clinical recommendations for diagnosis, prevention, and treatment of this toxic effect have been disseminated by manufacturers, national regulatory authorities, the International Myeloma Foundation, and medical specialty organisations. Furthermore, independent efforts by pharmaceutical manufacturers, dental and medical professionals, a non-profit organisation (the International Myeloma Foundation), patients, and regulatory authorities has led to the rapid identification and dissemination of safety information for this serious adverse reaction. Better coordination of safety-related pharmacovigilance initiatives is now needed. 相似文献