Helen Collins

Benefits and risks of using erythropoiesis-stimulating agents (ESAs) in lung cancer patients: study-level and patient-level meta-analyses.

In anemic patients receiving myelosuppressive chemotherapy, erythropoiesis-stimulating agents (ESAs) raise hemoglobin levels and reduce transfusion requirements, but ESA-related safety concerns exist. To evaluate ESA benefits and risks in lung cancer, we conducted meta-analyses of data from controlled ESA trials conducted in lung cancer patients. Study-level analyses included controlled ESA trials reporting lung cancer mortality, identified from the 2006 Cochrane ESA report and from a systematic search for studies published through December 2010. Patient-level analyses included data from lung cancer patients receiving chemotherapy in Amgen studies evaluating darbepoetin alfa (DA) vs placebo. Study-level and patient-level analyses examined deaths, progression, and transfusion incidence. Patient-level analyses also examined adverse events (AEs) and fatigue. In a study-level meta-analysis of nine ESA studies of 2342 patients receiving chemotherapy, the ESA odds ratio (OR) was 0.87 (95% confidence interval [CI] 0.69-1.09) for mortality; the overall random-effects risk difference (95% CI) for mortality was -0.02 (-0.06, 0.02). The ESA OR (95% CI) for disease progression in five chemotherapy studies reporting progression was 0.84 (0.65-1.09). The ESA odds ratio (95% CI) was 0.34 (0.28-0.41) for transfusion incidence. In a patient-level meta-analysis of four studies evaluating 1009 patients through follow-up, the median survival time was 41 weeks with DA and 38 weeks with placebo. During the combined study and follow-up periods, 80% of placebo-group patients and 74% of DA patients died (mortality hazard ratio [HR] 0.90 [95% CI, 0.78-1.03] for DA); results were similar for small cell lung cancer and non-small cell lung cancer. Overall, 87% of placebo patients and 84% of DA patients progressed or died. Fewer DA patients had transfusions (week 5 through end-of-study, DA 19%, placebo 43%). AEs included thrombotic/embolic events (DA 10.5%, placebo 7.2%), cerebrovascular disorders (DA 3.7%, placebo 4.2%), pulmonary edema (DA 0.4%, placebo 1.0%) and pulmonary embolism (DA 1.8%, placebo 0.6%). These meta-analyses suggest that ESAs reduce transfusions without increasing mortality or disease progression in lung cancer patients undergoing chemotherapy.

Progress in detecting cell-surface protein receptors: the erythropoietin receptor example

Testing for the presence of specific cell-surface receptors (such as EGFR or HER2) on tumor cells is an integral part of cancer care in terms of treatment decisions and prognosis. Understanding the strengths and limitations of these tests is important because inaccurate results may occur if procedures designed to prevent false-negative or false-positive outcomes are not employed. This review discusses tests commonly used to identify and characterize cell-surface receptors, such as the erythropoietin receptor (EpoR). First, a summary is provided on the biology of the Epo/EpoR system, describing how EpoR is expressed on erythrocytic progenitors and precursors in the bone marrow where it mediates red blood cell production in response to Epo. Second, studies are described that investigated whether erythropoiesis-stimulating agents could stimulate tumor progression in cancer patients and whether EpoR is expressed and functional on tumor cells or on endothelial cells. The methods used in these studies included immunohistochemistry, Northern blotting, Western blotting, and binding assays. This review summarizes the strengths and limitations of these methods. Critically analyzing data from tests for cell-surface receptors such as EpoR requires understanding the techniques utilized and demonstrating that results are consistent with current knowledge about receptor biology.

Transfusions and patient burden in chemotherapy-induced anaemia in France:

Objectives: To estimate the patient burden in terms of the time spent on outpatient red blood cell (RBC) transfusions indicated for chemotherapy induced-anaemia (CIA) in patients with cancer in France. Methods: A retrospective chart review of patients with cancer receiving an outpatient RBC transfusion was conducted at seven treatment centres in France. Total treatment time for one transfusion visit per patient was measured as the elapsed time between pre- and post-transfusion vital sign assessment, including time from transfusion start to stop. Elapsed time from haemoglobin (Hb) level testing to transfusion start and from blood draw for compatibility testing to transfusion start were recorded. In addition, estimated travel time and distance to the transfusion centre, and clinical and demographic information were collected. Results: A total of 103 patients [63.1% men; mean age 66.2 years, standard deviation (SD) 11.9] were enrolled in the study (1 August 2010–31 October 2010). The four most frequent diagnoses were lung cancer (31.1%), urological cancer (15.5%), gynecological cancer (14.6%) and gastrointestinal/colorectal cancer (14.6%). Mean elapsed time between prevital and postvital sign assessment was 4.0 h [95% confidence interval (CI) 1.9–6.1], including a mean of 3.4 h (95% CI 2.5–4.2) for the transfusion itself. Hb level testing (mean pre-transfusion Hb level 8.0 g/dl, SD 0.8) and blood draw for compatibility testing were completed in a mean of 28.8 h (95% CI 1.3–56.2) and 9.4 h (95% CI 0–21.4) prior to transfusion respectively. Patients’ one-way mean travel time to the transfusion centre was 32.9 min (95% CI 28.5–37.4) and mean distance travelled was 25.4 km (95% CI 11.6–39.3). Conclusion: In France, CIA treatment with RBC transfusion is a time-consuming activity for patients that includes multiple trips to a medical facility, blood testing and the transfusion procedure itself. This burden is important to consider in the context of optimizing proactive monitoring and planning for supportive oncology care.