The doublet chemotherapy regimen contained one drug from one of the following categories: anthracycline (doxorubicin, epirubicin, mitoxantrone, liposomal doxorubicin), taxane (paclitaxel, docetaxel, nanoparticle albumin-bound -paclitaxel), platinum (cisplatin, carboplatin, not oxaliplatin), or gemcitabine. Chemotherapy episodes were re-indexed when the hemoglobin level was <10 g/dL to estimate the proportions of episodes and patients that further declined to hemoglobin <9 g/dL by 3, 6, and 9 weeks without ESA therapy.ĮMR-eligible patients could not have received an ESA within 9 weeks before the date when hemoglobin was 10 g/dL to 11 g/dL or at any time during the 18-week study period unless hemoglobin was <9 g/dL. Patients could be on any cycle of their chemotherapy regimen as long as they received ≥2 additional chemotherapy cycles at ≤35-day intervals after their index hemoglobin level of 10 g/dL to 11 g/dL. EMR-eligible patients also had received a myelosuppressive chemotherapy doublet (two chemotherapy drugs) between Augand June 26, 2010. To closely mirror the criteria of the RCTs, eligible patients in this analysis from the EMR database were ≥18 years old with nonmyeloid malignancies and index hemoglobin ≥10 g/dL and <11 g/dL on or after the start of the chemotherapy episode, with an index hemoglobin date between Augand June 26, 2010. In the original studies, patients had a baseline hemoglobin level of ≤11.0 g/dL in four studies, <11.0 g/dL in one study, and ≥9 g/dL in one study.
#Low hematocrit and hemoglobin in cancer patients trial#
The subset of placebo patients in these studies who had a baseline hemoglobin ≥10 g/dL and reported at least one hemoglobin value <10 g/dL during the study treatment period (length of trial was 16 weeks for five RCTs and 24 weeks for one RCT) were included in the analysis. The darbepoetin alfa RCTs included patients with solid tumors, lung cancer, lymphoproliferative malignancies, and multiple tumor types. As these data were up to 10 years old, we wanted to determine if these results would also be applicable to a contemporary USA patient population and therefore performed the same analysis using data from an EMR database transfusions are not routinely collected in outpatient EMRs, so the transfusion endpoint could not be evaluated in the patients in the EMR database. The purpose of this analysis was to estimate the proportion of patients from pooled data from six RCTs whose hemoglobin declined from a level of <10 g/dL to <9 g/dL and the proportion of patients who further declined to a level that required a transfusion in the absence of treatment with an ESA. RCTs with placebo control are usually considered the gold standard of clinical evidence however, results from these trials, which were initiated in the late 1990s, may not reflect real-world contemporary oncology care in 2012.
We examined rates of hemoglobin decline using two types of data: (1) from patients enrolled in randomized, placebo-controlled clinical trials (RCTs) and (2) from community oncology clinic electronic medical records (EMRs). A better understanding of factors that influence the rate of hemoglobin decline from 10 g/dL to 9 g/dL may assist oncologists in optimizing the use of ESAs in patients receiving chemotherapy. Few data are available regarding the proportion of patients with hemoglobin in the range of 9 g/dL to <10 g/dL who will experience a hemoglobin decline to <9 g/dL or the rate at which the decline occurs. However, not all patients whose hemoglobin is in the 9 g/dL to 10 g/dL range will continue to fall to levels of <9 g/dL, and because ESAs have risks, the decision of when to initiate an ESA is partially informed by the rate of hemoglobin decline and the likelihood that the patient will require a transfusion if they do not receive the ESA. Studies have suggested that initiating an ESA when hemoglobin is between 9 g/dL and 10 g/dL results in fewer transfusions compared with initiating an ESA when hemoglobin is <9 g/dL. However, ESAs take time to induce a hemoglobin response and therefore are not suitable for patients who require immediate correction of anemia. According to current ESA labels, treatment with ESAs in patients receiving chemotherapy should not be considered until hemoglobin levels are less than 10 g/dL in the USA or at or below 10 g/dL in the EU. Chemotherapy-induced anemia can be treated with erythropoiesis-stimulating agents (ESAs), red blood cell (RBC) transfusions, or both.
Anemia is common in cancer patients receiving chemotherapy and is associated with poor clinical outcomes.