Symptom burdens related to chemotherapy-induced anemia in stage IV cancer

Anemia is a common complication of cancer treatment as well as of cancer itself. Most cancer patients undergoing chemotherapy experience anemia sometime during their treatment course.^1,2 Moderate to severe anemia is associated with an array of symptoms that are known to compromise the physical functioning and quality of life of cancer patients. Common anemia-related symptoms include fatigue, drowsiness, depression, dyspnea, tachycardia, and dizziness.^1,3-7

Symptoms produced by cancer itself or the disease treatment (ie, side effects such as anemia) collectively compose a patient’s symptom burden.⁸ Although the occurrence of anemia-related fatigue has been described more systematically, other clinical presentations of chemotherapy-induced anemia (CIA) are not well characterized. Furthermore, the overall symptom burdens associated with different ranges of hemoglobin (Hb) concentrations have also not been well reported. Although various tools have been developed to facilitate the reporting of fatigue and other symptoms experienced by patients with CIA, such as the Functional Assessment of Cancer Therapy-Anemia (FACT-An) questionnaire and the MD Anderson Symptom Inventory (MDASI),^9-11 these questionnaires have not been extensively used outside of the research context. As such, knowledge on symptom burdens associated with CIA in real-world patient populations remains lacking.

Given the common occurrence of CIA, management of CIA and associated symptoms plays an important role to patients’ quality of life during cancer treatment. Symptom control is often the main goal for patients with stage IV cancers, as treatment for disease is most likely palliative or noncurative. To facilitate supportive care planning, it is important to understand patient symptom burdens as chemotherapy progresses over cycles and Hb levels decline. We conducted a comprehensive medical record review study in patients diagnosed with stage IV non-Hodgkin lymphoma (NHL), breast cancer, and lung cancers at Kaiser Permanente Southern California (KPSC), a large community-based health care delivery system. The objective of this study was to report the occurrence of CIA-related symptoms throughout the course of chemotherapy and by Hb levels.
 

Methods

Study setting and population

KPSC is an integrated managed-care organization that provides comprehensive health services for 4 million racially, ethnically, and socioeconomically diverse members who broadly represent the population in Southern California.¹² The organization maintains electronic records of health care received by its members, including physician record notes and clinical databases such as laboratory test results, diagnosis codes, medical procedures, medication dispenses, and disease registries. KPSC’s cancer registry is Surveillance, Epidemiology, and End Results, which is affiliated and routinely collects information on age, sex, race and/or ethnicity, cancer type, histology, and stage at diagnosis.

Patients who met the following inclusion criteria were included in this study: diagnosed with stage IV NHL, breast cancer, or lung cancer at age 18 years or older at KPSC between March 25, 2010 and December 31, 2012; initiated myelosuppressive chemotherapy at KPSC before June 30, 2013 (only the first chemotherapy course was included in this evaluation); and had at least 1 Hb measurement during the course of chemotherapy. Of those who met the inclusion criteria, patients who met the following criteria were excluded if they had less than 12 months KPSC membership before start of chemotherapy, missing information on cancer stage or chemotherapy regimen/agents, a diagnosis of myelodysplastic syndrome before chemotherapy initiation, a diagnosis of inherited anemia, an Hb concentration <10 g/L within 3 months before chemotherapy initiation, a transfusion within 2 weeks before chemotherapy initiation, radiation within 4 months before chemotherapy initiation, or bone marrow transplantation within 12 months before chemotherapy initiation or during the chemotherapy course. These exclusion criteria were applied to evaluate symptom burdens most likely related to CIA as opposed to other cancer treatment or pre-existing anemia.

CIA in this study was defined as moderate to severe anemia with Hb <10 g/dL after chemotherapy initiation. Based on this definition for CIA, all patients who developed CIA between the first chemotherapy administration to 60 days after the last dose of chemotherapy were included for the record review. In addition, a random sample of 100 patients who did not develop CIA (ie, did not reach an Hb <10 g/dL during chemotherapy) but otherwise met study eligibility criteria was also reviewed to serve as a comparison group. Of those, 2 patients were subsequently excluded after record review because of findings of ineligibility, so only 98 patients were presented. The large number of patients (ie, >4,000) who did not develop CIA made record review of all patients infeasible.