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

The Journal of Community and Supportive Oncology. 2018 November;16(6):e260-e271 | 10.12788/jcso.0432
December 5, 2018|Hematology and Oncology
Chao et al
Author and Disclosure Information

Leila Family, PhD,a Hairong Xu, PhD,b Kim Cannavale, MPH,c Bhakti Mehta, MD,b Andrew Pourmoussa, MD,d Lanfang Xu, MS,e and Chun Chao, PhDc

aOffice of Health Assessment and Epidemiology, Los Angeles County Department of Public Health, Los Angeles, California, bAmgen Inc, Thousand Oaks, California, cDepartment of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California, dDepartment of Medicine, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California, eMedHealth Statistical Consulting Inc, Solon, Ohio

Background Chemotherapy-induced anemia (CIA) is associated with many symptoms that negatively impact quality of life. However, a systematic examination of symptoms in patients with CIA is lacking. 

Objective To describe the occurrence of a comprehensive list of symptoms in patients with stage IV malignancies by CIA status.
 
Methods Patients diagnosed with stage IV non-Hodgkin lymphoma, breast, and lung cancer at Kaiser Permanente Southern California (2010-2012) were eligible. CIA was defined as hemoglobin <10 g/dL after the initiation of chemotherapy. Standardized record review evaluated the occurrence of symptoms for all patients who developed CIA (n = 402), and a random sample of patients who did not develop CIA (n = 98). The prevalence of each symptom and the distribution of number of symptoms per patient were described overall and by anemia grade. 

Results Mean number of symptoms during chemotherapy for patients who did and did not develop CIA was 6.8 and 4.1, respectively (P < .01). Fatigue (90%), dyspnea or shortness of breath (58%), nausea or vomiting (56%), and loss of appetite (56%) were documented in >50% of patients who developed CIA, whereas only fatigue (77%) was noted in >50% patients without CIA. Several symptoms, including depression, diarrhea, dizziness or lightheadedness, and dyspnea, particularly demonstrated a clearly increasing prevalence with declining hemoglobin level. The mean number of symptoms per patient increased as CIA grade increased (3.6 symptoms for grade 2, and 5.4 symptoms for grades 3 and 4, respectively).

Limitations No causal relationship was examined due to descriptive design. 

Conclusions High-grade CIA correlates with an increased symptom burden in patients with stage IV malignancies. 

Funding Amgen Inc, maker of ESA used in the treatment of anemia

Accepted for publication October 26, 2018
Correspondence Chun Chao, PhD; Chun.R.Chao@kp.org
Disclosures Hairong Xu and Bhakti Mehta were employees of Amgen during study execution and received salary and stock as part of employment. Amgen provided research support to Kaiser Permanente to perform this study who, in turn, employed or contracted with the non-Amgen authors. Authors did not report any other potential conflicts of interest.

©2018 Frontline Medical Communications
doi https://doi.org/10.12788/jcso.0432

Limitations

In addition to the limitations already discussed, there are several others that should be considered when interpreting our results. We did not have a consistent measure of symptom severity in the medical records. Duration of symptoms was also often poorly documented by physicians. Therefore, our results are not directly comparable with studies such as the MDASI that incorporate severity or duration in their prevalence measure. There may also be “reporting bias” by the clinicians owing to different perceived levels of severity or clinical relevance of the different symptoms. As a result, some symptoms may be underdocumented, leading to undercounting.

We also did not distinguish the exact cause of the symptoms (ie, owing to anemia, cancer, chemotherapy itself, or other chemotherapy-induced complications), as it was not possible to reliably ascertain the cause from record review. Furthermore, symptom assessment was not separately performed for grade 4 anemia because of the small number of events in the study population. We also did not plan to evaluate the impact of anemia treatment on symptom burden, as our goal was to comprehensively describe a wide spectrum of symptoms experienced by patients with different Hb levels. However, previous studies have shown the benefit of treatments that correct CIA in symptom management.14-16 Finally, this study does not inform about the relative importance of these symptoms to patients’ quality of life. To this end, a qualitative study found fatigue, shortness of breath, and lightheadedness/dizziness to be the most important symptoms ranked by patients with CIA.22

Despite the potential limitations, our study has several important strengths. In addition to fatigue, patients with CIA suffer from a wide range of other anemia-related symptoms, but data on the prevalence of these symptoms have been lacking. To our knowledge, this is among the first studies that collected data on a comprehensive list of symptoms and provided detailed analysis by chemotherapy cycle and anemia grade. The combined use of KPSC’s clinical databases and medical record review allowed us to provide detailed characterization of the study population in terms of their treatment history, history of comorbidities, and laboratory data.
 

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Conclusions

Our data provide physicians a comprehensive picture of prevalence of various types of symptoms and how symptom burden evolves as chemotherapy cycle and anemia severity progress. High-grade CIA correlates with an increased symptom burden. Such an understanding can be crucial in facilitating supportive care planning by helping physicians anticipate the timing and proactively determine the management approach of chemotherapy-related anemia and its symptoms.

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