Severe Fatigue During the Palliative Treatment Phase of Cancer

An Exploratory Study

Marlies E. W. J. Peters, MSc, RN; Martine M. Goedendorp, PhD; Constans A. H. H. V. M; Verhagen, MD, PhD; Winette T. A. van der Graaf, MD, PhD; Gijs Bleijenberg, PhD


Cancer Nurs. 2014;37(2):139-145. 

In This Article

Abstract and Introduction


Background: Because of a rise in incidence and more effective treatments, the prevalence of patients with metastatic cancer is increasing fast. When palliative treatment is aimed at maintaining or improving patients' quality of life, knowledge about severe fatigue is clinically relevant because of its debilitating effect, but at present this information is lacking.

Objective: This study investigated the prevalence of severe fatigue in patients with various incurable cancers and whether severe fatigue increased with further treatment lines and differed between various cancers and treatment modalities. In addition, a relationship between severe fatigue and other symptoms was examined.

Methods: Patients were asked to fill in the Checklist Individual Strength, European Organization of Research and Treatment of Cancer–Quality of Life Questionnaire C30, and the McGill Pain Questionnaire during palliative anticancer treatment, and hemoglobin levels were collected.

Results: Of all participating patients (n = 137), 47% were severely fatigued. Patients who received first line of treatment were significantly less often severely fatigued (40%) compared with patients who received further lines (60%). Significantly more severe fatigue was observed when patients had more pain, dyspnea, appetite loss, nausea, vomiting, and constipation.

Conclusions: During the phase of palliative anticancer treatment, fatigue was the most common symptom, nearly half of the patients had severe fatigue increasing with further treatment lines. Various treatment-related symptoms were related to more severe fatigue.


Implications for Practice: As severe fatigue is significantly related to other symptoms of cancer and its treatment, the screening and treatment of these cancer-related symptoms should be more stringent, as they might negatively influence each other.

Forty percent of cancer patients will experience a relapse of their disease; some patients have incurable cancer from the first diagnosis. Cancer care of patients with incurable disease is primarily aimed at prolonging the patients' life and managing symptoms to maintain or improve patients' quality of life. In recent years, more effective medicines have been developed to treat cancer and the symptoms of cancer in all phases of the disease. In some advanced cancers, care has led to life prolongation in years,[1–3] but more typically the progress has been gradual with an increase in treatment options. Because of the longer survival rates, the prevalence of cancer patients with advanced disease is increasing. There are various standard therapies for patients with advanced, incurable cancer such as chemotherapy, hormonal therapy, radiotherapy, immunotherapy, and targeted therapy given as single-agent therapy or in different combinations. With the introduction of new oral targeted agents, the treatment adverse effects have an impact on patients' daily quality of life. In contrast to the relatively short, cyclic, and sometimes serious adverse effects of antineoplastic drugs, the adverse effects of oral targeted agents are continuously present and influencing daily quality of life.[4,5]

Fatigue is known to be one of the most distressing symptoms for patients with cancer and adversely affects patients' daily quality of life.[6–14] Prevalence rates up to 99% in patients with advanced, incurable cancer are mentioned.8–11,15 Cancer-related fatigue is defined as "a distressing persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning."[16] Severe fatigue can be considered an extreme degree of fatigue with a profound, debilitating effect on daily life and should therefore be seen as a clinically relevant symptom.

Many studies on fatigue in cancer patients have been carried out in patients during treatment with curative intent and in survivors, but there is limited knowledge about the severity of fatigue and related factors in patients with advanced cancer. Fatigue is an underrecognized, underassessed, and undertreated symptom in this group of patients Some consider fatigue an unavoidable symptom, caused by the disease itself or by adverse effects of anticancer treatment. However, studies confirming this are lacking.[4,8,10,11,17,18] Therefore, we found it important to study severe fatigue in patients with advanced cancer in an exploratory way. Moreover, more knowledge is warranted to find starting points to develop effective interventions for severe fatigue in these patients.

It is striking that studies of fatigue in patients with incurable cancer pooled the data of all patients at different phases of the palliative trajectory up to the terminal phase.[15,19,20] As a result, these studies cannot provide insight to severe fatigue in the various phases of palliative cancer treatment trajectory. Several studies involving palliative cancer patients documented that 2 treatments (chemotherapy and radiotherapy) were positively associated with fatigue.[15,21–23] Oral targeted therapy as reported in 2 studies was associated with fatigue in patients with advanced and metastatic renal cell carcinoma.[5,24] In 1 study involving palliative patients with prostate cancer, hormonal therapy showed a relation with fatigue.[25] It is unclear whether fatigue is more common in certain treatment modalities, whether a cumulative effect exists, or whether progression of the disease itself contributes to fatigue.

Cancer and its treatment as well as other factors can contribute or cause fatigue. For example, hemoglobin (Hb) level has been examined, but mixed findings have been reported in terms of it being a causative factor to fatigue.[8,26,27] In the study of Yennurajalingam et al,[7] a significant association with fatigue and several other cancer-related symptoms, such as pain, dyspnea, insomnia, anorexia, and drowsiness, was described. Others have focused on a decrease in the quality of life and investigated the experience of other cancer-related symptoms, including fatigue in association with quality of life.[5,7,28,29]

The main aim of this study was to investigate the prevalence of severe fatigue in patients with advanced, incurable cancer. We also aimed to investigate whether certain malignancies, treatment modalities, or further line of treatment had a higher occurrence of severe fatigue. Furthermore, we examined whether there was a relationship between severe fatigue and other cancer- and treatment-related symptoms. The following research questions were formulated:

  1. What is the occurrence of severe fatigue in patients with advanced, incurable cancer during cancer treatment in the palliative phase?

  2. Are patients who are receiving the first treatment line of palliative treatment less likely to have severe fatigue as compared with patients receiving subsequent treatment lines of palliative treatment?

  3. Does the occurrence of severe fatigue differ among types of cancers and/or treatment modalities?

  4. Do severely fatigued cancer patients have more other cancer-related symptoms such as dyspnea, pain, loss of appetite, nausea, vomiting, constipation, diarrhea, and anemia?