Treatment-related fatigue with sorafenib, sunitinib and pazopanib in patients with advanced solid tumors: An up-to-date review and meta-analysis of clinical trials

Abstract

Fatigue is the most common symptom associated with cancer and cancer treatment. We performed an up-to-date meta-analysis to determine the incidence and relative risk (RR) of fatigue in patients (pts) with cancer treated with sorafenib (SO), sunitinib (SU) and pazopanib (PZ). PubMed databases were searched for articles published till August 2013. Eligible studies were selected according to PRISMA statement. Summary incidence, RR and 95% confidence intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. Fifteen studies were included in our analysis. A total of 6,996 pts was enrolled: 2,260 had renal cell carcinomas (RCC), 1,691 non-small cell lung cancers, 1,290 breast cancers, 823 hepatocellular carcinomas, 362 soft tissue sarcomas, 304 gastrointestinal solid tumors, 165 neuroendocrine tumors and 101 melanomas. When stratified by drug, SO registered lower incidence and RR of all and high-grade fatigue when compared to SU, whereas the difference between SO and PZ was significant only for all-grade fatigue (p < 0.001). The difference between SU and PZ was significant for high-grade (p < 0.001) but not for all-grade fatigue (p 5 0.52). In RCC pts, PZ showed the lower incidence and RR of all and high-grade fatigue. The differences were significant for SU vs. SO (p < 0.001), SU vs. PZ (p < 0.001) and SO vs. PZ (p < 0.001). Treatment with SO, SU and PZ is associated with an increased incidence of fatigue in pts with cancer. Early and appropriate management is required to avoid unnecessary dose reductions and transitory or definitive treatment discontinuations.Fatigue is the most common symptom associated with cancer and cancer treatment. It is a subjective symptom characterized by a pervasive and persistent sense of body tiredness, exhaustion, depression, feeling unwell, loss of motivation and reduced capacity for mental work, which are unrelated to activity or exertion. This condition can negatively impact the functional status and the health-related quality of life (HRQoL) of cancer patients (pts), thus affecting multiple aspects of daily simple physical activities. [1][2][3] In the last decade, several small-molecule tyrosine kinase inhibitors (TKIs), such as sunitinib (SU), sorafenib (SO) or pazopanib (PZ), have been developed as angiogenesis inhibitors and have demonstrated their efficacy in a variety of solid tumors. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] Presently, SO is approved for pts with advanced renal cell cancer (RCC) and hepatocellular cancer (HCC), SU is approved for treatment of advanced RCC as well as imatinib-resistant gastrointestinal stromal tumor (GIST), while PZ is approved for advanced RCC and soft tissue sarcoma (STS).However, the use of VEGFR TKIs is limited by the occurrence of different side effects, such as fatigue. TKI-induced

Fatigue with vascular endothelial growth factor receptor tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors in patients with renal cell carcinoma (RCC) and other malignancies: A meta-analysis of randomized clinical trials

“…Additionally, their meta-analysis included single-arm studies. Another recent meta-analysis evaluated the RR of fatigue in patients receiving only sunitinib, pazopanib and sorafenib [4]. However, even this meta-analysis included trials of combinations with chemotherapy, and does not isolate fatigue when using any VEGFR TKI as a single agent.…”

“…In addition to other adverse effects, these agents have been commonly reported to cause fatigue [1][2][3][4]. Fatigue is a subjective sense of tiredness related to cancer treatment, not in proportion to recent activity, which interferes with physical, emotional, and/or cognitive functioning [5,6].…”

Risk of fatigue in patients with solid tumors treated with everolimus, temsirolimus or ridaforolimus: a comparative meta-analysis

“…In patients with RCC, in particular, pazopanib showed the lower incidence and RR of all-and high-grade fatigue. The differences were significant for sunitinib versus sorafenib (p < 0.001), sunitinib versus pazopanib (p < 0.001) and sorafenib versus pazopanib (p < 0.001) [28].…”

Nebenwirkungsmanagement von Tyrosinkinaseinhibitoren in der Urologie

“…Patienten mit metastasiertem Nierenzellkarzinom haben unter Pazopanib seltener Fatiguebeschwerden als unter Sunitinib oder Sorafenib [15].…”