Treatment-related adverse effects with pazopanib, sorafenib and sunitinib in patients with advanced soft tissue sarcoma: a pooled analysis

Abstract

ObjectiveResearch efforts have investigated therapies targeting tyrosine kinase signaling pathways. We performed a pooled analysis to determine the frequency of severe adverse effects in patients with soft tissue sarcoma treated with pazopanib, sorafenib and sunitinib.Materials and methodsWe performed a comprehensive search of PubMed, Web of Science, Ovid, the Cochrane Library and Embase databases from the drugs’ inception to May 2017 to identify clinical trials. All-grade and severe adverse events (AEs; grade≥3) were analyzed.ResultsA total of 10 trials published between 2009 and 2016, including 843 patients, were eligible for analysis. We included 424 patients (three studies) who received pazopanib 800 mg daily, 353 patients (five studies) who received sorafenib 400 mg twice daily and 66 patients (two studies) who received sunitinib 37.5 mg daily. The incidence of AEs is different among the three VEGFR-tyrosine kinase inhibitors (TKIs). Pazopanib showed higher incidence of all-grade nausea, diarrhea and hypertension compared with sorafenib and sunitinib. However, patients in the sorafenib group experienced a significantly higher frequency of all-grade rash (26.1%), hand–foot syndrome (33.4%) and mucositis (38.5%). The difference was highly significant for sorafenib vs. pazopanib in the incidence of all-grade rash (odds ratio [OR] 1.649, 95% CI 1.086–2.505, P=0.023), hand–foot syndrome (OR 3.096, 95% CI 1.271–7.544, P=0.009) and mucositis (OR 4.562, 95% CI 2.132–9.609, P<0.001). Moreover, the frequency of grade ≥3 mucositis was significantly higher in the sunitinib group compared with the pazopanib or sorafenib group (7.6% vs. 1.3%, OR 6.448, 95% CI 1.499–27.731, P=0.013).ConclusionStatistically significant differences in certain common adverse effects, such as all-grade and severe AEs, were detected among pazopanib, sorafenib and sunitinib in the current study. Early and prompt management is critically needed to avoid unnecessary dose reductions and treatment-related discontinuations.

Oral Intake of Royal Jelly Has Protective Effects Against Tyrosine Kinase Inhibitor-Induced Toxicity in Patients with Renal Cell Carcinoma: A Randomized, Double-Blinded, Placebo-Controlled Trial

“…In this study, we investigated the preventive effects of prophylactic RJ consumption on AEs associated with TKI-induced toxicities because the appropriate management of these AEs is critical for maintaining quality of life in RCC patients treated with TKIs. Various harmful symptoms and abnormal observations are known as adverse events of TKIs [12,14,15,16,17,18]. Among these chemotherapy-induced symptoms, such as oral mucositis, anorexia, digestive symptoms, fatigue, and damage of the kidneys and liver, few have been shown to be suppressed by RJ administration in animal experiments and clinical trials [27,28,29,30,31,32,33,34,37].…”

“…On the other hand, axitinib and sorafenib are also used in some patients with metastatic RCC [12,13]. Typical AEs linked to these TKIs include various symptoms such as oral mucositis, hand–foot syndrome, hypertension, fatigue, and gastrointestinal events [14,15,16,17,18]. In addition, functional disorders of the kidneys, liver, and thyroid are often associated with TKIs [14,15,17].…”

Effects of VEGFR1+ hematopoietic progenitor cells on pre-metastatic niche formation and in vivo metastasis of breast cancer cells

“…For example, transforming growth factor (TGF)-β1 is known as a tumor inhibitor during the early stage of different cancers, whereas it functions as a tumor promoter (promoting tumor invasion and metastasis) during the later stages (Heldin et al 2017 ). Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) play critical roles in angiogenesis during tumor growth and metastasis (Que et al 2018 ; Shay et al 2015 ). MMPs, known as physiologic scissors, are involved in extracellular matrix (ECM) degradation and tissue remodeling (Lee et al 2018 ).…”

Pazopanib-induced fatal heart failure in a patient with unresectable soft tissue sarcoma and review of literature

“…25 Que et al conducted a pooled analysis with 10 trials published between 2009 and 2016, including 843 patients, and examined treatment-related adverse effects with pazopanib, sorafenib, and sunitinib in patients with advanced STS, and as a result, they did not report any cardiac severe dysfunction. 26 Conversely, Hall et al evaluated 159 patients receiving TKIs including pazopanib for the treatment of advanced RCC and showed that the cardiotoxicity related to all study drugs when hypertension was excluded varied from occurrence of asymptomatic drops in LVEF to severe HF was 33%, and the rate of decreased LVEF (grades 2-4) related only to pazopanib was 7%, which are higher than the general rates reported in the literature. Also, they concluded that in the previous studies the incidence of asymptomatic cardiovascular toxicity has not been reported and therefore, the frequency and severity of cardiovascular toxicity in their cohort were high.…”