Risk of gastrointestinal events with sorafenib, sunitinib and pazopanib in patients with solid tumors: A systematic review and meta‐analysis of clinical trials

Abstract

Gastrointestinal (GI) events have been described with sorafenib, sunitinib and pazopanib in cancer patients. We performed an up-to-date meta-analysis to determine the incidence and relative risk (RR) in patients with cancer treated with these agents. PubMed databases were searched for articles published till May 2013. Eligible studies were selected according to PRISMA statement. Summary incidence, RR, and 95% CIs were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. A total of 6,447 patients were available for the meta-analysis; 2,260 had renal cell carcinoma (RCC) and 4,187, 1,691 non-small cell lung cancers, 599 hepatocellular cancers, 1,066 breast cancers, 165 neuroendocrine tumors, 304 gastrointestinal stromal tumors and 362 soft tissue sarcomas. Diarrhea was the most common GI event. When stratified by tumor type (RCC vs. non-RCC), the difference among the incidences of GI events was significant for diarrhea (p < 0.001) and vomiting (p 5 0.006), that resulted higher in RCC patients. In RCC patients, sorafenib registered the lower incidence and RR of all grades GI events. The difference was statistically significant for sorafenib versus sunitinib-related all and high-grade events (p < 0.001) and for sorafenib versus pazopanib all grades GI events (p < 0.001) and high-grade anorexia (p < 0.001). Treatment with VEGFR TKIs sorafenib, sunitinib and pazopanib is associated with a significant increase in the risk of GI events in patients with cancer, and frequent clinical monitoring should be emphasized when managing these three and newer VEGFR TKIs.

Variability in bioavailability of small molecular tyrosine kinase inhibitors

“…Dyspepsia and related gastrointestinal disorders have been reported as adverse reactions following therapy with smTKIs [11,12,[150][151][152]. Treatment options are the use of antacids, histamine H2 receptor antagonists and proton pump inhibitors (PPIs) [149].…”

Malnutrition Predicts Clinical Outcome in Patients with Neuroendocrine Neoplasia

“…Based on our results, these procedures utilized for a proper diagnosis of malnutrition have a high sensitivity for the detection of malnutrition and can rather easily be integrated into clinical routine. Certainly, nutritional therapy should be initiated to improve a patient's clinical state and quality of life and condition the patient for further treatments such as surgery, chemotherapy or some of the newly approved molecular targeted therapies which frequently are associated with some degree of weight loss [71,72,73,74]. The assumed beneficial effect of therapeutic nutritional interventions should be monitored not only via body weight, because this may be misleading in cases such as oedema formation, but also via the afore-mentioned serum surrogate parameters such as the course of serum albumin levels (taking into account the multiple differential diagnoses in the interpretation of the results) and via BIA measurements, which will likely represent the specific body compositional changes most precisely.…”

Risk of Gastrointestinal Events During Vandetanib Therapy in Patients With Cancer: A Systematic Review and Meta-analysis of Clinical Trials

“…3 Several RCTs and meta-analyses demonstrated that diarrhea was the most common adverse reaction in EGFRTKIs. 39,40 This type of diarrhea is thought to be primarily secretory; however, the mechanism still remains controversial. 41,42 Diarrhea can cause discomfort, fatigue, sleep disturbance, and can affect social function.…”