title: 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 = 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.
authors.affiliation: Department of Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Ancona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Santoni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Conti
authors.forename: Ugo
authors.initials: U
authors.lastname: De Giorgi
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacovelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Pantano
authors.forename: Luciano
authors.initials: L
authors.lastname: Burattini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Muzzonigro
authors.forename: Rossana
authors.initials: R
authors.lastname: Berardi
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D002292:Carcinoma, Renal Cell / Q000188:drug therapy; D002986:Clinical Trials as Topic; D003967:Diarrhea / Q000139:chemically induced; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D041981:Gastrointestinal Tract / Q000187:drug effects*; D006801:Humans; D015994:Incidence; D007191:Indazoles; D007211:Indoles / Q000009:adverse effects*; D008113:Liver Neoplasms / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000009:adverse effects*; D011743:Pyrimidines / Q000009:adverse effects*; D011758:Pyrroles / Q000009:adverse effects*; D000077157:Sorafenib; D013449:Sulfonamides / Q000009:adverse effects*; D000077210:Sunitinib; D014839:Vomiting / Q000139:chemically induced
chemical_list: D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D009536:Niacinamide; C516667:pazopanib; D000077157:Sorafenib; D000077210:Sunitinib
keywords: cancer; gastrointestinal adverse events; meta-analysis; renal cell carcinoma; tyrosine kinase inhibitors