BACKGROUND: Sorafenib is a vascular endothelial growth factor receptor tyrosine-kinase inhibitor currently used in several malignancies. While not a traditional cytotoxic chemotherapeutic agent, hematological toxicities have been reported with this drug but the incidence and risk have not been formerly assessed. We performed a meta-analysis to determine the incidence and risk of hematologic toxicities associated with sorafenib use. METHODS: The databases of Medline were searched for articles from 1966 to May 2010. Abstracts presented at the American Society of Clinical Oncology meetings were also searched. Eligible studies include randomized trials with sorafenib, and adequate safety data profile reporting anemia, neutropenia, lymphopenia or thrombocytopenia. Statistical analyses were conducted to calculate the summary incidence, RR and 95% confidence intervals (CI). RESULTS: A total of 3221 patients were included. The incidences of sorafenib-associated all-grade anemia, neutropenia, thrombocytopenia and lymphopenia were 43.9%, 18.0%, 25.3% and 34.1%, respectively. The incidences of high-grade events were 2.0%, 5.1%, 4.0% and 13.1%, respectively. Sorafenib was associated with a decreased risk of high-grade anemia (RR=0.62; 95% CI, 0.39-0.98), an increased risk of all-grade (RR=1.69; 95% CI, 1.33-2.17) and high-grade (RR=1.61; 95% CI, 1.02-2.57) neutropenia, all-grade (RR=2.56; 95% CI, 1.37-4.80) and high-grade (RR=3.63; 95% CI, 1.98-6.66) thrombocytopenia, and high-grade lymphopenia (RR=1.84; 95% CI, 1.22-2.78). Stratified analysis by the presence or not of concomitant chemotherapy demonstrated similar risks. CONCLUSIONS: Independent of cytotoxic chemotherapy, sorafenib has significant hematologic toxicities, with a decreased risk of anemia and increased risk of neutropenia, thrombocytopenia and lymphopenia.
BACKGROUND:Sorafenib is a vascular endothelial growth factor receptor tyrosine-kinase inhibitor currently used in several malignancies. While not a traditional cytotoxic chemotherapeutic agent, hematological toxicities have been reported with this drug but the incidence and risk have not been formerly assessed. We performed a meta-analysis to determine the incidence and risk of hematologic toxicities associated with sorafenib use. METHODS: The databases of Medline were searched for articles from 1966 to May 2010. Abstracts presented at the American Society of Clinical Oncology meetings were also searched. Eligible studies include randomized trials with sorafenib, and adequate safety data profile reporting anemia, neutropenia, lymphopenia or thrombocytopenia. Statistical analyses were conducted to calculate the summary incidence, RR and 95% confidence intervals (CI). RESULTS: A total of 3221 patients were included. The incidences of sorafenib-associated all-grade anemia, neutropenia, thrombocytopenia and lymphopenia were 43.9%, 18.0%, 25.3% and 34.1%, respectively. The incidences of high-grade events were 2.0%, 5.1%, 4.0% and 13.1%, respectively. Sorafenib was associated with a decreased risk of high-grade anemia (RR=0.62; 95% CI, 0.39-0.98), an increased risk of all-grade (RR=1.69; 95% CI, 1.33-2.17) and high-grade (RR=1.61; 95% CI, 1.02-2.57) neutropenia, all-grade (RR=2.56; 95% CI, 1.37-4.80) and high-grade (RR=3.63; 95% CI, 1.98-6.66) thrombocytopenia, and high-grade lymphopenia (RR=1.84; 95% CI, 1.22-2.78). Stratified analysis by the presence or not of concomitant chemotherapy demonstrated similar risks. CONCLUSIONS: Independent of cytotoxic chemotherapy, sorafenib has significant hematologic toxicities, with a decreased risk of anemia and increased risk of neutropenia, thrombocytopenia and lymphopenia.
Authors: Brian I Carr; Rosalba D'Alessandro; Maria G Refolo; Palma A Iacovazzi; Catia Lippolis; Caterina Messa; Aldo Cavallini; Mario Correale; Antonio Di Carlo Journal: J Cell Physiol Date: 2013-06 Impact factor: 6.384
Authors: Jahan S Khalili; Shujuan Liu; Tania G Rodríguez-Cruz; Mayra Whittington; Seth Wardell; Chengwen Liu; Minying Zhang; Zachary A Cooper; Dennie T Frederick; Yufeng Li; Min Zhang; Richard W Joseph; Chantale Bernatchez; Suhendan Ekmekcioglu; Elizabeth Grimm; Laszlo G Radvanyi; Richard E Davis; Michael A Davies; Jennifer A Wargo; Patrick Hwu; Gregory Lizée Journal: Clin Cancer Res Date: 2012-07-31 Impact factor: 12.531
Authors: D Cunningham; R P W Wong; G D'Haens; J-Y Douillard; J Robertson; A M Stone; E Van Cutsem Journal: Br J Cancer Date: 2013-01-08 Impact factor: 7.640