Critical reviews in oncology/hematology
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Crit. Rev. Oncol. Hematol. · Jul 2015
ReviewMolecular targeted therapies in advanced or metastatic chordoma patients: facts and hypotheses.
Chordomas, derived from undifferentiated notochordal remnants, represent less than 4% of bone primary tumors. Despite surgery followed by radiotherapy, local and metastatic relapses are frequent. In case of locally advanced or metastatic chordomas, medical treatment is frequently discussed. ⋯ Other putative targets have also been described. Therefore, further clinical trials are expected, especially with these targets. Nevertheless, it seems essential, in those future studies, to consider the naturally slow course of the disease.
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Crit. Rev. Oncol. Hematol. · Jun 2015
ReviewTrabectedin: Supportive care strategies and safety profile.
Trabectedin is an approved antineoplastic agent for the treatment of adult patients with advanced soft tissue sarcomas or in combination with pegylated liposomal doxorubicin (PLD) in patients with relapsed platinum sensitive ovarian cancer. The mechanism of action is still not fully understood but many typical side effects seen with other chemotherapy drugs are less common, mild or unreported. ⋯ However, for most patients the appropriate use of supportive care strategies can reduce or overcome these side effects. We present a concise review of the safety data of trabectedin with the corresponding overview of the supportive care strategies.
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Crit. Rev. Oncol. Hematol. · May 2015
Review Meta AnalysisCongestive heart failure with vascular endothelial growth factor receptor tyrosine kinase inhibitors.
A systematic review and meta-analysis was conducted to determine the relative risk (RR) of congestive heart failure (CHF) associated with approved multi-targeted vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). Eligible studies included randomized trials comparing arms with and without an FDA-approved VEGFR TKI. Statistical analyses calculated the relative risk (RR) and 95% confidence intervals (CI). ⋯ High-grade CHF occurred in 17 of 1426 (1.19%) patients receiving VEGFR TKIs and 8 of 1232 (0.65%) patients in the non-TKI group. The RR of all grade and high-grade CHF for the TKI vs. no TKI arms was 2.69 (p<0.001; 95% CI: 1.86 to 3.87) and 1.65 (p=0.227, 95% CI: 0.73 to 3.70), respectively. The RR of relatively specific TKIs (axitinib) was similar to relatively non-specific TKIs (sunitinib, sorafenib, vandetanib, pazopanib).
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Crit. Rev. Oncol. Hematol. · Apr 2015
Review Meta AnalysisPancreatitis with vascular endothelial growth factor receptor tyrosine kinase inhibitors.
A trial-level meta-analysis was conducted to determine the relative risk (RR) of pancreatitis associated with multi-targeted vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). Eligible studies included randomized phase 2 and 3 trials comparing arms with and without an FDA-approved VEGFR TKI (sunitinib, sorafenib, pazopanib, axitinib, vandetanib, cabozantinib, ponatinib, regorafenib). Statistical analyses calculated the RR and 95% confidence intervals (CI). ⋯ The RR for all grade and high-grade pancreatitis for the TKI vs. no TKI- arms was 1.95 (p=0.042, 95% CI: 1.02 to 3.70) and 1.89 (p=0.069, 95% CI: 0.95 to 373), respectively. No differential impact of malignancy type or specific TKI agent was seen on RR of all grade of high grade pancreatitis. Better patient selection and monitoring may mitigate the risk of severe pancreatitis.
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Crit. Rev. Oncol. Hematol. · Mar 2015
Review Meta AnalysisHepatotoxicity with vascular endothelial growth factor receptor tyrosine kinase inhibitors: A meta-analysis of randomized clinical trials.
A meta-analysis of randomized controlled trials (RCT) was conducted to determine the relative risk (RR) of hepatotoxicity with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). Citations from PubMed/Medline, abstracts from major conferences, clinicaltrials.gov and package inserts were reviewed to include RCTs comparing arms with or without a VEGFR TKI. The RRs of all-grade ALT, AST, ALP and bilirubin elevation in 18,282 patients from 52 trials were 1.57 (95% CI 1.38-1.79, p<0.001), 1.57 (95% CI 1.36-1.81, p<0.001), 1.20 (95% CI 1.09-1.83, p<0.001) and 1.55 (95% CI 1.21-1.97, p<0.001) respectively, and high-grade elevations were 1.66 (95% CI 1.25-2.20, p=0.001), 1.61 (95% CI 1.21-2.14, p=0.001), 1.02 (95% CI 0.70-1.47, p=0.932) and 1.34 (95% CI 1.0-1.81, p=0.054) respectively compared to those in the non-TKI group. The incidence of hepatic failure with VEGFR TKIs was 0.8%.