-
Journal of the American Academy of... Nov 2013Pruritus has been anecdotally described in association with targeted cancer therapies. The risk of pruritus has not been systematically ascertained. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pruritus has been anecdotally described in association with targeted cancer therapies. The risk of pruritus has not been systematically ascertained.
OBJECTIVE
A systematic review and meta-analysis of the literature was conducted for axitinib, cetuximab, dasatinib, erlotinib, everolimus, gefitinib, imatinib, ipilimumab, lapatinib, nilotinib, panitumumab, pazopanib, rituximab, sorafenib, temsirolimus, tositumomab, vandetanib, and vemurafenib.
METHODS
Databases from PubMed, Web of Science (January 1998 through July 2012), and American Society of Clinical Oncology abstracts (2004 through 2012) were searched. Incidence and relative risk of pruritus were calculated using random- or fixed-effects model.
RESULTS
The incidences of all-grade and high-grade pruritus were 17.4% (95% confidence interval 16.0%-19.0%) and 1.4% (95% confidence interval 1.2%-1.6%), respectively. There was an increased risk of all-grade pruritus (relative risk 2.90 [95% confidence interval 1.76-4.77, P < .001]) and variation among different drugs (P < .001).
LIMITATIONS
The reporting of pruritus may vary, resulting from concomitant medications, comorbidities, and underlying malignancies. We found a higher incidence of pruritus in patients with solid tumors, concordant with those targeted therapies with the highest pruritus incidences.
CONCLUSION
There is a significant risk of developing pruritus in patients receiving targeted therapies. To prevent suboptimal dosing and decreased quality of life, patients should be counseled and treated against this untoward symptom.
Topics: Drug Eruptions; Humans; Molecular Targeted Therapy; Neoplasms; Pruritus
PubMed: 23981682
DOI: 10.1016/j.jaad.2013.06.038 -
BMC Cancer Aug 2013Current guidelines recommend anthracycline-based chemotherapy primarily with doxorubicin either as monotherapy or in combination with ifosfamide as the first-line... (Review)
Review
BACKGROUND
Current guidelines recommend anthracycline-based chemotherapy primarily with doxorubicin either as monotherapy or in combination with ifosfamide as the first-line treatment for most advanced STS subtypes. Therapeutic options after failure of doxorubicin and/or ifosfamide are limited. This study aimed to comprehensively review available data on the activity and safety of interventions in second- or later-line treatment of advanced STS.
METHODS
Electronic literature databases (Embase®, MEDLINE®, MEDLINE® In-Process, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews) were searched from 1980 to 01 March 2012 to identify randomised controlled trials (RCTs) and non-randomised studies (both prospective and retrospective) evaluating pharmacological interventions in patients with advanced STS pre-treated with anthracycline- and/or ifosfamide-based therapy.
RESULTS
The review identified six RCTs (one phase III and five phase II trials) and 94 non-randomised studies. Based on the primary trial endpoints, RCTs demonstrated favourable efficacy for pazopanib over placebo (PFS: 4.6 months vs. 1.6 months), gemcitabine plus dacarbazine over dacarbazine monotherapy (3-month PFS rate: 54.2% vs. 35.2%), and trabectedin 3-weekly schedule over weekly schedule (TTP: 3.7 months vs. 2.3 months. The non-randomised studies demonstrated heterogeneity in efficacy and safety results.
CONCLUSIONS
Across the RCTs, pazopanib over placebo, gemcitabine-dacarbazine over dacarbazine, and trabectedin 3-weekly over weekly regimen clearly demonstrated a PFS advantage in the second- and later-line treatment of advanced STS. With only one phase III trial in this setting, there is a clear need for additional comparative trials to better understand the risk: benefit ratios of available agents and combinations.
Topics: Antineoplastic Agents; Dacarbazine; Deoxycytidine; Dioxoles; Humans; Indazoles; Pyrimidines; Randomized Controlled Trials as Topic; Sarcoma; Sulfonamides; Tetrahydroisoquinolines; Trabectedin; Treatment Failure; Gemcitabine
PubMed: 23937858
DOI: 10.1186/1471-2407-13-385 -
British Journal of Clinical Pharmacology Sep 2013To investigate the overall incidence and risk of hypertension in cancer patients who receive axitinib and compare the differences in incidences between axitinib and the... (Meta-Analysis)
Meta-Analysis Review
AIMS
To investigate the overall incidence and risk of hypertension in cancer patients who receive axitinib and compare the differences in incidences between axitinib and the other four approved vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs).
METHODS
Several databases were searched, including Pubmed, Embase and Cochrane databases. Eligible studies were phase II and III prospective clinical trials of patients with cancer assigned axitinib at a starting dose of 5 mg orally twice daily with data on hypertension available. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed or random effects models depending on the heterogeneity of the included trials.
RESULTS
A total of 1908 patients from 10 clinical trials were included. The overall incidences of all grade and high grade hypertension in cancer patients were 40.1% (95% CI 30.9, 50.2%) and 13.1% (95% CI 6.7, 24%). The use of axitinib was associated with significantly increased risk of all grade (RR 3.00, 95% CI 1.29, 6.97, P = 0.011) and high grade hypertension (RR 1.71, 95% CI 1.21, 2.43, P = 0.003). The risk of axitinib associated all grade and high grade hypertension in renal cell carcinoma (RCC) was significantly higher than that in non-RCC. Additionally, the risk of hypertension with axitinib was substantially higher than other approved VEGFR-TKIs, while the risk of all grade hypertension with axitinib was similar to pazopanib (RR 1.05; 95% CI 0.95-, 1.17, P = 0.34).
CONCLUSIONS
While sharing a similar spectrum of target receptors with other VEGFR-TKIs, axitinib is associated with an unexpectedly high risk of developing hypertension. Close monitoring and appropriate management for hypertension are recommended during the treatment.
Topics: Antineoplastic Agents; Axitinib; Clinical Trials as Topic; Humans; Hypertension; Imidazoles; Incidence; Indazoles; Molecular Targeted Therapy; Neoplasms; Protein Kinase Inhibitors; Receptors, Vascular Endothelial Growth Factor; Risk
PubMed: 23617405
DOI: 10.1111/bcp.12149