NEW YORK (Reuters Health) Aug 08 - The cancer drug sunitinib (Sutent; Pfizer) nearly doubles patients' relative risk of new-onset congestive heart failure (CHF) and triples their risk of high-grade CHF, a new meta-analysis shows.
With clinical use of sunitinib "expected to expand greatly, I think this is something to be concerned about in several situations," said Dr. Toni K. Choueiri, from Dana-Farber Cancer Institute, Boston, in an interview with Reuters Health.
"I think it is reasonable to evaluate the cardiac function of patients before sunitinib," he said, "especially older patients and those with a history of heart problems. It doesn't mean I won't give sunitinib to these patients; it means I will monitor them and counsel them about signs of CHF because a lot of times it can present as vague symptoms, or I might use an alternative drug."
Sunitinib is approved for patients with metastatic renal cell carcinoma (RCC) and imatinib-resistant GI stromal tumor (GIST). It's currently being investigated in more than 30 tumor types in more than 300 clinical trials, Dr. Choueiri and colleagues noted in a paper published online August 1st in the Journal of Clinical Oncology.
CHF has been reported sporadically in several sunitinib trials but the true risk associated with its use remains undefined. For their meta-analysis, Dr. Choueiri and colleagues identified 16 trials involving 6,935 patients with RCC or non-RCC tumors.
In sunitinib-treated patients, the overall rates of any CHF and high-grade CHF were 4.1% and 1.5%, respectively, the investigators report.
The relative risks of any CHF and high-grade CHF with sunitinib compared with placebo were statistically significant, at 1.81 and 3.30, respectively.
It's not clear yet whether CHF in sunitinib-treated patients is dose-dependent or reversible. There's some evidence that a decline in left ventricular ejection fracture with sunitinib may be reversible, the investigators note.
Sunitinib is a small-molecule tyrosine kinase inhibitor that blocks the intracellular domain of the vascular endothelial growth factor (VEGF) receptor. The VEGF pathway is critical in maintaining functional cardiac myocardium, the authors point out.
There's "emerging data" that members of this drug class may carry increased risk of cardiac toxicity, they say. For instance, a recent meta-analysis of the anti-VEGF antibody bevacizumab found it more than tripled the risk of CHF in patients with breast cancer.
Sunitinib also increases the risk of hypertension, in line with other VEGF inhibitors, such as sorafenib and bevacizumab. As hypertension is a well known risk factor for CHF, it's possible that sunitinib use increased CHF through this mechanism, the investigators note.
Summing up, Dr. Choueiri and colleagues say clinicians need to be aware of the risk of CHF with sunitinib treatment to provide early intervention and balance therapeutic benefit with this potentially life-threatening adverse effect.
SOURCE: http://bit.ly/rcE98R
J Clin Oncol 2011.
With clinical use of sunitinib "expected to expand greatly, I think this is something to be concerned about in several situations," said Dr. Toni K. Choueiri, from Dana-Farber Cancer Institute, Boston, in an interview with Reuters Health.
"I think it is reasonable to evaluate the cardiac function of patients before sunitinib," he said, "especially older patients and those with a history of heart problems. It doesn't mean I won't give sunitinib to these patients; it means I will monitor them and counsel them about signs of CHF because a lot of times it can present as vague symptoms, or I might use an alternative drug."
Sunitinib is approved for patients with metastatic renal cell carcinoma (RCC) and imatinib-resistant GI stromal tumor (GIST). It's currently being investigated in more than 30 tumor types in more than 300 clinical trials, Dr. Choueiri and colleagues noted in a paper published online August 1st in the Journal of Clinical Oncology.
CHF has been reported sporadically in several sunitinib trials but the true risk associated with its use remains undefined. For their meta-analysis, Dr. Choueiri and colleagues identified 16 trials involving 6,935 patients with RCC or non-RCC tumors.
In sunitinib-treated patients, the overall rates of any CHF and high-grade CHF were 4.1% and 1.5%, respectively, the investigators report.
The relative risks of any CHF and high-grade CHF with sunitinib compared with placebo were statistically significant, at 1.81 and 3.30, respectively.
It's not clear yet whether CHF in sunitinib-treated patients is dose-dependent or reversible. There's some evidence that a decline in left ventricular ejection fracture with sunitinib may be reversible, the investigators note.
Sunitinib is a small-molecule tyrosine kinase inhibitor that blocks the intracellular domain of the vascular endothelial growth factor (VEGF) receptor. The VEGF pathway is critical in maintaining functional cardiac myocardium, the authors point out.
There's "emerging data" that members of this drug class may carry increased risk of cardiac toxicity, they say. For instance, a recent meta-analysis of the anti-VEGF antibody bevacizumab found it more than tripled the risk of CHF in patients with breast cancer.
Sunitinib also increases the risk of hypertension, in line with other VEGF inhibitors, such as sorafenib and bevacizumab. As hypertension is a well known risk factor for CHF, it's possible that sunitinib use increased CHF through this mechanism, the investigators note.
Summing up, Dr. Choueiri and colleagues say clinicians need to be aware of the risk of CHF with sunitinib treatment to provide early intervention and balance therapeutic benefit with this potentially life-threatening adverse effect.
SOURCE: http://bit.ly/rcE98R
J Clin Oncol 2011.
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου