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Toxicities related to survival in RCC patients receiving sunitinib, sorafenib
Di Fiore F. Br J Cancer. 2011;105:1811-1813.
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Patients with renal cell carcinoma who were treated with sunitinib and/or sorafenib and experienced severe toxicity had a better survival, according to researchers from Rouen University Hospital in France.
“Until now, analysis of tyrosine kinase inhibitor-induced toxicities has been mainly descriptive, using a global evaluation and counting of adverse events occurring in patients selected for randomized studies,” the researchers wrote. “On the basis of this approach, the impact of tyrosine kinase inhibitor-related toxicities on outcome has not yet been definitively established.”
The study included all consecutive patients with renal cell carcinoma (RCC) who were treated with sunitinib (Sutent, Pfizer) and/or sorafenib (Nexavar, Bayer) from June 2006 to June 2008. The patients were classified according to the Memorial Sloan-Kettering Cancer Center (MSKCC) risk score. The researchers collected information on clinical characteristics, toxicities and comorbidities at time of treatment initiation, and the Charlson comorbidity index was calculated.
One cycle of sunitinib included 4 weeks of 50 mg/day, followed by a 2-week break. One cycle of sorafenib included 4 consecutive weeks of 400 mg twice daily without discontinuation. Patient follow-up was performed at day 1, 14 and 28 of the first treatment cycle, and at least monthly during the treatment exposure.
There were 38 patients evaluated: 14 received sunitinib, nine received sorafenib and 15 received both drugs. Toxicities were observed in 88.7% of the patients: digestive in 73.6%, cardiac in 64.1%, dermatologic in 52.3% and asthenia in 52.3%. Grade-3 or -4 cardiac toxicities were more frequent in those who received sunitinib, in which grade-3 or -4 dermatologic effects were observed in those who received sorafenib. Comorbidity index score was an independent predictive factor of toxicities (P=.02).
The 2-year survival rate was 78% in patients with low and intermediate MSKCC risk score vs. 36% in those with a poor risk score. The median OS was 36 months in patients with grade-3 or -4 toxicities vs. 12 months in patients without toxicities (P=.009). Patients who had a Charlson score of more than 7 has a median OS of 12 months vs. a median OS of 36 months for patients who had a Charlson score of less than 7.
“These findings suggested that clinical tyrosine kinase inhibitor-related side effects may be in relation with patient conditions and may also be a marker of drug efficacy,” the researchers wrote.
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There are a number of retrospective analyses about toxicity and outcome to VEGF-targeted therapy in RCC. Most of them have looked at an individual toxicity, such as hypertension, hand-foot syndrome, neutropenia, hypothyroidism or fatigue. These analyses have consistently found an association of toxicity with better outcome. However, the longer a patient is on therapy, the more likely they are to have significant toxicity. Unless the analyses consider time on therapy, they can be hard to interpret. This study didn’t account for time on therapy by performing, for instance, a landmark analysis. Further, it is hard to interpret if all toxicity is good or whether outcome is driven by a specific toxicity. Hypertension is probably the most studied of the toxicities, and in my opinion, there is a clear association between treatment-induced hypertension and clinical outcome. The important part is to understand the biology of this association and, thus, how we can use it to identify patients prior to therapy who will benefit from a specific treatment over an alternative.
Brian I. Rini, MD
HemOnc Today
Editorial Board member
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