Cytokine rise signals RCC progression

Dec 17 2012

By Joanna Lyford, Senior medwireNews Reporter

Progression of renal cell carcinoma (RCC) is frequently preceded by a rise in levels of proangiogenic cytokines, Italian researchers have found.

The discovery could pave the way for cytokines to be monitored as an early warning sign of disease progression as well as to guide treatment options, say Camillo Porta (San Matteo University Hospital Foundation, Pavia) and fellow researchers.

Porta and team studied 85 patients with advanced RCC being treated with sunitinib. On the first day of each treatment cycle the researchers measured circulating levels of three proangiogenic cytokines: basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and interleukin (IL)-6.

Analysis of the entire patient population found that cytokine titers did not change significantly between baseline and the time of disease progression, report Porta et al in Oncology.

However, analysis on a patient-by-patient basis revealed that a substantial number of individuals showed increases in the three cytokines - and in IL-6 and bFGF in particular - at the time of disease progression.

Specifically, 45.3%, 46.6%, and 37.3% of patients exhibited a more-than-50% increase in IL-6, bFGF, and HGF titers, respectively, while 37.3%, 44.0%, and 30.6% of patients, respectively, had a more-than-100% rise.

These increases typically occurred immediately before disease progression and were sustained thereafter, the authors note. Just 14 (18.6%) patients showed a simultaneous increase in all three cytokines, they add.

Interestingly, the percentage increase in bFGF was significantly correlated with the number of metastatic sites but not with other clinical variables such as progression-free survival. Also, bFGF levels rose ahead of disease progression irrespective of the benefit or otherwise of sunitinib therapy.

Porta et al hypothesize that the increase in circulating cytokines, particularly bFGF, before radiologic disease progression, "suggests a shift towards alternative proangiogenic pathways as a key mechanism of resistance to an anti-VEGF receptor pathway treatment."

They conclude: "Our data suggest that in a large percentage of advanced RCC patients, progression under sunitinib treatment is preceded by a significant increase in the production of IL-6, HGF (to a lesser extent), and especially bFGF…

"Therefore, other studies are needed to prospectively confirm our data on a larger patient population and to fully evaluate the way in which this information can be exploited in therapy."

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