NEW YORK (Reuters Health) Apr 07 - Sunitinib shows substantial activity in most patients with metastatic clear-cell renal carcinoma, Greek researchers report in a March 12th on-line paper in BMC Cancer. As yet, however, there are no clear indictors of which patients will gain benefit.
Dr. Konstantinos T. Papazisis told Reuters Health, "We report favorable outcomes and a good safety profile, similar to what has been observed in the pivotal trials. We also showed that shrinking the tumor doesn't really matter as long as we are able to stop it growing; patients with disease stabilization or disease remission have a similar overall survival."
Dr. Papazisis, of Theagenion Cancer Hospital, Thessaloniki, and colleagues report on treatment responses in 39 patients, 30 of whom obtained clinical benefit. Median progression-free survival was almost 9 months and median overall survival was more than 16 months.
In investigating possible indicators of response, the researchers found that patients with clinical benefit had significantly lower plasma VEGF increases compared to those with progression after 2 cycles of treatment. However, in patients with initial clinical benefit, subsequent progression did not lead to an increase in plasma VEGF.
Because sunitinib does not benefit every patient, Dr. Papazisis said, "We are on a search for markers that would predict outcome early on in the course of treatment. This would save unnecessary treatment-related side effects and costs."
BMC Cancer. 2009 Mar 12;9:82. Related Articles, References for this PMC Article, Free in PMC, LinkOut
Sunitinib treatment for patients with clear-cell metastatic renal cell carcinoma: clinical outcomes and plasma angiogenesis markers.
Kontovinis LF, Papazisis KT, Touplikioti P, Andreadis C, Mouratidou D, Kortsaris AH.
3rd Department of Medical Oncology, Theagenion Cancer Hospital, Al Simeonidi str. 2, 54007, Thessaloniki, Greece. loukas.kontovinis@gmail.com
BACKGROUND: Sunitinib is a protein tyrosine kinase-inhibitor targeting VEGFR, c-kit and PDGFR. It has been approved for the treatment of metastatic renal-cell carcinoma and gastrointestinal stromal tumors. Although it has been shown to prolong disease-free and overall survival in renal-cell carcinoma patients, only 70% of the treated population receive a clinical benefit (CB) from the treatment. Markers that could predict clinical benefit to sunitinib would be an important aid in monitoring and following their treatment. We assessed the outcome and plasma proangiogenic factors in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib in our institution. METHODS: We have treated 42 patients with metastatic clear-cell renal carcinoma with sunitinib. Plasma concentrations of VEGF-A, sVEGFR2 and PDGF were determined by ELISA. RESULTS: At the time of analysis 39 patients were evaluable for response and 30 patients had obtained a clinical benefit (CB). Median progression-free survival was 268 days (8.93 months) and median overall survival was 487 days (16.23 months). Interestingly, disease stabilization or objective response resulted in comparable overall survival. Most treatment-related adverse events were of mild-to-moderate intensity with one treatment-related death. Plasma sVEGFR2 and PDGF levels had no predictive value. Fold-increase in plasma VEGF was significantly lower in patients that obtained a CB as compared to patients that progressed after two cycles of treatment. Plasma VEGF did not increase in patients with initial CB at the time of progression. CONCLUSION: Sunitinib showed substantial activity in mRCC. Disease stabilization or objective response resulted in comparable overall survival and both outcomes should be considered positive. Fold-increase in plasma VEGF predicts for CB and could be a candidate marker. Progression after initial CB is not associated with elevated plasma VEGF, implying a different mechanism of resistance.
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