New biomarkers of sunitinib efficacy in metastatic renal cell carcinoma

Abstract

Background: Hypertension, hypothyroidism, thrombocytopenia and neutropenia are frequent side effects of sunitinib. Preliminary studies suggested that drug- related toxicity may correlate with a better prognosis. Material and methods: We retrospectively analyzed clinical records of patients ( pts) affected by metastatic renal cell carcinoma (mRCC) treated with sunitinib as first-line therapy. We evaluated the following toxicities: hypertension (blood pressure > 140/90 mmHg or blood pressure requiring intensification of a pre-existing anti-hypertensive medication), hypothyroidism (requiring hormone replacement therapy, with or without symptoms), thrombocytopenia ( platelet count <100.000) and neutropenia (neutrophils <500). Overall survival (OS) and progression free survival (PFS) were calculated until 24 months of follow up. OS and PFS in patients who developed and who did not develop a drug- related toxicity were compared using T-test and X2 or Fisher exact test. Results: Thirty pts (19 males), median age 70.4 years, were evaluated; 20 pts (66%) had pre-existing controlled hypertension and four pts (13,3%) pre-existing hypothyroidism (in therapy). Complete blood count was normal in all the pts before starting the treatment. Twenty-two pts (73,3%) experienced at least one toxicity: 14 pts (46.6%) developed hypothyroidism, 8 pts (26,6%) hypertension that required medical therapy, 13 pts (43%) thrombocytopenia and 2 pts (6.6%) neutropenia. We found that median OS and median PFS of pts who developed hypothyroidism was 21.6 vs 12.8 months (p = 0.04), and 13.7 vs 8 months (p = 0.064), respectively. Median OS and median PFS of pts who developed hypertension was 22.3 vs 14.7 months (p = 0.028), and 16.5 vs 8.8 months (p = 0.023), respectively. No significant difference in OS and PFS was found in pts who developed only thrombocytopenia or neutropenia ( probably due to the small number of patients included). Median OS and median PFS were significantly longer in patients who developed at least one toxicity vs patients who did not: 20,5 vs 8 months (p = 0.0001) and 12.7 vs 6,7 months (p = 0.088), respectively. Conclusions: In patients with mRCC treated with sunitinib, the development of drug-related toxicity, in particular hypertension and hypothiroidism appeared associated with a longer OS and PFS. Other studies are necessary to confirm our preliminary findings.