Organ-specific and tumor-size-dependent responses to sunitinib in clear cell renal cell carcinoma

Abstract

BackgroundTyrosine kinase inhibitors (TKIs) have been used as standard therapy for patients with advanced renal cell carcinoma (RCC). However, information on factors predicting response to treatment with TKIs is lacking. This study aimed to assess the association between initial tumor size, involved organs, pre-treatment C-reactive protein (CRP) levels, and reduction in tumor size in patients with clear cell RCC (CCRCC) treated with sunitinib.MethodsPatients with advanced CCRCC with target lesions with a maximum diameter ≥ 10 mm treated with sunitinib were evaluated. The tumor diameter representing the best overall response was designated as the post-treatment tumor diameter.ResultsA total of 179 lesions in 38 patients were analyzed. Organ-specific analysis demonstrated that pre-treatment diameter of lung metastatic lesions had a moderate inverse association with percent reduction in post-treatment tumor diameter (R = 0.341). Lung lesions showed significantly greater percent reductions in diameter than liver and kidney lesions (P = 0.007 and 0.002, respectively). Furthermore, based on a CRP cut-off level of 2.0 mg/dl, mean tumor size reduction was significantly greater in patients with low CRP levels than in patients with high CRP levels in lesions with diameters < 20 mm (P = 0.002). CRP level had no effect on mean size reduction in lesions with a diameter ≥ 20 mm.ConclusionsPatients with CCRCC with smaller lung metastatic lesions and lower CRP levels may achieve greater percent reductions in tumor size with sunitinib therapy than patients with extra-pulmonary lesions, large lung lesions, and/or higher CRP levels.

Sunitinib enhances the antitumor responses of agonistic CD40-antibody by reducing MDSCs and synergistically improving endothelial activation and T-cell recruitment

“…Importantly, all mice treated with anti-CD40 mAb in combination with sunitinib lived beyond day 22, as compared to 0/8 control mice, 3/7 mice treated with anti-CD40 mAb alone and 4/8 mice treated with sunitinib alone (Figure 5B-5F). Continued treatment with sunitinib as a monotherapy inhibited tumor growth only when the tumor size at the start of the treatment was smaller than 20 mm 3 , but was not effective in larger tumors (Figure 5E), which is in agreement with previous reports [29–31]. These results show that continued treatment with anti-CD40 mAb in combination with sunitinib is superior to monotherapies and further enhances the survival of mice bearing B16.F10 melanomas.…”

The Role of C-Reactive Protein in Kidney, Bladder, and Prostate Cancers

“…It is important to note that a 2014 retrospective study by Tsuchiya et al which focused on sunitinib response found that high CRP was correlated with superior tumor size reduction in metastases only in tumors that were <20mm before treatment. In larger tumors, CRP level was not found to have any effect on mean size reduction (36). These findings could suggest that the utility of CRP becomes more limited as disease severity increases, although further research is needed.…”

Tumor shrinkage patterns of nivolumab monotherapy in metastatic renal cell carcinoma

“…In TKI treatment, a reduction in tumor size >10%, calculated as the sum of the longest diameter of the target lesions, was significantly associated with both time to treatment failure and overall survival (OS), suggesting that size reduction of target lesions may predict the outcome of treatment with TKIs 15 . We also demonstrated that a smaller initial tumor size predicted a good response to TKIs, and that lung lesions demonstrated significantly greater percent reductions in diameter than liver and kidney lesions 16,17 . In ICI treatment, we found that the patterns of tumor shrinkage and size reduction might be different from those in TKI treatment.…”

“…In addition, multivariate linear regression analysis revealed that only the initial tumor size was independently associated with the individual size reduction rate ( p < 0.001) 16 . We also investigated the associations between pretreatment tumor size and TSR of individual target lesion in each of four organs (lungs, liver, lymph nodes, and kidneys) 17 . The percent changes in target lesion size differed significantly between the four individual organs and the target lesions in the lung showed the greatest change in size, which was significantly greater than those in the liver and kidney 17 .…”

“…We also investigated the associations between pretreatment tumor size and TSR of individual target lesion in each of four organs (lungs, liver, lymph nodes, and kidneys) 17 . The percent changes in target lesion size differed significantly between the four individual organs and the target lesions in the lung showed the greatest change in size, which was significantly greater than those in the liver and kidney 17 . However, our study suggested that these tumor shrinkage patterns, which include the pretreatment tumor size and the target organs, might be completely different in ICI treatment.…”