Macrocytosis during sunitinib treatment predicts progression-free survival in patients with metastatic renal cell carcinoma

Abstract

Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, is a first-line treatment for metastatic renal cell carcinoma (mRCC) in patients in ‘low’ and ‘intermediate’ Memorial Sloan Kettering Cancer Center and Heng risk groups. Disruptions of hematopoiesis, such as anemia, neutropenia, and thrombocytopenia, are typically observed during sunitinib treatment. When it comes to RBC parameters, an increase in mean cell volume (MCV) tends to occur, meeting the criteria for macrocytosis in some patients (MCV > 100 fL). We examined changes in RBC parameters of 27 mRCC patients treated with sunitinib (initial dose of 50 mg/day, 6-week treatment: 4 weeks on, 2 weeks off) and correlated them with progression-free survival time (PFS). Patients who had macrocytosis after 3 treatment cycles had significantly longer PFS than those whose MCV stayed less than 100 fL (not reached vs. 11.2 months, p < 0.001). We also found a correlation between MCV values after the first and third treatment cycles and the risk of progression: HR of 0.9 (0.81–0.99) and 0.76 (0.65–0.90) per 1 fL increase in MCV, respectively. The mechanism of MCV elevation during sunitinib treatment has not yet been fully explained. One of the probable causes is sunitinib’s inhibitory influence on c-Kit kinase, as is the case with imatinib. For mRCC patients, this phenomenon could help predict PFS, but since our sample was small, further studies are essential.

Synergism between the tyrosine kinase inhibitor sunitinib and Anti-TNF antibody protects against lethal dengue infection

“…Mice with sunitinib treatment had similar levels of DENV2 RNA in the serum and liver but higher levels in the spleen (0.5-fold, * P < 0.05) relative to mice with vehicle-treatment (Figure 2B), indicating that sunitinib treatment had no effect on viral burden in the serum or liver and modestly enhanced DENV burden in the spleen. In humans, sunitinib treatment has been reported to reduce hematocrit and both WBC and platelet cell counts (Korkmaz et al, 2014; Kucharz et al, 2016; Zhu et al, 2011). Moreover, elevated TNF levels, hematocrit, and WBC count and thrombocytopenia are associated with Severe Dengue (Chuansumrit and Chaiyaratana, 2014; WHO, 2009).…”

An International Phase 2 Study of Pazopanib in Progressive and Metastatic Thyroglobulin Antibody Negative Radioactive Iodine Refractory Differentiated Thyroid Cancer

“…1C)which we also examined as a nonprospectively specified candidate predictive biomarker pf RECIST response. Other multikinase inhibitors have been previously shown to increase MCV, perhaps due to the effects of inhibition of c-Kit on hematopoietic stem cells (12)(13)(14), so the noted pazopanibassociated increase in MCV appears to reflect a ''class-effect.'' Unlike reports in renal cell carcinoma in the case of other MKIs (12)(13)(14), the extent of MCV elevation did not in this study correlate with early RECIST response in RAIR-DTC.…”

“…Other multikinase inhibitors have been previously shown to increase MCV, perhaps due to the effects of inhibition of c-Kit on hematopoietic stem cells (12)(13)(14), so the noted pazopanibassociated increase in MCV appears to reflect a ''class-effect.'' Unlike reports in renal cell carcinoma in the case of other MKIs (12)(13)(14), the extent of MCV elevation did not in this study correlate with early RECIST response in RAIR-DTC. These data, combined with Tg and somatic mutational data, add to the body of growing evidence arguing against any yet identified credible early predictive candidate biomarkers of response to MKIs in RAIR DTC (15,16).…”

A Case of Cobalamin Deficiency and Macrocytic Anemia Secondary to Sunitinib

“…Additionally, among 10 patients in the analysis who had laboratories 2-3 months after discontinuation of sunitinib, MCV decreased by a median of 9.7 pL ( p = 0.002) [2]. Notably, some studies suggest macrocytosis secondary to treatment with sunitinib could be a marker of progression-free survival in RCC, as has been found with other TKI-associated toxicities such as hypertension and abnormal thyroid function [3,6].…”

“…Elevations in mean corpuscular volume (MCV) are also common, and in previous reports have been shown to occur in at least of patients on sunitinib after a median of 3 cycles of treatment [2]. Associations between sunitinib and deficiencies of folate and cobalamin (or vitamin B12) are less well-described but have been shown in small case series [3-5]. The case below involves a patient who developed macrocytic anemia with deficiencies of cobalamin and folate and bolsters evidence that megaloblastic anemia can occur in a subset of patients treated with sunitinib.…”