Hematologic Toxicity in Patients Treated with Sunitinib for Advanced Thyroid Cancer

Gkountouvas, Anastasios; Kostoglou-Athanassiou, Ifigeneia; Veniou, Eirini; Repousis, Panagiotis; Ziras, Nikolaos; Kaldrimidis, Philippos

doi:10.1089/thy.2010.0028

Cited by 13 publications

(6 citation statements)

References 18 publications

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“…First, body growth rate was significantly lower in Group S+Su than in Group S, indicating that the drug did exert a biological effect. Second, and in accordance with previous clinical observations [26], [27], the administration of sunitinib to Nx animals resulted in a decrease in hematocrit, not unexpected considering the known influence of VEGF on hematopoiesis [28], [29] and the low renal expression of VEGF observed in this group. The lack of effect of Su on blood pressure or proteinuria was paralleled by an equally undetectable effect on the density of endothelial cells, either in glomeruli or peritubular capillaries, at odds with the well-known anti-angiogenic action of the drug.…”

Section: Discussionsupporting

confidence: 89%

Chronic VEGF Blockade Worsens Glomerular Injury in the Remnant Kidney Model

et al. 2012

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VEGF inhibition can promote renal vascular and parenchymal injury, causing proteinuria, hypertension and thrombotic microangiopathy. The mechanisms underlying these side effects are unclear. We investigated the renal effects of the administration, during 45 days, of sunitinib (Su), a VEGF receptor inhibitor, to rats with 5/6 renal ablation (Nx). Adult male Munich-Wistar rats were distributed among groups S+V, sham-operated rats receiving vehicle only; S+Su, S rats given Su, 4 mg/kg/day; Nx+V, Nx rats receiving V; and Nx+Su, Nx rats receiving Su. Su caused no change in Group S. Seven and 45 days after renal ablation, renal cortical interstitium was expanded, in association with rarefaction of peritubular capillaries. Su did not worsen hypertension, proteinuria or interstitial expansion, nor did it affect capillary rarefaction, suggesting little angiogenic activity in this model. Nx animals exhibited glomerulosclerosis (GS), which was aggravated by Su. This effect could not be explained by podocyte damage, nor could it be ascribed to tuft hypertrophy or hyperplasia. GS may have derived from organization of capillary microthrombi, frequently observed in Group Nx+Su. Treatment with Su did not reduce the fractional glomerular endothelial area, suggesting functional rather than structural cell injury. Chronic VEGF inhibition has little effect on normal rats, but can affect glomerular endothelium when renal damage is already present.

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Section: Discussionsupporting

confidence: 89%

Chronic VEGF Blockade Worsens Glomerular Injury in the Remnant Kidney Model

et al. 2012

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“…These include cutaneous, vascular, and mucosal toxicities, such as hand–foot syndrome, skin rash, and hypertension, and endocrine toxicities like hypothyroidism [3, 4]. Moreover, abnormalities in laboratory tests, including cytopenias (leukopenia, neutropenia, anemia, and thrombocytopenia), and disruptions of renal and liver function, are also observed during sunitinib treatment [3–6]. …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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.

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“…A few data on the correlation between response to some tyrosine kinase inhibitors (imatinib, sunitinib) and macrocytosis occurrence have been published so far (1,(6)(7)(8). In case of other tyrosine kinase inhibitors such as: sorafenib and erlotinib -macrocytosis does not occur (7,8).…”

Section: Discussionmentioning

confidence: 99%

“…Macrocytosis develops at average after 3 cycles, which usually means 17 weeks of therapy with sunitinib (1). Macrocytosis was diagnosed regardless the type of neoplasm when sunitinib was used (1,(6)(7)(8). Sunitinib-induced macrocytosis is reversible with drug discontinuation (7).…”

Section: Discussionmentioning

confidence: 99%

Increased mean corpuscular volume as a predictor of response during bevacizumab treatment

Zygulska

Krzemieniecki

2012

Arch Oncol

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Background: Remission during sunitinib (a multikinase inhibitor and antiangiogenic drug) treatment correlates with appearance of macrocytosis. There are some suggestions that bevacizumab, an antiangiogenic drug, may result in macrocytosis as well. There are no published data available on the influence of bevacizumab on macrocytosis. This paper attempted to answer the question: does bevacizumab induce macrocytosis being a predictor of the response? Methods: Between August 2008 and August 2011, 53 patients (29 male and 24 female) were treated with bevacizumab in the combination with chemotherapy at the Oncological Department, University Hospital in Krakow, Poland. Efficacy of bevacizumab was assessed on the basis of the computer tomography scans performed every 3 months within the period of 12 months. Concurrently, mean corpuscular volume (MCV) was evaluated and correlated to the response of the treatment. Results: The percentage increase of MCV compared to baseline at 3, 6, 9 and 12 months was 3.7%, 9.2%, 8.7% and 11.8% respectively. The mean value of baseline MCV was 85.3 fl. The mean value of MCV at 3, 6, 9 and 12 months was 90.5 fl, 93 fl, 91.8 fl and 93.1 fl respectively. Macrocytosis did not occur in our study but an increase of MCV was observed within bevacizumab therapy. It was closely related to the response of the treatment. It seems that an increase of MCV can be a predictive agent of bevacizumab response. Conclusion: Bevacizumab does not induce macrocytosis. Increased MCV after treatment with bevacizumab is related to the treatment response. MCV can be a predictor of the response during bevacizumab treatment. A small number of the observed patients requires further investigations

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Hematologic Toxicity in Patients Treated with Sunitinib for Advanced Thyroid Cancer

Cited by 13 publications

References 18 publications

Chronic VEGF Blockade Worsens Glomerular Injury in the Remnant Kidney Model

Chronic VEGF Blockade Worsens Glomerular Injury in the Remnant Kidney Model

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

Increased mean corpuscular volume as a predictor of response during bevacizumab treatment

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