1253 Tyrosine kinase inhibitor (TKI)-induced macrocytosis

Schallier, D.; Trullemans, Fabienne; Fontaine, Christel; Decoster, Lynn; DeGreve, J

doi:10.1016/s1359-6349(09)70465-3

Cited by 8 publications

(21 citation statements)

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“…Potential causes should include therapy-induced hypothyroidism, folic acid and cobalamin deficiencies, and sunitinib’s inhibition of c-Kit kinase [11]. …”

Section: Discussionmentioning

confidence: 99%

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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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“…Potential causes should include therapy-induced hypothyroidism, folic acid and cobalamin deficiencies, and sunitinib’s inhibition of c-Kit kinase [11]. …”

Section: Discussionmentioning

confidence: 99%

“…In addition to lower RBC and HGB counts, authors have noted increases in MCV, which were reversible after treatment completion [11]. The mechanism that causes this phenomenon has not yet been fully explained.…”

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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“…Elevation of MCV values has been observed with sunitinib, but is uncommon with sorafenib therapy [14]. In addition, patients who have hypothyroidism tend to have a greater MCV increase than those who remain euthyroid [15].…”

Section: Original Researchmentioning

confidence: 99%

Clinical significance of sunitinib‐associated macrocytosis in metastatic renal cell carcinoma

et al. 2016

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Increases in the mean corpuscular volume (MCV) have been observed in patients with metastatic renal cell carcinoma (mRCC) on tyrosine kinase inhibitor (TKI) treatment; however, its association with progression‐free‐survival (PFS) is unknown. We aimed to characterize TKI‐associated macrocytosis in mRCC and its relationship with PFS. Retrospective review of data on macrocytosis and thyroid dysfunction on mRCC patients treated with sunitinib and/or sorafenib. These results are evaluated in the context of our previous report on the association of hypothyroidism in this setting. We assessed PFS as clinically defined by the treating physician. Seventy‐four patients, 29 of whom received both drugs, were included. A treatment period was defined as time from initiation to discontinuation of either sunitinib or sorafenib; 103 treatment periods [sorafenib (47), sunitinib (56)] were analyzed. Macrocytosis was found in 55 and 8% of sunitinib‐ and sorafenib‐treated patients, respectively, P < 0.001. The median time to developing macrocytosis was 3 months (m, range 1–7). Median PFS in sunitinib‐treated patients was 11 m (95% CI: 6–19). Median PFS was higher among those with macrocytosis compared to normocytosis (21 m [95% CI: 11–25] vs. 4 m [95% CI: 3–8] P = 0.0001). Macrocytosis and hypothyroidism were two significant predictors of PFS. The greatest difference in PFS among all patients was observed in patients with both macrocytosis and hypothyroidism (25 m), compared to the normocytic and euthyroid patients (5 m) (P < 0.0001). Sunitinib‐related macrocytosis was associated with prolonged PFS, and concurrent development of hypothyroidism and macrocytosis further prolonged PFS. Increased MCV may have a role as a predictive biomarker for sunitinib. Prospective studies accounting for other known prognostic factors are needed to confirm this finding.

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“…Macrocytosis has been reported in a case series of patients taking imatinib for GIST [28]. All patients taking imatinib developed macrocytosis and the percentage increases in mean corpuscular volume (MCV) after 3, 6, 9, and 12 months of therapy were 0.7%, 5.6%, 5.9%, and 5% respectively.…”

Section: Other Hematologic Toxicitiesmentioning

confidence: 95%

“…Her ITP resolved after drug discontinuation. Macrocytosis has also been described in patients taking sunitinib [28,73]. An institutional case series of all patients treated with sunitinib for RCC, breast cancer, and GIST reported development of macrocytosis in all cases.…”

Section: Other Hematologic Toxicitiesmentioning

confidence: 96%

Hematologic toxicities of small molecule tyrosine kinase inhibitors

2011

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Small molecule tyrosine kinase inhibitors (TKIs) are potent anti-cancer targeted therapies. TKIs are considered safe and efficacious therapeutic modalities, and are generally tolerated well. However, they are associated with certain side effects including hematologic toxicities such as anemia, macrocytosis, neutropenia, thrombocytopenia, hemolytic anemia, bone marrow aplasia and necrosis. Thrombotic microangiopathy, arterial thromboembolism and splenic infarction can also occur following treatment with TKIs. Cytopenias are the most common adverse effects associated with these agents, and other hematologic toxicities are not frequent. It is essential for clinicians to monitor patients closely, and recognize those side effects as early as possible, in order to improve efficacy of small molecule TKIs and optimize outcomes. This article summarizes hematologic toxicities associated with the commonly used small molecule TKIs. It also provides practical strategies for the management of these toxicities.

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1253 Tyrosine kinase inhibitor (TKI)-induced macrocytosis

Cited by 8 publications

References 0 publications

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

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

Clinical significance of sunitinib‐associated macrocytosis in metastatic renal cell carcinoma

Hematologic toxicities of small molecule tyrosine kinase inhibitors

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