Impaired coronary flow reserve in metastatic cancer patients treated with sunitinib.
OBJECTIVE
Hypertension is one of the major side effects of sunitinib, an angiogenesis inhibitor used in the treatment of metastatic renal cell carcinomas (mRCC) and gastrointestinal stromal tumors (GIST). Endothelial dysfunction, an early and reversible event in the pathogenesis of atherosclerosis, is suggested to be one of the possible underlying mechanisms of hypertension caused by angiogenesis inhibitors. Coronary flow reserve (CFR) measurement by trans-thoracic Doppler echocardiography (TTDE) reflects coronary microvascular and endothelial functions, as a cheaper and an easy screening test. We have used TTDE to evaluate endothelial function and coronary microvascular function in mRCC and GIST patients under sunitinib treatment.


METHODS
Eighteen metastatic cancer patients (16 mRCC and 2 GIST) on sunitinib treatment and 27 healthy subjects were enrolled in this cross-sectional study. Thyroid stimulating hormone (TSH), lipid profile, creatinine, hemoglobin, glucose, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anthropometric and physical parameters of patients were recorded. CFR recordings were performed by the Vivid 7 echocardiography device.


RESULTS
CFR was significantly lower in patients when compared with controls (1.82±0.4 vs 2.71±0.8, respectively; p < 0.001). Impaired CFR was found in 13 (72%) patients whereas all controls had normal CFR values. CFR was inversely correlated with the duration of sunitinib treatment (r=-0.36, p =0.01), high sensitivite (hs) CRP (r = -0.574, p =0.01) and ESR (r = - 0.5, p = 0.02).


CONCLUSIONS
Our findings indicate that CFR is significantly impaired in cancer patients on sunitinib treatment. There is an inverse correlation between CFR and duration of sunitinib treatment and inflammation markers.
Department of Medical Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey.
F
F
Sen
I
I
Yildiz
M
M
Basaran
M
M
Ekenel
F
F
Oz
L
L
Kilic
B
B
Toz
A
A
Gurdal
H
H
Camlica
S
S
Bavbek
H
H
Oflaz
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001783:Blood Flow Velocity / Q000187:drug effects; D001799:Blood Sedimentation / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000150:complications* / Q000188:drug therapy / Q000556:secondary; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000473:pathology; D016022:Case-Control Studies; D003326:Coronary Circulation / Q000187:drug effects*; D003430:Cross-Sectional Studies; D015150:Echocardiography, Doppler; D005260:Female; D005500:Follow-Up Studies; D046152:Gastrointestinal Stromal Tumors / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011758:Pyrroles / Q000009:adverse effects*; D000077210:Sunitinib
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib