In vivo measurement of myocardial oxidative metabolism and blood flow does not show changes in cancer patients undergoing doxorubicin therapy.
OBJECTIVE
The aim was to investigate in patients receiving doxorubicin whether any alteration in myocardial oxidative metabolism or blood flow as assessed by positron emission tomography (PET) could be observed either after the first dose of the drug, or during its chronic administration.


METHODS
Six female non-heart-failure cancer patients treated with doxorubicin were included in a longitudinal study. Resting radionuclide cineangiography and PET scanning with carbon-11 acetate were performed the day before the initiation of doxorubicin treatment at a dosage of 50 mg/m2 every 3 weeks, and 3 weeks after the cumulative administration of 300 mg/m2 (chronic toxicity). In addition, PET was performed 24 h after the first administration of doxorubicin (evaluation of acute toxicity). Myocardial oxidative metabolism and blood flow were assessed by PET (acute and chronic toxicity), and left ventricular ejection fraction was measured by radionuclide angiography (chronic toxicity).


RESULTS
Using PET for both acute and chronic toxicity evaluations, no significant effect of doxorubicin was observed either on the flux through the tricarboxylic acid (TCA) cycle or on myocardial blood flow. However, systolic left ventricular function showed a small but significant impairment after the administration of 300 mg/m2 of doxorubicin.


CONCLUSIONS
Other hypotheses should be explored to better explain the predominant mechanisms of the cardiotoxicity of anthracyclines in humans.
Nony
P
P
Department of Clinical Pharmacology, Cardiovascular Hospital, Lyon, France. pn@upcl.univ-lyon1.fr
Guastalla
J P
JP
Rebattu
P
P
Landais
P
P
Lievre
M
M
Bontemps
L
L
Itti
R
R
Beaune
J
J
Andre-Fouet
X
X
Janier
M
M
D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D002952:Citric Acid Cycle / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004317:Doxorubicin / Q000009:adverse effects*; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010084:Oxidation-Reduction; D014055:Tomography, Emission-Computed
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin