Cardiotoxicity in advanced non-small cell lung cancer patients treated with platinum and non-platinum based combinations as first-line treatment.
BACKGROUND
One of the major dose-limiting toxicities of anthracyclines is cardiotoxicity due to irreversible cardiomyopathy. Whether cisplatin-based treatment induces caridiotoxicity in the short term, especially in non-small cell lung cancer (NSCLC) patients with cardiovascular comorbidity, has not been studied previously. The aim of this study was to evaluate cardiotoxicity in advanced NSCLC patients receiving cisplatin-gemcitabine (CG) or epirubicin-gemcitabine (EG) as first-line treatment.


METHODS
Patients were randomised to receive gemcitabine 1125 mg/m2 (days 1 and 8) plus either cisplatin 80 mg/m2 (day 2) or epirubicin 100 mg/m2 (day 1) every 3 weeks for a maximum of 5 cycles. Patients had to have a left ventricular ejection fraction (LVEF) > 45%, measured by multiple gated acquisition (MUGA) scan. A second MUGA scan was performed 12 weeks after the end of treatment.


RESULTS
Sixty-nine patients were included. The mean total dose of cisplatin was 349 mg/m2 and of epirubicin 452 mg/m2. The mean difference in decline in LVEF from baseline was 2% in the CG arm versus 6% in the EG arm (p=0.016). Clinically evident cardiac failure was not observed during 12 months follow-up. No correlation was found with total drug doses administered. In patients with a history of cardiac disease a trend towards a higher decrease in LVEF was observed.


CONCLUSIONS
Although in the EG arm the LVEF significantly declined and in the CG arm a trend for LVEF to decline was observed, the risk of cardiac failure is limited in advanced NSCLC patients.
Wachters
Floris M
FM
Department of Pulmonary Diseases, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. f.m.wachters@int.azg.nl
Van Der Graaf
Winette T A
WT
Groen
Harry J M
HJ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D015637:Gated Blood-Pool Imaging; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016277:Ventricular Function, Left / Q000187:drug effects; D000093542:Gemcitabine
D003841:Deoxycytidine; D015251:Epirubicin; D002945:Cisplatin; D000093542:Gemcitabine