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.
Department of Pulmonary Diseases, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. f.m.wachters@int.azg.nl
Floris M
FM
Wachters
Winette T A
WT
Van Der Graaf
Harry J M
HJ
Groen
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