Block sequential adriamycin CMF – optimal non-myeloablative chemotherapy for high risk adjuvant breast cancer?

After the publication of the 10-year survival data from Milan on the adjuvant use of the block sequential regimen consisting of four cycles of adriamycin followed by eight cycles of intravenous CMF, many centres adopted this as standard of care for high risk, multiple node-positive breast cancer. For this reason it was identified as the standard arm for the Anglo-Celtic adjuvant high-dose chemotherapy trial. This study reports on the experience of this regimen in 329 women with early breast cancer involving at least four axillary nodes, who were treated outside any adjuvant chemotherapy trial. At a median follow-up of 3 years, the overall 5-year disease-free survival is 61%, and the overall survival is 70%. These data confirm the efficacy of this regimen in non-trial patients, and, for the same high risk subgroup, indicate that this approach offers an outcome at least as good as that seen in the CALGB 9344 AC-Taxol arm, and the NCIC days 1 and 8 CEF.     

Cardiac abnormalities 15 years and more after adriamycin therapy in 229 childhood survivors of a solid tumour at the Institut Gustave Roussy

The purpose of this paper was to determine the cardiac status in children 15 years or more after adriamycin therapy for a solid tumour. Of the 447 pts, 229 pts were fully studied and 218 were not. The following cardiac evaluations were proposed to all the 447 consecutive patients (pts): (1) cardiac Doppler US by one of two expert cardiologists; (2) cardiac rhythm and conduction abnormalities including 24-hour holter ECG; (3) (131)l-mlBG myocardial scintigraphy; (4) serum brain natriuretic peptide levels at rest; (5) an exercise test with VO(2) max measurement. The radiation doses delivered to 6 points in the heart were estimated for all patients who had received radiotherapy. Congestive heart failure was diagnosed in 24 of 229 (10%) evaluated pts, with a median interval of 15 years (0.3-24 years) from the first symptom after adriamycin treatment. Among the 205 remaining pts, 13 asymptomatic pts (6%) had severe (n=4) (FS<20%) or marked (n=9) (20< or =FS<25%) systolic dysfunction. In the 192 others, the median meridional end-systolic wall stress was 91 (53-135) and it exceeded 100 g cm(-2) in 52 pts. Using a Cox model, only the cumulative dose of adriamycin and the average radiation dose to the heart, were identified as risk factors for a pathological cardiac status. In conclusion, the risk of cardiac failure or severe abnormalities increases with adriamycin treatment, radiotherapy and time since treatment, even after a follow-up of 15 years or more. In our series, after an average follow-up of 18 years, 39% of the children had a severe cardiac dysfunction or major ventricular overload conditions. The risk increases with the dose of adriamycin and radiation received to the heart, without evidence for threshold.     

炙甘草汤对含阿霉素新辅助化疗乳腺癌患者心脏的影响

目的观察炙甘草汤对含阿霉素新辅助化疗乳腺癌患者心脏的影响。方法60例乳腺癌初治患者按治疗方式分成A组（单纯新辅助化疗）30例,B组（新辅助化疗＋炙甘草汤）30例,在治疗前后检测患者的心脏状态变化。结果①A组治疗后血液心肌损伤标志物cTnI、LDH、AST、CK、CK—MB、α—HBD明显上升（P〈0．05）,B组治疗后血液心肌损伤标志物无明显变化（P〉0．05）。②两组间治疗前血液心肌损伤标志物的变化差异无统计学意义（P〉0．05）,治疗后变化有统计学意义（P〈0．05）。③A组治疗后LVEF、E／A值下降,但差异无统计学意义（P〉0．05）,B组治疗后LVEF、E／A值无明显变化（P〉0．05）。两组间患者治疗前后的LVEF和E／A值变化不明显,差异无统计学意义（P〉0．05）。结论含阿霉素新辅助化疗使乳腺癌患者心肌细胞明显受损,联合炙甘草汤治疗能使心肌细胞损伤得到改善。     

炙甘草汤预防蒽环类药物心脏毒性的临床观察

目的：研究炙甘草汤改善含蒽环类方案化疗的乳腺癌患者心脏毒性的临床效果。方法：收集40例接受含蒽环类方案化疗的乳腺癌患者的病案资料,根据随机数字表法,将患者随机分为单纯组和联合治疗组,记录并比较两组患者化疗前和随后第2、4、6周期治疗后的 LVEF、BNP、CK - MB、cTnT、心电图等的变化。结果：所有患者均未出现充血性心力衰竭（ CHF）。两组患者,随着治疗周期的延长,LVEF 呈下降趋势（P ﹤0.05）,cTnT、BNP 及 CK - MB 呈上升趋势（P ﹤0.05）。结论：炙甘草汤能有效改善蒽环类药物化疗所致的心脏毒性,且未观察到毒副反应增加。     

Early detection of anthracycline induced cardiotoxicity in asymptomatic patients with normal left ventricular systolic function: autonomic versus echocardiographic variables

OBJECTIVE: To investigate left ventricular dysfunction in patients who had been treated with anthracycline based chemotherapy. METHODS: Autonomic function was compared with left ventricular diastolic function in 20 asymptomatic women with normal systolic function (left ventricular ejection fraction (LVEF) > 0.50) treated for breast cancer with high dose anthracycline based chemotherapy, and 20 age matched healthy controls. Left ventricular diastolic function was assessed echocardiographically by measuring the early peak flow velocity to atrial peak flow velocity ratio, isovolumic relaxation time, and deceleration time. Heart rate variability analysis was assessed for time domain and frequency domain parameters. RESULTS: The mean (SD) age of the patients was 45 (7) years and the mean LVEF was 0.59 (0.06). The time interval after the end of chemotherapy was 29 (27) months. One or more diastolic variables were abnormal in 50% of the patients. Heart rate variability was abnormal in 85% of patients. Mean values of both time domain and frequency domain parameters were decreased (p < 0.05), in particular the parasympathetic indices. CONCLUSIONS: Autonomic impairment occurs in a large proportion of asymptomatic patients with normal systolic left ventricular function after high dose anthracycline based chemotherapy. In particular, heart rate variability analysis may be a sensitive tool to identify the first signs of cardiotoxicity in these patients.