Cardiac function evaluation in AMSA-treated patients.

Cardiac function was monitored by means of ECG and systolic time intervals in 13 patients submitted to treatment with 4'-(9-acridinylamino) methanesulfon-m-aniside (AMSA) without the classical reconstitution vehicle N1N-dimethylacetamide. ECG changes were represented by flattening of T waves (100%), sporadic atrial extrasystoles (23%), and sporadic or coupled ventricular premature beats (7.6%). These alterations were transient and not dose related. The systolic time interval ratio, recorded at the end of infusion and 2 h after drug administration, did not change significantly from pretreatment values. Systolic time intervals recorded in 6 patients after the mean cumulative dose of 550 mg/m2, and in 3 patients after the mean cumulative dose of 1000 mg/m2, did not change from mean basal values. Present data failed to confirm the occurrence of a significantly cardiotoxic activity of AMSA.

Preliminary evaluation of myocardial toxicity of 4'-deoxydoxorubicin: experimental and clinical results.

4'-deoxydoxorubicin (4'-deoxy-DXR), a new doxorubicin (DXR) analogue with interesting antineoplastic activity, was tested for its cardiotoxicity in guinea pigs and humans. In experiments on isolated guinea pig heart, which is considered a highly predictive model of acute anthracycline cardiotoxicity in humans, 4'-deoxy-DXR was found to be significantly less cardiotoxic than DXR. This effect was correlated with a lower degree of inhibition of the fast-exchanging calcium compartment and of the low affinity sarcolemmal calcium-binding sites. The preliminary study on 4'-deoxy-DXR in humans was conducted on 117 patients affected by advanced malignancies resistant to conventional chemotherapy. The drug was administered by bolus i.v. injection in doses ranging from 10 to 40 mg/m2 in the phase I study and in doses of 35 mg/m2 in the phase II study, which is still ongoing. Cardiologic evaluation consisted of recording of EKG, left ventricular systolic time intervals (STI), echocardiography and radionuclide ejection fraction. Preliminary data indicated a lower percentage of EKG abnormalities in comparison not only with DXR but also with other anthracycline analogues. Analysis of STI recorded 1 h after different doses of 4'-deoxy-DXR failed to show the dose-dependent effect on left ventricular function which has been described for DXR, thus confirming the lower acute cardiotoxic effect. Functional parameters serially measured to evaluate chronic cardiotoxicity in 15 patients who received more than 200 mg/m2 were not significantly different from basal values.

Possible enhancement of the cardiotoxicity of doxorubicin when combined with mitomycin C.

Forty-six patients with recurrent metastatic breast cancer were treated with a combination chemotherapy including doxorubicin and mitomycin C. Myocardial contractility was monitored by means of echocardiography. During therapy there was a progressive deterioration of myocardial function, and this phenomenon was found to be linearly correlated to the cumulative dose of doxorubicin. Six patients (13.8%) developed congestive heart failure during therapy; it occurred after the median cumulative dose of 322 mg/m2 (range 135-472). Possible risk factors of cardiomyopathy could be identified in only two patients. These results suggest that mitomycin C could enhance the cardiotoxicity of doxorubicin.

Preliminary echocardiographic and polygraphic evaluation of cardiac toxicity of 4'-epi-doxorubicin.

Data recorded by ECG, poly ECG, and echocardiography in 101 cancer patients treated with 4'-epi-doxorubicin are reported and compared with those previously obtained in a comparable group of 78 patients treated with doxorubicin. 4'-Epi-doxorubicin was administered by i.v. route in doses ranging from 50 to 90 mg/m2 in a three-weekly regimen; the maximum cumulative dose was 630 mg/m2. The results obtained demonstrate that this new antitumor anthracycline develops a lower acute cardiotoxic effect and suggest that 4'-epi-doxorubicin is endowed with a reduced chronic cardiotoxicity as compared to doxorubicin.