To the Editor: We read with interest the article by Seidman et al 1 describing the risks of adverse cardiac events associated with trastuzumab therapy for metastatic breast cancer, published in the March 1, 2002, issue of the Journal of Clinical Oncology. In that retrospective review of records from 1,219 patients enrolled onto one of seven phase II or III clinical trials, the risk of adverse cardiac events was low (3% to 7%) when trastuzumab was prescribed alone. In contrast, the risk was higher when trastuzumab was combined with paclitaxel (13%) and inordinately high when it was combined with anthracyclines and cyclophosphamide (26%).From pathophysiologic and clinical perspectives, several aspects of this cardiotoxicity remain unclear. 2,3 For instance, data from clinical studies do not clarify whether cardiotoxicity develops early or whether it is related to a cumulative dose of treatment, as has been observed with anthracyclines. Likewise, the clinical course of the cardiomyopathic disorder after discontinuation of treatment has not been described.Since March 2001, we have followed prospectively 28 consecutive patients treated for metastatic breast cancer with trastuzumab, administered in an initial dose of 4 mg/m 2 followed by 2 mg/m 2 weekly, and paclitaxel, in a dose of 80 mg/m 2 , 6 out of 8 weeks. Surveillance of the cardiac status was by way of echocardiography, systematically performed at weekly intervals during the first month and then every 2 months by the same techniques and same operator, to ensure reproducibility of the measurements. The criterion threshold for detection of cardiotoxicity was a more than 10% decrease in left ventricular ejection fraction between two consecutive examinations. The 28 patients (mean age, 54 years; range, 40 to 70 years) had received an anthracycline, including doxorubicin in five patients, epirubicin in 11 patients, or mitoxantrone in 12 patients, as adjunctive therapy before being placed on the trastuzumab-paclitaxel combination. A more than 10% decrease in left ventricular ejection fraction was observed in four patients (14%), similar to the 13% incidence of adverse cardiac effects reported by Seidman et al. 1 In all cases, this decrease in left ventricular function appeared unexpectedly early. It was observed immediately after the first inductive course of therapy in two patients, after 2 weeks of treatment in one patient, and after 4 weeks in one patient. No progression of ventricular dysfunction was observed after withdrawal of therapy. Echocardiographic measurements have remained unchanged in two patients and have normalized within 4 months in the others. During long-term follow-up of the other 24 patients, including a mean number of courses of therapy of 20 (range, 12 to 54 courses), no evidence of cardiotoxicity was observed.This observation of very early, non-dose-dependent cardiotoxicity suggests the development of an acute inflammatory reaction resembling acute myocarditis. Like myocarditis, the disorder may resolve without sequelae, or evolve toward chron...

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Background: >Choroidal metastasis is the most common ocular tumor, in most cases related to breast and lung cancer. Radiotherapy (RT) mostly is the therapy of choice. However, there is a lack of data about the results of uniformly, prospective treated patients. Patients and Methods: Between November 1994 and September 1997, 37 patients with 49 metastatic eyes were enrolled into the study. 25 patients (68%) had unilateral and 12 patients (32%) had bilateral metastases. 21 patients had breast cancer as primary tumor, 12 patients lung cancer, and 4 patients other tumors. 3 patients were excluded from analysis, 34 patients with 46 involved eyes were available for analysis. 29 of those patients had symptomatic metastases, 5 patients had asymptomatic choroidal metastases. RT was performed with bi- or unilateral asymmetric fields, total dose was 40 Gy with a single dose of 2 Gy, 5 fractions per week. 12 patients (35%) had a chemotherapy following RT due to diagnosis of general tumor progression. Endpoints of the study were visual acuity (VA), local tumor control, survival, and side effects. Results: The median follow up was 6 months, 22 out of 34 patients died of metastatic disease. In 17 of symptomatic eyes (53%) an increase of VA and in 11 of symptomatic eyes (34%) a ‘no change’ was achieved. The local tumor control rate after 18 months was 83%. One patient with asymptomatic metastasis (1/14 eyes) developed symptoms until death. The median survival time was 15 months. Altogether, in 2 patients late side effects (6%) were observed (1 patients with bilateral retinopathy, 1 patient with optic nerve atrophy). Conclusions: RT with 40 Gy is highly effective in the treatment of symptomatic and asymptomatic choroidal metastases, VA was stable or improved in almost 90% of treated eyes. The rate of side effects is low.