Brenda,
Here is the warning carried within the herceptin prescribing information:
WARNINGS Cardiomyopathy Herceptin can cause left ventricular cardiac dysfunction. Cardiac dysfunction in patients receiving Herceptin therapy can be serious with disabling cardiac failure, death, and mural thrombosis leading to stroke (see
BOXED WARNINGS: Cardiomyopathy).
Among women receiving adjuvant therapy for breast cancer in Study 1, 16% (136/844) of patients discontinued Herceptin therapy due to clinical evidence of myocardial dysfunction or significant decline in LVEF (see
DOSAGE AND ADMINISTRATION: Dose Modifications). There was one death due to cardiomyopathy among patients receiving Herceptin. If Herceptin therapy is discontinued for left ventricular cardiac dysfunction, patients should be closely monitored for evidence of clinical deterioration and further decline in left ventricular function.
Among 32 patients receiving adjuvant chemotherapy (Studies 1 and 2) with clinical cardiac events as determined by ACREC, one patient died of cardiomyopathy and all other patients were receiving cardiac medication at last follow‑up. Approximately half of the surviving patients had recovery to a normal LVEF (defined as ≥ 50%) on continuing medical management at the time of last follow‑up. The safety of continuation or resumption of Herceptin in patients with Herceptin‑induced left ventricular cardiac dysfunction has not been studied.
In the adjuvant setting, among patients who completed AC chemotherapy and received at least one dose of paclitaxel, 2% [32/1677] of patients in the Herceptin arm and 0.4% [7/1600] of patients in the control arm experienced clinically symptomatic, laboratory‑confirmed cardiomyopathy as determined by an external review committee (ACREC).
Among patients with metastatic breast cancer, the incidence of CHF was 11% versus 1% in patients receiving paclitaxel with or without Herceptin and 28% versus 7% in patients receiving AC chemotherapy with or without Herceptin, respectively. The incidence of CHF in patients with metastatic breast cancer receiving Herceptin monotherapy was 7%.
An exploratory analysis for risk factors for symptomatic cardiomyopathy was conducted in patients receiving adjuvant treatment for breast cancer. The analysis is limited by the number and type of variables collected and how they were defined. Declining LVEF to below the lower limit of normal after completion of AC chemotherapy or during Herceptin treatment, a reported history of prior or concurrent use of anti‑hypertensive medications, and increasing age were associated with an increased risk of Herceptin‑induced symptomatic cardiomyopathy. Similar limited analyses in patients receiving chemotherapy for metastatic breast cancer identified prior cardiotoxic therapy (e.g., anthracycline or radiation therapy to the chest) and increasing age as potentially associated with an increased risk of Herceptin‑induced CHF.
Candidates for treatment with Herceptin should undergo a thorough baseline cardiac assessment, including history, physical examination, and an assessment of LVEF by echocardiogram or MUGA scan. Patients receiving Herceptin should undergo frequent monitoring for deteriorating left ventricular function. The following recommended schedule is consistent with that used in Studies 1 and 2: at baseline prior to AC chemotherapy, immediately prior to initiation of Herceptin, 3 months after initiation of Herceptin with paclitaxel, 3 months after initiation of Herceptin monotherapy, and 3 months after completion of Herceptin monotherapy. More frequent monitoring should be employed in patients with preexisting cardiac dysfunction. Monitoring will not identify all patients who will develop cardiac dysfunction.