Is There More for Us to Learn From Oncology?

Abstract

Decades of basic and clinical research have improved the cure rates of many forms of cancer, particularly childhood malignancies. An unintended consequence of this success is the fact that cancer survivors are often left with increased risk of cardiovascular disease, particularly congestive heart failure, after the use of anthracycline antibiotic chemotherapeutics. Discovered >50 years ago, these agents have enjoyed widespread use in solid and hematologic malignancies for >30 years. The cardiac effects of these drugs remain a dose-limiting toxicity and can be neither predicted nor prevented. Oncology has adapted by reducing the total dose to limit exposure and developing cotreatments that reduce cardiac damage.1 This well-documented problem, which continues to induce cardiac dysfunction severe enough to warrant heart transplantation, is tolerated in part because of the efficacy of anthracyclines as important components of chemotherapy regimens. Studies examining possible mechanisms for anthracycline cardiac toxicity have been occurring for decades and have revealed many aspects of cardiac biology. Despite these efforts, there is no generally accepted mechanism for how these drugs cause heart failure.2 Article see p 675 A general construct for anthracycline-induced cardiac toxicity is that some form of cardiac injury occurs with every exposure. Compensatory changes at the cellular and subcellular levels allow recovery, permitting function to return to “normal” under resting conditions. Exercise stress–induced cardiac reserve is abnormal after anthracycline exposure, even when resting function appears normal.3 This conceptual view is further supported by the finding that persons at greatest risk are those with limited reserve such as patients with hypertension and old age.4 Thus, anthracycline exposure leads to a subclinical cardiomyopathy that manifests itself variably, depending on a number of factors, including total anthracycline dose and reserve. A puzzle from this perspective is why children, who perhaps have the greatest cardiac reserve, are also …