Functional cardiac changes including decreases in left ventricular ejection fraction (LVEF) and irreversible congestive heart failure can occur with NOVANTRONE. Cardiac toxicity may be more common in patients with prior treatment with anthracyclines, prior mediastinal radiotherapy, or with preexisting cardiovascular disease . Such patients should have regular cardiac monitoring of LVEF from the initiation of therapy. Cancer patients who received cumulative doses of 140 mg/m² either alone or in combination with other chemotherapeutic agents had a cumulative % probability of clinical congestive heart failure . In comparative oncology trials, the overall cumulative probability rate of moderate or severe decreases in LVEF at this dose was 13%.
Cytosine arabinoside combines a cytosine base with an arabinose sugar. It is an antimetabolic agent with the chemical name of 1β-arabinofuranosylcytosine . Certain sponges, where it was originally found, use arabinoside sugars to form a different compound (not part of DNA). Cytosine arabinoside is similar enough to human cytosine deoxyribose (deoxycytidine) to be incorporated into human DNA, but different enough that it kills the cell. Cytosine arabinoside interferes with the synthesis of DNA. Its mode of action is due to its rapid conversion into cytosine arabinoside triphosphate , which damages DNA when the cell cycle holds in the S phase (synthesis of DNA). Rapidly dividing cells, which require DNA replication for mitosis , are therefore most affected. Cytosine arabinoside also inhibits both DNA  and RNA polymerases and nucleotide reductase enzymes needed for DNA synthesis. Cytarabine is the first of a series of cancer drugs that altered the sugar component of nucleosides . Other cancer drugs modify the base.