Proactive management of adverse events maintains the clinical benefit of ixabepilone.
Ixabepilone is a novel microtubule-stabilizing agent with clinical efficacy in advanced breast cancer, including patients whose disease has progressed on prior anthracyclines and taxanes. The safety profile of single-agent ixabepilone and combination ixabepilone plus capecitabine therapy is reviewed, outlining the steps to effectively manage and prevent common adverse events. Ixabepilone is generally well tolerated, and importantly, its toxicity profile does not overlap with that of capecitabine. Peripheral sensory neuropathy and neutropenia are the most common toxicities associated with ixabepilone; both can be effectively managed by monitoring patients and then, depending on severity, instituting a treatment delay until recovery and reducing the ixabepilone dose for subsequent treatment cycles. Ixabepilone dose reductions are recommended for most grade 3 events, excluding transient fatigue, arthralgia, and myalgia, whereas treatment discontinuation is recommended for persistent grade 3 neuropathy or any grade 4 nonhematological toxicity. Because ixabepilone exposure is greater in patients with hepatic impairment and those receiving concomitant strong cytochrome P-450 CYP3A4 inhibitors, dose adjustments and restrictions are recommended according to the degree of hepatic impairment, whether ixabepilone is administered alone or in combination with capecitabine, and whether a strong CYP3A4 inhibitor is being coadministered. Patients should be premedicated with oral H(1) and H(2) antihistamines to prevent hypersensitivity reactions. Unlike taxanes, corticosteroid premedication is not required unless a hypersensitivity reaction occurred during a previous cycle or during treatment with another Cremophor-containing agent. By effectively managing adverse events and taking steps to minimize them, clinicians can ensure that patients derive the maximum benefit from ixabepilone therapy.
Yardley
Denise A
DA
Breast Cancer Research, Sarah Cannon Research Institute, 250 25th Avenue North, Suite 110, Nashville, TN 37203, USA. dyardley@tnonc.com
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001773:Blood Cells / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D034261:Epothilones / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D050257:Tubulin Modulators / Q000009:adverse effects*
D065692:Cytochrome P-450 CYP3A Inhibitors; D034261:Epothilones; D050257:Tubulin Modulators; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C430592:ixabepilone