Breast cancer patients who have progressed through currently available chemotherapy will now have another treatment option
at their disposal. Ixabepilone (Ixempra), from Bristol-Myers Squibb, was recently approved by the Food & Drug Administration
for this subset of patients, both as monotherapy and in combination with capecitabine (Xeloda, Roche). Specifically, the new
entity is indicated in patients with metastatic or locally advanced breast cancer. If it is to be used as monotherapy, patients
should be resistant to anthracyclines, taxanes, and capecitabine. As a combination treatment with capecitabine, ixabepilone
is indicated for breast cancer resistant to both an anthracycline and a taxane.
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"Ixabepilone is the first in a new class of chemotherapy agents called epothilones," said Laura Boehnke Michaud, Pharm.D.,
BCOP, FASHP, clinical pharmacy specialist in breast oncology at the University of Texas M. D. Anderson Cancer Center. "They
function similarly to the taxanes, binding to beta-tubulin, preventing microtubule depolymerization, preventing mitosis, and
eventually leading to apoptosis," she explained. "They bind in a unique manner to beta-tubulin and appear to be active in
taxane-resistant tumor cell lines, tumor xenografts, and in patients with pretreated metastatic breast cancer."
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Results of a phase II trial that led to the approval of the drug as a monotherapy involved 126 patients with resistant breast
cancer. According to BMS, there was an objective partial response in 12.4% of 113 patients who were evaluated. A phase III
trial evaluating safety and efficacy of the drug as a combination treatment with capecitabine included 752 patients. Results
showed a statistically significant improvement in progression-free survival.
"Ixabepilone will more than likely be used as a single agent in metastatic breast cancer patients who have failed other standard
chemotherapy agents as salvage therapy," Michaud said. She believes that although the drug can be used with capecitabine,
the combination is quite toxic and may not be appropriate for the majority of patients. Patients with hepatic impairment comprise
one group at increased risk for developing neutropenia and other serious adverse reactions.According to the prescribing information, the combination of ixabepilone and capecitabine is contraindicated—due to increased
risk of toxicity and neutropenia-related death—in patients with AST or ALT >2.5 times the upper limit of normal (ULN) or with
bilirubin > one time the ULN. Caution should be used with ixabepilone as monotherapy in patients with AST or ALT levels >
five times ULN; the patients should receive a reduced dose depending on the degree of hepatic impairment.
Peripheral neuropathy is characterized as a common side effect of ixabepilone, occurring in 67% of patients on combination
treatment and 63% on monotherapy. According to the manufacturer, most cases emerge early in treatment—within the first three
cycles—and can be managed through dose reductions, delays, and treatment discontinuation. Patients with diabetes seem to be
at an increased risk of developing peripheral neuropathy.
Patients receiving ixabepilone should also be monitored for myelosuppression. Frequent peripheral blood cell counts are recommended,
and patients who experience severe neutropenia or thrombocytopenia should have their doses reduced. In addition, caution should
be exercised in patients with a history of cardiac disease due to reports of myocardial ischemia, ventricular dysfunction,
and supraventricular arrhythmia.
The wholesale list price of Ixempra (see http:// http://www.ixempra.com/) per cycle is $4,610, according to BMS, or between $18,440 and $23,050 per treatment course.
TIPS TO REMEMBER Ixempra
- The recommended dose of Ixempra is 40 mg/m2 infused intravenously over three hours every three weeks.
- Premedication with an H1 and H2 antagonist about one hour prior to Ixempra infusion is recommended. Patients who have experienced
a prior hypersensitivity reaction to Ixempra should also be premedicated with a corticosteroid.
- Frequent peripheral blood cell counts are recommended for patients receiving Ixempra.
- Ixempra should not be used in patients with baseline neutrophil count <1,500 cells/mm3 or a platelet count <100,000 cells/mm3.
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