First Quarter 2008 - Issues in Hematology - ION Solutions

XELODAEfficacy that makes a differenceEligible for only Medicare Part B coverage in oncologyIndicationsXELODA is indicated as a single agent for adjuvant treatment in patientswith Dukes’ C colon cancer who have undergone complete resection ofthe primary tumor when treatment with fluoropyrimidine therapy alone ispreferred. XELODA was non-inferior to 5-fluorouracil and leucovorin (5-FU/LV)for disease-free survival (DFS). Although neither XELODA nor combinationchemotherapy prolongs overall survival (OS), combination chemotherapy has beendemonstrated to improve disease-free survival compared to 5-FU/LV. Physiciansshould consider these results when prescribing single-agent XELODA in theadjuvant treatment of Dukes’ C colon cancer.XELODA is indicated as first-line treatment of patients with metastaticcolorectal carcinoma when treatment with fluoropyrimidine therapy aloneis preferred. Combination chemotherapy has shown a survival benefit comparedto 5-FU/LV alone. A survival benefit over 5-FU/LV has not been demonstrated withXELODA monotherapy. Use of XELODA instead of 5-FU/LV in combinations has notbeen adequately studied to assure safety or preservation of the survival advantage.XELODA monotherapy is indicated for the treatment of patients with metastaticbreast cancer resistant to both paclitaxel and an anthracycline-containingchemotherapy regimen or resistant to paclitaxel and for whom furtheranthracycline therapy is not indicated, eg, patients who have received cumulativedoses of 400 mg/m 2 of doxorubicin or doxorubicin equivalents. Resistance is definedas progressive disease while on treatment, with or without an initial response, or relapsewithin 6 months of completing treatment with an anthracycline-containing adjuvant regimen.XELODA in combination with docetaxel is indicated for the treatment ofpatients with metastatic breast cancer after failure of prior anthracyclinecontainingchemotherapy.Important Safety InformationWARNINGFor patients receiving XELODA and warfarin concomitantly, frequent monitoring of INR orprothrombin time (PT) is recommended. A clinically important drug interaction betweenXELODA and warfarin has been demonstrated. Altered coagulation parameters and/orbleeding and death have been reported. Clinically significant increases in PT and INR havebeen observed within days to months after starting XELODA, and infrequently within onemonth of stopping XELODA. These events occurred in patients with and without livermetastases. Age greater than 60 and a diagnosis of cancer independently predisposepatients to an increased risk of coagulopathy.Adverse EventsIn XELODA monotherapy for colon cancer in the adjuvant setting, the most common adverseevents for all grades (≥10%) in patients receiving XELODA (%) were hand-foot syndrome (60),diarrhea (47), nausea (34), stomatitis (22), fatigue (16), lethargy (16), vomiting (15), abdominalpain (14), and asthenia (10). Grade 3/4 adverse events (≥5%) in patients receiving XELODAwere hand-foot syndrome (17) and diarrhea (12). In XELODA monotherapy for metastaticcolorectal cancer, the most common adverse events (≥10%) in patients receiving XELODA (%)were anemia (80), diarrhea (55), hand-foot syndrome (54), hyperbilirubinemia (48), nausea (43),fatigue/weakness (42), abdominal pain (35), dermatitis (27), vomiting (27), appetite decrease (26),stomatitis (25), pyrexia (18), edema (15), constipation (14), dyspnea (14), neutropenia (13), pain (12),back pain (10), headache (10), gastrointestinal motility disorder (10), oral discomfort (10),peripheral sensory neuropathy (10), and eye irritation (13). Grade 3/4 adverse events (≥5%) inpatients receiving XELODA were hyperbilirubinemia (23), hand-foot syndrome (17), diarrhea (15),