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Journal of Clinical Oncology
Joanne L. Blum, MD
View Expert Commentary
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Melanie E. Royce, MD, PhD
Director, Hereditary Cancer Assessment Program and Multidisciplinary Breast Cancer Program
University of New Mexico Cancer Center
Albuquerque, NM
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Indications
XELODA (capecitabine) monotherapy is indicated for the treatment of patients with metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen or resistant to paclitaxel and for whom further anthracycline therapy is not indicated, eg, patients who have received cumulative doses of 400 mg/m2 of doxorubicin or doxorubicin equivalents. Resistance is defined as progressive disease while on treatment, with or without an initial response, or relapse within 6 months of completing treatment with an anthracycline-containing adjuvant regimen.
XELODA in combination with docetaxel is indicated for the treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing chemotherapy.
Boxed WARNING and Additional Important Safety Information
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Boxed Warning
Warfarin Interaction – Coagulopathy
- Patients receiving concomitant capecitabine and oral coumarin-derivative anticoagulant therapy should have their anticoagulant response (INR or prothrombin time) monitored frequently in order to adjust the anticoagulant dose accordingly.
- A clinically important XELODA-Warfarin drug interaction was demonstrated in a clinical pharmacology trial.
- Altered coagulation parameters and/or bleeding, including death, have been reported in patients taking XELODA concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon.
- Clinically significant increases in prothrombin time (PT) and INR have been observed in patients who were stabilized on anticoagulants at the time XELODA was introduced. These events occurred within several days and up to several months after initiating XELODA therapy, and infrequently within 1 month after stopping XELODA. These events occurred in patients with and without liver metastases.
- Age greater than 60 and a diagnosis of cancer independently predispose patients to an increased risk of coagulopathy.
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Contraindications
- XELODA is contraindicated in patients with known hypersensitivity to capecitabine or to any of its components or to 5-fluorouracil. XELODA is also contraindicated in patients with known dihydropyrimidine dehydrogenase (DPD) deficiency, or severe renal impairment.
Adverse Events
- In a single arm study of XELODA monotherapy in metastatic breast cancer, serious adverse events (grade 3/4) occurring in >5% of patients receiving XELODA (%) were lymphopenia (59), diarrhea (15), hand-foot syndrome (11), hyperbilirubinemia (11), fatigue (8), stomatitis (7), and dehydration (5). The most common adverse events for all grades occurring in >30% of patients receiving XELODA were lymphopenia (94), anemia (72), diarrhea (57), hand-foot syndrome (57), nausea (53), fatigue (41), dermatitis (37), and vomiting (37).
- In a phase 3 study of XELODA combination therapy (XELODA plus docetaxel) in metastatic breast cancer, serious adverse events (grade 3/4) occurring at a >2% higher incidence in patients receiving XELODA plus docetaxel vs docetaxel alone (%;%) were lymphocytopenia (89;84), hand-foot syndrome (24;1), stomatitis (<18;5), diarrhea (<15;<6), anemia (10;<6), hyperbilirubinemia (9;4), nausea (7;2), vomiting (5;2), constipation (2;0), and nail disorder (2;0). The most common adverse events for all grades occurring at a >5% higher incidence in patients receiving XELODA plus docetaxel vs docetaxel alone were diarrhea (67;48), stomatitis (67;43), hand-foot syndrome (63;8), nausea (45;36), thrombocytopenia (41;23), vomiting (35;24), abdominal pain (30;24), hyperbilirubinemia (20;6), weakness (16;11), dyspepsia (14;8), lacrimation increase (12;7), and appetite decrease (10;5).
Please see enclosed full XELODA Prescribing Information including Boxed Warning for additional Important Safety Information.
 Full Prescribing Information
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