Indications
XELODA is indicated as a single agent for adjuvant treatment in patients with Dukes' C colon cancer who have
undergone complete resection of the primary tumor when treatment with fluoropyrimidine therapy alone is
preferred. XELODA was non-inferior to 5-fluorouracil and leucovorin (5-FU/LV) for disease-free survival (DFS).
Physicians should consider results of combination chemotherapy trials, which have shown improvement in DFS and
overall survival (OS), when prescribing single-agent XELODA in the adjuvant treatment of Dukes' C colon
cancer.
XELODA is indicated as first-line treatment of patients with metastatic colorectal carcinoma when treatment with
fluoropyrimidine therapy alone is preferred. Combination chemotherapy has shown a survival benefit compared to
5-FU/LV alone. A survival benefit over 5-FU/LV has not been demonstrated with XELODA monotherapy. Use of XELODA
instead of 5-FU/LV in combinations has not been adequately studied to assure safety or preservation of the
survival advantage.
XELODA 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
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.
- Postmarketing reports have shown 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.
- XELODA is contraindicated in patients with known dihydropyrimidine dehydrogenase (DPD) deficiency, or severe
renal impairment. XELODA is also contraindicated in patients with known hypersensitivity to capecitabine or
to any of its components or to 5-fluorouracil.
- Additional serious adverse reactions include diarrhea, cardiotoxicity, hand-and-foot syndrome, and
hyperbilirubinemia. XELODA can cause fetal harm. Advise women of the potential risk to the fetus. Do not
treat patients with neutrophil counts <1.5 x 109/L or thrombocyte counts <100 x 109/L.
- The most common adverse reactions (≥30%) reported with XELODA were diarrhea, hand-and-foot syndrome,
nausea, vomiting, abdominal pain, fatigue/weakness, and hyperbilirubinemia. Other adverse reactions,
including serious adverse reactions, have been reported.
Monotherapy in Dukes’ C Stage (III) Colon Cancer
In a phase 3 study of XELODA monotherapy in colon cancer in the adjuvant setting, serious adverse events (grade
3/4) occurring in ≥5% of patients receiving either XELODA or 5-FU/LV (%;%) were increase in bilirubin
(20;7), hand-foot syndrome (17;<1), decrease in lymphocytes (13;13), diarrhea (12;14), decrease in
neutrophils/granulocytes (3;27), decrease in neutrophils (3;27), stomatitis (2;14), and neutropenia (<1;5). The
most common adverse events for all grades occurring in ≥30% of patients receiving either XELODA or 5-FU/LV
were hand-foot syndrome (60;9), diarrhea (47;65), nausea (34;47), and stomatitis (22;60). A total of 18 deaths
due to all causes occurred either on study or within 28 days of receiving study drug: 8 (0.8%) patients
randomized to XELODA and 10 (1.0%) randomized to 5-FU/LV.
Monotherapy in mCRC
In two phase 3 trials of XELODA monotherapy in metastatic colorectal cancer, serious adverse events (grade 3/4)
occurring in ≥5% of patients receiving either XELODA or 5-FU/LV (%;%) were hyperbilirubinemia (23;6),
hand-foot syndrome (17;1), diarrhea (15;12), abdominal pain (<10;5), vomiting (<5;<5), ileus (5;3), stomatitis
(<3;15), and neutropenia (3;21). The most common adverse events for all grades occurring in ≥30% of
patients receiving either XELODA or 5-FU/LV were anemia (80;79), diarrhea (55;61), hand-foot syndrome (54;6),
hyperbilirubinemia (48;17), nausea (43;51), fatigue/weakness (42;46), abdominal pain (35;31), vomiting (27;30),
appetite decrease (26;31), stomatitis (25;62), and neutropenia (13;46). A total of 82 deaths due to all causes
occurred either on study or within 28 days of receiving study drug: 50 (8.4%) patients randomized to XELODA and
32 (5.4%) randomized to 5-FU/LV.
Monotherapy in mBC
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).
Combination Therapy with Docetaxel in mBC
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).
You may report side effects to the FDA at (800) FDA-1088 or
www.fda.gov/medwatch. You may also report side
effects to Genentech at (888) 835-2555.
Please see the full Prescribing Information for Additional Important Safety Information.
