Details
Stereochemistry | ACHIRAL |
Molecular Formula | C29H26ClFN4O4S.2C7H8O3S.H2O |
Molecular Weight | 943.476 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
O.CC1=CC=C(C=C1)S(O)(=O)=O.CC2=CC=C(C=C2)S(O)(=O)=O.CS(=O)(=O)CCNCC3=CC=C(O3)C4=CC=C5N=CN=C(NC6=CC=C(OCC7=CC=CC(F)=C7)C(Cl)=C6)C5=C4
InChI
InChIKey=XNRVGTHNYCNCFF-UHFFFAOYSA-N
InChI=1S/C29H26ClFN4O4S.2C7H8O3S.H2O/c1-40(36,37)12-11-32-16-23-7-10-27(39-23)20-5-8-26-24(14-20)29(34-18-33-26)35-22-6-9-28(25(30)15-22)38-17-19-3-2-4-21(31)13-19;2*1-6-2-4-7(5-3-6)11(8,9)10;/h2-10,13-15,18,32H,11-12,16-17H2,1H3,(H,33,34,35);2*2-5H,1H3,(H,8,9,10);1H2
DescriptionCurator's Comment: Description was created based on several sources, including
http://adisinsight.springer.com/drugs/800015425
Curator's Comment: Description was created based on several sources, including
http://adisinsight.springer.com/drugs/800015425
Lapatinib is a small molecule and a member of the 4-anilinoquinazoline class of kinase inhibitors. It is present as the monohydrate of the ditosylate salt (trade name TYKERB). Lapatinib is dual inhibitor of the EGFR (epidermal growth factor receptor; also called HER1 or ErbB1) and HER2 receptor tyrosine kinases. Lapatinib was developed by GlaxoSmithKline, however, Novartis subsequently acquired all the rights to the drug from GlaxoSmithKline. TYKERB is indicated in combination therapy for the treatment of metastatic breast cancer that overexpresses the HER2 receptor.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25977884
Curator's Comment: Increased lapatinib uptake was observed in brain metastases but not in normal brain.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL203 |
3.0 nM [Ki] | ||
Target ID: CHEMBL1824 |
13.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | TYKERB Approved UseTYKERB® is indicated in combination with: •capecitabine for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab. Limitation of Use: Patients should have disease progression on trastuzumab prior to initiation of treatment with TYKERB in combination with capecitabine. •letrozole for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer that overexpresses the HER2 receptor for whom hormonal therapy is indicated. TYKERB in combination with an aromatase inhibitor has not been compared to a trastuzumab-containing chemotherapy regimen for the treatment of metastatic breast cancer. TYKERB, a kinase inhibitor, is indicated in combination with: (1) •capecitabine, for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab. Limitation of Use: Patients should have disease progression on trastuzumab prior to initiation of treatment with TYKERB in combination with capecitabine. •letrozole for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer that overexpresses the HER2 receptor for whom hormonal therapy is indicated. TYKERB in combination with an aromatase inhibitor has not been compared to a trastuzumab-containing chemotherapy regimen for the treatment of metastatic breast cancer. Launch Date2007 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.43 μg/mL |
1250 mg 1 times / day steady-state, oral dose: 1250 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
LAPATINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
36.2 μg × h/mL |
1250 mg 1 times / day steady-state, oral dose: 1250 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
LAPATINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
24 h |
1250 mg 1 times / day steady-state, oral dose: 1250 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
LAPATINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1% |
LAPATINIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
1250 mg 1 times / day steady, oral MTD Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: whole brain radiotherapy Sources: |
unhealthy, 50 years (range: 30–78 years) n = 27 Health Status: unhealthy Condition: (HER2)-positive breast cancer Age Group: 50 years (range: 30–78 years) Sex: F Population Size: 27 Sources: |
DLT: Rash, Diarrhea... Dose limiting toxicities: Rash (grade 3, 2 patients) Sources: Diarrhea (grade 3, 2 patients) Hypoxia (grade 3, 1 patient) Pulmonary embolus (grade 4, 2 patients) |
1500 mg 1 times / day steady, oral Dose: 1500 mg, 1 times / day Route: oral Route: steady Dose: 1500 mg, 1 times / day Co-administed with:: whole brain radiotherapy Sources: |
unhealthy, 50 years (range: 30–78 years) n = 5 Health Status: unhealthy Condition: (HER2)-positive breast cancer Age Group: 50 years (range: 30–78 years) Sex: F Population Size: 5 Sources: |
DLT: Mucositis, Rash... Dose limiting toxicities: Mucositis (grade 3, 2 patients) Sources: Rash (grade 3, 2 patients) |
1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Disc. AE: Diarrhea... Other AEs: Diarrhea, Diarrhea... AEs leading to discontinuation/dose reduction: Diarrhea (grade 4, 1%) Other AEs:Diarrhea (all grades, 65%) Sources: Diarrhea (grade 3, 13%) Nausea (all grades, 44%) Nausea (grade 3, 2%) Vomiting (all grades, 26%) Vomiting (grade 3, 2%) Stomatitis (all grades, 14%) Dyspepsia (all grades, 11%) Dyspepsia (grade 3, <1%) Palmar-plantar erythrodysesthesia syndrome (all grades, 53%) Palmar-plantar erythrodysesthesia syndrome (grade 3, 12%) Rash (all grades, 28%) Rash (grade 3, 2%) Dermatitis acneiform (grade 3, <1%) Dry skin (all grades, 10%) Mucosal inflammation (all grades, 15%) Pain in extremity (all grades, 12%) Pain in extremity (grade 3, 1%) Back pain (all grades, 11%) Back pain (grade 3, 1%) Dyspnea (all grades, 12%) Dyspnea (grade 3, 3%) Insomnia (all grades, 10%) Insomnia (grade 3, <1%) Hepatotoxicity (severe|grade 5) Bilirubin total increased (grade 3, 4%) Bilirubin total increased (grade 1-2, 41%) AST increased (grade 3, 2%) AST increased (grade 4, <1%) AST increased (grade 1-2, 46%) ALT increased (grade 3, 2%) ALT increased (grade 1-2, 35%) |
1800 mg 1 times / day steady, oral MTD Dose: 1800 mg, 1 times / day Route: oral Route: steady Dose: 1800 mg, 1 times / day Sources: |
unhealthy, 60 years (range: 37 – 73 years) n = 6 Health Status: unhealthy Condition: Solid Tumors Age Group: 60 years (range: 37 – 73 years) Sex: M+F Population Size: 6 Sources: |
DLT: Diarrhea, Gamma GT increased... Other AEs: Stomatitis, Rash... Dose limiting toxicities: Diarrhea (grade 3, 2 patients) Other AEs:Gamma GT increased (grade 3, 1 patient) Stomatitis (grade 1, 1 patient) Sources: Rash (grade 2, 2 patients) Seborrheic dermatitis (grade 1, 1 patient) Paronychia (grade 1, 1 patient) Anorexia (grade 1, 3 patients) Lymphocyte count decreased (grade 1, 1 patient) |
1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: Letrozole(2.5 mg/day) Sources: |
unhealthy, 63 years n = 111 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 63 years Sex: F Population Size: 111 Sources: |
Other AEs: Hepatotoxicity, Bilirubin total increased... Other AEs: Hepatotoxicity (severe|grade 5) Sources: Bilirubin total increased (grade 3, <1%) Bilirubin total increased (grade 4, <1%) Bilirubin total increased (grade 1-2, 20%) AST increased (grade 3, 6%) AST increased (grade 1-2, 47%) ALT increased (grade 3, 5%) ALT increased (grade 4, <1%) ALT increased (grade 1-2, 40%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Hypoxia | grade 3, 1 patient DLT |
1250 mg 1 times / day steady, oral MTD Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: whole brain radiotherapy Sources: |
unhealthy, 50 years (range: 30–78 years) n = 27 Health Status: unhealthy Condition: (HER2)-positive breast cancer Age Group: 50 years (range: 30–78 years) Sex: F Population Size: 27 Sources: |
Diarrhea | grade 3, 2 patients DLT |
1250 mg 1 times / day steady, oral MTD Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: whole brain radiotherapy Sources: |
unhealthy, 50 years (range: 30–78 years) n = 27 Health Status: unhealthy Condition: (HER2)-positive breast cancer Age Group: 50 years (range: 30–78 years) Sex: F Population Size: 27 Sources: |
Rash | grade 3, 2 patients DLT |
1250 mg 1 times / day steady, oral MTD Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: whole brain radiotherapy Sources: |
unhealthy, 50 years (range: 30–78 years) n = 27 Health Status: unhealthy Condition: (HER2)-positive breast cancer Age Group: 50 years (range: 30–78 years) Sex: F Population Size: 27 Sources: |
Pulmonary embolus | grade 4, 2 patients DLT |
1250 mg 1 times / day steady, oral MTD Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: whole brain radiotherapy Sources: |
unhealthy, 50 years (range: 30–78 years) n = 27 Health Status: unhealthy Condition: (HER2)-positive breast cancer Age Group: 50 years (range: 30–78 years) Sex: F Population Size: 27 Sources: |
Mucositis | grade 3, 2 patients DLT |
1500 mg 1 times / day steady, oral Dose: 1500 mg, 1 times / day Route: oral Route: steady Dose: 1500 mg, 1 times / day Co-administed with:: whole brain radiotherapy Sources: |
unhealthy, 50 years (range: 30–78 years) n = 5 Health Status: unhealthy Condition: (HER2)-positive breast cancer Age Group: 50 years (range: 30–78 years) Sex: F Population Size: 5 Sources: |
Rash | grade 3, 2 patients DLT |
1500 mg 1 times / day steady, oral Dose: 1500 mg, 1 times / day Route: oral Route: steady Dose: 1500 mg, 1 times / day Co-administed with:: whole brain radiotherapy Sources: |
unhealthy, 50 years (range: 30–78 years) n = 5 Health Status: unhealthy Condition: (HER2)-positive breast cancer Age Group: 50 years (range: 30–78 years) Sex: F Population Size: 5 Sources: |
Dry skin | all grades, 10% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Insomnia | all grades, 10% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Back pain | all grades, 11% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Dyspepsia | all grades, 11% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Dyspnea | all grades, 12% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Pain in extremity | all grades, 12% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Stomatitis | all grades, 14% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Mucosal inflammation | all grades, 15% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Vomiting | all grades, 26% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Rash | all grades, 28% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Nausea | all grades, 44% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Palmar-plantar erythrodysesthesia syndrome | all grades, 53% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Diarrhea | all grades, 65% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
ALT increased | grade 1-2, 35% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Bilirubin total increased | grade 1-2, 41% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
AST increased | grade 1-2, 46% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Back pain | grade 3, 1% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Pain in extremity | grade 3, 1% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Palmar-plantar erythrodysesthesia syndrome | grade 3, 12% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Diarrhea | grade 3, 13% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
ALT increased | grade 3, 2% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
AST increased | grade 3, 2% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Nausea | grade 3, 2% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Rash | grade 3, 2% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Vomiting | grade 3, 2% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Dyspnea | grade 3, 3% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Bilirubin total increased | grade 3, 4% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Dermatitis acneiform | grade 3, <1% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Dyspepsia | grade 3, <1% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Insomnia | grade 3, <1% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Diarrhea | grade 4, 1% Disc. AE |
1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
AST increased | grade 4, <1% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Hepatotoxicity | severe|grade 5 | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: capecitabine(2000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle) Sources: |
unhealthy, 53 years n = 198 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 53 years Sex: F Population Size: 198 Sources: |
Lymphocyte count decreased | grade 1, 1 patient | 1800 mg 1 times / day steady, oral MTD Dose: 1800 mg, 1 times / day Route: oral Route: steady Dose: 1800 mg, 1 times / day Sources: |
unhealthy, 60 years (range: 37 – 73 years) n = 6 Health Status: unhealthy Condition: Solid Tumors Age Group: 60 years (range: 37 – 73 years) Sex: M+F Population Size: 6 Sources: |
Paronychia | grade 1, 1 patient | 1800 mg 1 times / day steady, oral MTD Dose: 1800 mg, 1 times / day Route: oral Route: steady Dose: 1800 mg, 1 times / day Sources: |
unhealthy, 60 years (range: 37 – 73 years) n = 6 Health Status: unhealthy Condition: Solid Tumors Age Group: 60 years (range: 37 – 73 years) Sex: M+F Population Size: 6 Sources: |
Seborrheic dermatitis | grade 1, 1 patient | 1800 mg 1 times / day steady, oral MTD Dose: 1800 mg, 1 times / day Route: oral Route: steady Dose: 1800 mg, 1 times / day Sources: |
unhealthy, 60 years (range: 37 – 73 years) n = 6 Health Status: unhealthy Condition: Solid Tumors Age Group: 60 years (range: 37 – 73 years) Sex: M+F Population Size: 6 Sources: |
Stomatitis | grade 1, 1 patient | 1800 mg 1 times / day steady, oral MTD Dose: 1800 mg, 1 times / day Route: oral Route: steady Dose: 1800 mg, 1 times / day Sources: |
unhealthy, 60 years (range: 37 – 73 years) n = 6 Health Status: unhealthy Condition: Solid Tumors Age Group: 60 years (range: 37 – 73 years) Sex: M+F Population Size: 6 Sources: |
Anorexia | grade 1, 3 patients | 1800 mg 1 times / day steady, oral MTD Dose: 1800 mg, 1 times / day Route: oral Route: steady Dose: 1800 mg, 1 times / day Sources: |
unhealthy, 60 years (range: 37 – 73 years) n = 6 Health Status: unhealthy Condition: Solid Tumors Age Group: 60 years (range: 37 – 73 years) Sex: M+F Population Size: 6 Sources: |
Rash | grade 2, 2 patients | 1800 mg 1 times / day steady, oral MTD Dose: 1800 mg, 1 times / day Route: oral Route: steady Dose: 1800 mg, 1 times / day Sources: |
unhealthy, 60 years (range: 37 – 73 years) n = 6 Health Status: unhealthy Condition: Solid Tumors Age Group: 60 years (range: 37 – 73 years) Sex: M+F Population Size: 6 Sources: |
Gamma GT increased | grade 3, 1 patient DLT |
1800 mg 1 times / day steady, oral MTD Dose: 1800 mg, 1 times / day Route: oral Route: steady Dose: 1800 mg, 1 times / day Sources: |
unhealthy, 60 years (range: 37 – 73 years) n = 6 Health Status: unhealthy Condition: Solid Tumors Age Group: 60 years (range: 37 – 73 years) Sex: M+F Population Size: 6 Sources: |
Diarrhea | grade 3, 2 patients DLT, Disc. AE |
1800 mg 1 times / day steady, oral MTD Dose: 1800 mg, 1 times / day Route: oral Route: steady Dose: 1800 mg, 1 times / day Sources: |
unhealthy, 60 years (range: 37 – 73 years) n = 6 Health Status: unhealthy Condition: Solid Tumors Age Group: 60 years (range: 37 – 73 years) Sex: M+F Population Size: 6 Sources: |
Bilirubin total increased | grade 1-2, 20% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: Letrozole(2.5 mg/day) Sources: |
unhealthy, 63 years n = 111 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 63 years Sex: F Population Size: 111 Sources: |
ALT increased | grade 1-2, 40% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: Letrozole(2.5 mg/day) Sources: |
unhealthy, 63 years n = 111 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 63 years Sex: F Population Size: 111 Sources: |
AST increased | grade 1-2, 47% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: Letrozole(2.5 mg/day) Sources: |
unhealthy, 63 years n = 111 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 63 years Sex: F Population Size: 111 Sources: |
ALT increased | grade 3, 5% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: Letrozole(2.5 mg/day) Sources: |
unhealthy, 63 years n = 111 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 63 years Sex: F Population Size: 111 Sources: |
AST increased | grade 3, 6% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: Letrozole(2.5 mg/day) Sources: |
unhealthy, 63 years n = 111 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 63 years Sex: F Population Size: 111 Sources: |
Bilirubin total increased | grade 3, <1% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: Letrozole(2.5 mg/day) Sources: |
unhealthy, 63 years n = 111 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 63 years Sex: F Population Size: 111 Sources: |
ALT increased | grade 4, <1% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: Letrozole(2.5 mg/day) Sources: |
unhealthy, 63 years n = 111 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 63 years Sex: F Population Size: 111 Sources: |
Bilirubin total increased | grade 4, <1% | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: Letrozole(2.5 mg/day) Sources: |
unhealthy, 63 years n = 111 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 63 years Sex: F Population Size: 111 Sources: |
Hepatotoxicity | severe|grade 5 | 1250 mg 1 times / day steady, oral Recommended Dose: 1250 mg, 1 times / day Route: oral Route: steady Dose: 1250 mg, 1 times / day Co-administed with:: Letrozole(2.5 mg/day) Sources: |
unhealthy, 63 years n = 111 Health Status: unhealthy Condition: stage IV breast cancer | estrogen receptor+ |progesterone receptor+ Age Group: 63 years Sex: F Population Size: 111 Sources: |
Overview
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
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Drug as perpetrator
Drug as victim
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
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PubMed
Title | Date | PubMed |
---|---|---|
Gateways to clinical trials. | 2003 Oct |
|
Effects of the EGFR/HER2 kinase inhibitor GW572016 on EGFR- and HER2-overexpressing breast cancer cell line proliferation, radiosensitization, and resistance. | 2004 Feb 1 |
|
Truncated ErbB2 receptor (p95ErbB2) is regulated by heregulin through heterodimer formation with ErbB3 yet remains sensitive to the dual EGFR/ErbB2 kinase inhibitor GW572016. | 2004 Jan 22 |
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Gateways to clinical trials. | 2004 Jan-Feb |
|
The epidermal growth factor receptor as a target for colorectal cancer therapy. | 2005 Feb |
|
Gateways to clinical trials. | 2005 Jan-Feb |
|
Clinical trials of intracellular signal transductions inhibitors for breast cancer--a strategy to overcome endocrine resistance. | 2005 Jul |
|
Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. | 2005 Mar |
|
Lessons from the drug discovery of lapatinib, a dual ErbB1/2 tyrosine kinase inhibitor. | 2006 |
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Gateways to clinical trials. | 2006 Dec |
|
Targeted therapy for metastatic breast cancer. | 2006 Dec 28 |
|
Lapatinib plus capecitabine for HER2-positive advanced breast cancer. | 2006 Dec 28 |
|
A novel mutation in the tyrosine kinase domain of ERBB2 in hepatocellular carcinoma. | 2006 Dec 6 |
|
Determination of lapatinib (GW572016) in human plasma by liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS). | 2006 Feb 2 |
|
Gateways to clinical trials. | 2006 Jan-Feb |
|
[Molecular-targeted agents in breast cancer]. | 2006 Jun |
|
Closing in on a cure. | 2006 Oct 23 |
|
Combination therapy with aromatase inhibitors: the next era of breast cancer treatment? | 2006 Sep 18 |
|
HER2 therapy. HER2 (ERBB2): functional diversity from structurally conserved building blocks. | 2007 |
|
relocating job wise? A mathematical model separates quantitatively the cytostatic and cytotoxic effects of a HER2 tyrosine kinase inhibitor. | 2007 Apr 3 |
|
Lapatinib plus capecitabine in breast cancer. | 2007 Apr 5 |
|
TEACH: Tykerb evaluation after chemotherapy. | 2007 Feb |
|
Lapatinib induces apoptosis in trastuzumab-resistant breast cancer cells: effects on insulin-like growth factor I signaling. | 2007 Feb |
|
Recent advances in the therapy of renal cancer. | 2007 Feb |
|
Synergistic inhibition of breast cancer cell lines with a dual inhibitor of EGFR-HER-2/neu and a Bcl-2 inhibitor. | 2007 Feb |
|
Therapeutic advances in the treatment of brain metastases. | 2007 Jan |
|
Proteomic identification of secreted proteins as surrogate markers for signal transduction inhibitor activity. | 2007 Jan 29 |
|
Gateways to clinical trials. | 2007 Jan-Feb |
|
Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. | 2007 Mar |
Patents
Sample Use Guides
The recommended dosage of TYKERB for advanced or metastatic breast cancer is 1,250 mg (5 tablets) given orally once daily on Days 1-21 continuously in combination with capecitabine 2,000 mg/m2 /day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle. The recommended dose of TYKERB for hormone receptor positive, HER2 positive metastatic breast cancer is 1500 mg (6 tablets) given orally once daily continuously in combination with letrozole. When TYKERB is coadministered with letrozole, the recommended dose of letrozole is 2.5 mg once daily. • TYKERB should be taken at least one hour before or one hour after a meal. However, capecitabine should be taken with food or within 30 minutes after food. • TYKERB should be taken once daily. Do not divide daily doses of TYKERB. • Modify dose for cardiac and other toxicities, severe hepatic impairment, and CYP3A4 drug interactions.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22964224
lapatinib-induced time- and dose-dependent phosphorylation dynamics in SKBR3 breast cancer cells. Among 4953 identified phosphopeptides from 1548 proteins, a small proportion (5-7%) was regulated at least twofold by 1-10 μm lapatinib.
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FDA ORPHAN DRUG |
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ACTIVE MOIETY
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