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Details

Stereochemistry ACHIRAL
Molecular Formula C21H15ClF4N4O3
Molecular Weight 482.8161
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of REGORAFENIB

SMILES

CNC(=O)c1cc(ccn1)Oc2ccc(c(c2)F)NC(=Nc3ccc(c(c3)C(F)(F)F)Cl)O

InChI

InChIKey=FNHKPVJBJVTLMP-UHFFFAOYSA-N
InChI=1S/C21H15ClF4N4O3/c1-27-19(31)18-10-13(6-7-28-18)33-12-3-5-17(16(23)9-12)30-20(32)29-11-2-4-15(22)14(8-11)21(24,25)26/h2-10H,1H3,(H,27,31)(H2,29,30,32)

HIDE SMILES / InChI

Molecular Formula C21H15ClF4N4O3
Molecular Weight 482.8161
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: description was created based on several sources, including http://www.news-medical.net/news/20140220/Bayer-enrolls-patients-for-Phase-III-trial-of-Stivarga-(regorafenib)-tablets-in-colorectal-cancer.aspx; http://www.ncbi.nlm.nih.gov/pubmed/?term=21170960

Regorafenib (trade name Stivarga) is an orally bioavailable small molecule with potential antiangiogenic and antineoplastic activities. Regorafenib binds to and inhibits vascular endothelial growth factor receptors (VEGFRs) 2 and 3, and Ret, Kit, PDGFR and Raf kinases, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation. VEGFRs are receptor tyrosine kinases that play important roles in tumor angiogenesis; the receptor tyrosine kinases RET, KIT, and PDGFR, and the serine/threonine-specific Raf kinase are involved in tumor cell signaling. In in vivo models, regorafenib demonstrated anti-angiogenic activity in a rat tumor model, and inhibition of tumor growth as well as anti-metastatic activity in several mouse xenograft models including some for human colorectal carcinoma. Since 2009 it was studied as a potential treatment option in multiple tumor types. Stivarga is approved by FDA to treat two different tumor types: metastatic colorectal cancer in patients who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy (approved in 2012) and to treat patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor who have been previously treated with imatinib mesylate and sunitinib malate (approved in 2013).

CNS Activity

Curator's Comment:: In a single dose distribution study in pregnant rats, there was increased penetration of regorafenib across the blood-brain barrier in fetuses compared to dams.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P04049
Gene ID: 5894.0
Gene Symbol: RAF1
Target Organism: Homo sapiens (Human)
2.5 nM [IC50]
Target ID: P07949
Gene ID: 5979.0
Gene Symbol: RET
Target Organism: Homo sapiens (Human)
1.5 nM [IC50]
Target ID: P35968
Gene ID: 3791.0
Gene Symbol: KDR
Target Organism: Homo sapiens (Human)
4.2 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
STIVARGA

Approved Use

Indicated for the treatment of patients with: metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy; locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.

Launch Date

1.34870401E12
Secondary
STIVARGA

Approved Use

Indicated for the treatment of patients with: metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy; locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.

Launch Date

1.34870401E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2522.2 μg/L
160 mg 1 times / day steady-state, oral
dose: 160 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
REGORAFENIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
33042.8 μg × h/mL
160 mg 1 times / day steady-state, oral
dose: 160 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
REGORAFENIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
30.4 h
160 mg 1 times / day steady-state, oral
dose: 160 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
REGORAFENIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.5%
REGORAFENIB plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
160 mg 1 times / day multiple, oral
Recommended
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources:
Disc. AE: Hepatic failure...
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.47
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.47
Disc. AE: General physical health deterioration, Palmar-plantar erythrodysaesth....
AEs leading to
discontinuation/dose reduction:
General physical health deterioration (4%)
Palmar-plantar erythrodysaesth. (1%)
Decreased appetite (1%)
Pneumonia (1%)
Rash (1%)
Sources: Page: 203085Orig1s000MedR.pdf - p.47
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.48
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.48
Disc. AE: Palmar-plantar erythrodysaesth., Diarrhea...
AEs leading to
discontinuation/dose reduction:
Palmar-plantar erythrodysaesth. (18.2%)
Diarrhea (3.8%)
Hypertension (3.2%)
Fatigue (2%)
Rash (2%)
Mucositis (1.2%)
Abdominal pain (1%)
Asthenia (1%)
Sources: Page: 203085Orig1s000MedR.pdf - p.48
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.49
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.49
Disc. AE: Palmar-plantar erythrodysaesth., Diarrhea...
AEs leading to
discontinuation/dose reduction:
Palmar-plantar erythrodysaesth. (18.8%)
Diarrhea (6.2%)
Pyrexia (4.6%)
Fatigue (4%)
Rash (3.6%)
Hyperbilirubinemia (3.6%)
Decreased appetite (3%)
Asthenia (2.8%)
Hypertension (2.6%)
Abdominal pain (2.4%)
Stomatitis (2.2%)
Dyspnea (2%)
AST increased (1.8%)
Vomiting (1.8%)
Thrombocytopenia (1.6%)
ALT increased (1.4%)
Proteinuria (1.2%)
Sources: Page: 203085Orig1s000MedR.pdf - p.49
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.53
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.53
Other AEs: Hemorrhage, Hemorrhage...
Other AEs:
Hemorrhage (grade 1, 17.4%)
Hemorrhage (grade 2, 1.8%)
Hemorrhage (grade 3, 1.4%)
Hemorrhage (grade 5, 0.8%)
Sources: Page: 203085Orig1s000MedR.pdf - p.53
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.54
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.54
Other AEs: Palmar-plantar erythrodysaesth., Rash...
Other AEs:
Palmar-plantar erythrodysaesth. (grade 3, 17%)
Rash (grade 3, 5%)
Sources: Page: 203085Orig1s000MedR.pdf - p.54
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.57
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.57
Other AEs: Pulmonary embolism, Venous thromboembolism...
Other AEs:
Pulmonary embolism (grade 3, 0.8%)
Venous thromboembolism (grade 3, 0.6%)
Arterial thromboembolism (grade 3, 1%)
Sources: Page: 203085Orig1s000MedR.pdf - p.57
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.59
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.59
Other AEs: Decreased appetite, Diarrhea...
Other AEs:
Decreased appetite (grade 3, 5%)
Diarrhea (grade 3, 8%)
Mucositis (grade 3, 4%)
Weight loss (grade 3, <1%)
Infection (grade 3, 9%)
Hypertension (grade 3, 8%)
Pain (grade 3, 3%)
Fever (grade 3, 2%)
Rash (grade 3, 6%)
Hemorrhage (grade 3, 2%)
Headache (grade 3, <1%)
Asthenia (grade 3, 15%)
Sources: Page: 203085Orig1s000MedR.pdf - p.59
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Other AEs: Dysphonia, Dry mouth...
Other AEs:
Dysphonia
Dry mouth
Decreased appetite
Voice alteration (75%)
Hand and foot skin reaction (58%)
Mucositis (67%)
Diarrhea (58%)
Hypertension (42%)
Fatigue (58%)
Anorexia (42%)
Rash (25%)
Alopecia (25%)
Voice alteration (grade 3, 8%)
Hand and foot skin reaction (grade 3, 42%)
Diarrhea (grade 3, 8%)
Hypertension (grade 3, 25%)
Fatigue (grade 3, 8%)
Rash (grade 3, 8%)
Sources:
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Other AEs: Voice alteration, Hand and foot skin reaction...
Other AEs:
Voice alteration (42%)
Hand and foot skin reaction (67%)
Mucositis (25%)
Diarrhea (50%)
Hypertension (50%)
Fatigue (17%)
Anorexia (50%)
Rash (50%)
Alopecia (33%)
Hand and foot skin reaction (grade 3, 25%)
Mucositis (grade 3, 8%)
Diarrhea (grade 3, 17%)
Hypertension (grade 3, 17%)
Anorexia (grade 3, 8%)
Rash (grade 3, 8%)
Sources:
120 mg 1 times / day multiple, oral
Studied dose
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 8
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 8
Sources:
DLT: Infection, Hand and foot skin reaction...
Dose limiting toxicities:
Infection (25%)
Hand and foot skin reaction (13%)
Sources:
160 mg 1 times / day multiple, oral
Studied dose
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
DLT: Allergic reaction, Vomiting...
Dose limiting toxicities:
Allergic reaction (8%)
Vomiting (8%)
Sources:
220 mg 1 times / day multiple, oral
Studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
DLT: Hand and foot skin reaction, Pruritic rash...
Dose limiting toxicities:
Hand and foot skin reaction (17%)
Pruritic rash (8%)
Abdominal pain (8%)
Asthma bronchial (8%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Hepatic failure grade 5, 1.6%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources:
Decreased appetite 1%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.47
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.47
Palmar-plantar erythrodysaesth. 1%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.47
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.47
Pneumonia 1%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.47
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.47
Rash 1%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.47
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.47
General physical health deterioration 4%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.47
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.47
Abdominal pain 1%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.48
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.48
Asthenia 1%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.48
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.48
Mucositis 1.2%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.48
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.48
Palmar-plantar erythrodysaesth. 18.2%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.48
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.48
Fatigue 2%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.48
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.48
Rash 2%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.48
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.48
Hypertension 3.2%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.48
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.48
Diarrhea 3.8%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.48
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.48
Proteinuria 1.2%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.49
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.49
ALT increased 1.4%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.49
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.49
Thrombocytopenia 1.6%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.49
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.49
AST increased 1.8%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.49
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.49
Vomiting 1.8%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.49
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.49
Palmar-plantar erythrodysaesth. 18.8%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.49
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.49
Dyspnea 2%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.49
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.49
Stomatitis 2.2%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.49
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.49
Abdominal pain 2.4%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.49
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.49
Hypertension 2.6%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.49
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.49
Asthenia 2.8%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.49
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.49
Decreased appetite 3%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.49
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.49
Hyperbilirubinemia 3.6%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.49
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.49
Rash 3.6%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.49
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.49
Fatigue 4%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.49
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.49
Pyrexia 4.6%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.49
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.49
Diarrhea 6.2%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.49
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.49
Hemorrhage grade 1, 17.4%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.53
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.53
Hemorrhage grade 2, 1.8%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.53
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.53
Hemorrhage grade 3, 1.4%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.53
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.53
Hemorrhage grade 5, 0.8%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.53
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.53
Palmar-plantar erythrodysaesth. grade 3, 17%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.54
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.54
Rash grade 3, 5%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.54
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.54
Venous thromboembolism grade 3, 0.6%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.57
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.57
Pulmonary embolism grade 3, 0.8%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.57
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.57
Arterial thromboembolism grade 3, 1%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.57
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.57
Asthenia grade 3, 15%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.59
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.59
Fever grade 3, 2%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.59
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.59
Hemorrhage grade 3, 2%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.59
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.59
Pain grade 3, 3%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.59
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.59
Mucositis grade 3, 4%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.59
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.59
Decreased appetite grade 3, 5%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.59
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.59
Rash grade 3, 6%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.59
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.59
Diarrhea grade 3, 8%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.59
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.59
Hypertension grade 3, 8%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.59
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.59
Infection grade 3, 9%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.59
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.59
Headache grade 3, <1%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.59
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.59
Weight loss grade 3, <1%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources: Page: 203085Orig1s000MedR.pdf - p.59
unhealthy, 22 to 82 years
n = 500
Health Status: unhealthy
Condition: colorectal cancer
Age Group: 22 to 82 years
Sex: M+F
Population Size: 500
Sources: Page: 203085Orig1s000MedR.pdf - p.59
Decreased appetite
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Dry mouth
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Dysphonia
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Alopecia 25%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Rash 25%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Anorexia 42%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Hypertension 42%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Diarrhea 58%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Fatigue 58%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Hand and foot skin reaction 58%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Mucositis 67%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Voice alteration 75%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Hypertension grade 3, 25%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Hand and foot skin reaction grade 3, 42%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Diarrhea grade 3, 8%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Fatigue grade 3, 8%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Rash grade 3, 8%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Voice alteration grade 3, 8%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Fatigue 17%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Mucositis 25%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Alopecia 33%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Voice alteration 42%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Anorexia 50%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Diarrhea 50%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Hypertension 50%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Rash 50%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Hand and foot skin reaction 67%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Diarrhea grade 3, 17%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Hypertension grade 3, 17%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Hand and foot skin reaction grade 3, 25%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Anorexia grade 3, 8%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Mucositis grade 3, 8%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Rash grade 3, 8%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Hand and foot skin reaction 13%
DLT
120 mg 1 times / day multiple, oral
Studied dose
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 8
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 8
Sources:
Infection 25%
DLT
120 mg 1 times / day multiple, oral
Studied dose
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 8
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 8
Sources:
Allergic reaction 8%
DLT
160 mg 1 times / day multiple, oral
Studied dose
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Vomiting 8%
DLT
160 mg 1 times / day multiple, oral
Studied dose
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Hand and foot skin reaction 17%
DLT
220 mg 1 times / day multiple, oral
Studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Abdominal pain 8%
DLT
220 mg 1 times / day multiple, oral
Studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Asthma bronchial 8%
DLT
220 mg 1 times / day multiple, oral
Studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
Pruritic rash 8%
DLT
220 mg 1 times / day multiple, oral
Studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
n = 12
Health Status: unhealthy
Condition: solid tumors
Age Group: median age 60 years
Sex: M+F
Population Size: 12
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
yes [IC50 44.7 uM]
yes [Ki 0.6 uM]
unknown
Comment: The effect of regorafenib on the PK of CYP2C8, CYP2C9, CYP2C19 and CYP3A4 probe substrates are being evaluated in an ongoing study.
Page: -
yes [Ki 11.1 uM]
unknown
Comment: The effect of regorafenib on the PK of CYP2C8, CYP2C9, CYP2C19 and CYP3A4 probe substrates are being evaluated in an ongoing study.
Page: -
yes [Ki 16.4 uM]
unknown
Comment: Acts via metabolite M2. The effect of regorafenib on the PK of CYP2C8, CYP2C9, CYP2C19 and CYP3A4 probe substrates are being evaluated in an ongoing study.
Page: -
yes [Ki 2.1 uM]
yes [Ki 3 uM]
yes [Ki 4.7 uM]
unknown
Comment: The effect of regorafenib on the PK of CYP2C8, CYP2C9, CYP2C19 and CYP3A4 probe substrates are being evaluated in an ongoing study.
Page: -
yes [Ki 7.8 uM]
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
major
yes (co-administration study)
Comment: The administration of ketoconazole 400 mg daily for 18 days with a single 160 mg dose of regorafenib increased the mean AUC of regorafenib by 33% and decreased the mean AUC of M2 and M5 each by 93%. The administration of rifampin 600 mg daily for 9 days with a single 160 mg dose of regorafenib decreased the mean AUC of regorafenib by 50% and increased the mean AUC of M5 by 264%; the mean AUC of M2 was similar with and without rifampin.
Page: -
no
no
no
no
yes
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity.
2011 Jul 1
Small molecule inhibitors of BRAF in clinical trials.
2012 Jan 15
Regorafenib impairs mitochondrial functions, activates AMP-activated protein kinase, induces autophagy, and causes rat hepatocyte necrosis.
2015 Jan 2
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
2015 May 18
Patents

Sample Use Guides

160 mg Stivarga orally, once daily for the first 21 days of each 28-day cycle. Take with a low-fat meal.
Route of Administration: Oral
For the migration inhibition assay, human lymphatic endothelial cells (LECs) were grown overnight on a gelatin-coated six-well plate, serum starved for 6 hr in EBM-2 media containing 0.1% BSA and treated with 100 nmol/L regorafenib for 1 hr. Regorafenib inhibited the proliferation of 19 cell lines derived from human colon cancers, with IC50 values ranging from 2.6 to 10 umol/L.
Substance Class Chemical
Created
by admin
on Sat Jun 26 13:23:20 UTC 2021
Edited
by admin
on Sat Jun 26 13:23:20 UTC 2021
Record UNII
24T2A1DOYB
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
REGORAFENIB
DASH   INN   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
BAY 73-4506 MONOHYDRATE
Code English
4-(4-(((4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL)CARBAMOYL)AMINO)-3-FLUOROPHENOXY)-N-METHYLPYRIDINE-2-CARBOXAMIDE
Systematic Name English
REGORAFENIB [WHO-DD]
Common Name English
BAY 73-4506
Code English
BAY-734506
Code English
REGORAFENIB [VANDF]
Common Name English
REGORAFENIB [USP-RS]
Common Name English
REGORAFENIB [INN]
Common Name English
STIVARGA
Brand Name English
REGORAFENIB [USAN]
Common Name English
REGORAFENIB [MI]
Common Name English
REGORAFENIB [ORANGE BOOK]
Common Name English
BAY-73-4506
Code English
Classification Tree Code System Code
NCI_THESAURUS C1742
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
WHO-ATC L01XE21
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
FDA ORPHAN DRUG 329410
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
NCI_THESAURUS C1404
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
FDA ORPHAN DRUG 690619
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
LIVERTOX 839
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
EMA ASSESSMENT REPORTS STIVARGA (AUTHORIZED: COLORECTAL NEOPLASMS)
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
NDF-RT N0000175605
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
WHO-VATC QL01XE21
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
FDA ORPHAN DRUG 478015
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
Code System Code Type Description
WIKIPEDIA
Regorafenib
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
PRIMARY
CAS
755037-03-7
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
PRIMARY
IUPHAR
5891
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
PRIMARY
DRUG BANK
DB08896
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
PRIMARY
FDA UNII
24T2A1DOYB
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
PRIMARY
LACTMED
Regorafenib
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
PRIMARY
DRUG CENTRAL
4654
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
PRIMARY
EVMPD
SUB73090
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
PRIMARY
NCI_THESAURUS
C78204
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
PRIMARY
PUBCHEM
11167602
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
PRIMARY
RXCUI
1312397
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
PRIMARY RxNorm
ChEMBL
CHEMBL1946170
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
PRIMARY
MERCK INDEX
M11701
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
PRIMARY
EPA CompTox
755037-03-7
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
PRIMARY
MESH
C559147
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
PRIMARY
NDF-RT
N0000185504
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
PRIMARY Cytochrome P450 2C9 Inhibitors [MoA]
INN
9026
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
PRIMARY
USP_CATALOG
1600201
Created by admin on Sat Jun 26 13:23:21 UTC 2021 , Edited by admin on Sat Jun 26 13:23:21 UTC 2021
PRIMARY USP-RS
Related Record Type Details
METABOLIC ENZYME -> INHIBITOR
Ki
TARGET -> INHIBITOR
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> INHIBITOR
SN-38 is metabolized by UGT1A1, it appears that regorafenib inhibits UGT1A1 in humans. The mean AUC of irinotecan and SN-38 increased by 28% and 44%, respectively, when irinotecan was administered five days after the last of seven daily doses of regorafenib.
TRANSPORTER -> INHIBITOR
Regorafenib inhibits BCRP in vitro.
IC50
TRANSPORTER -> INHIBITOR
Regorafenib inhibits Pgp and BCRP in vitro.
METABOLIC ENZYME -> SUBSTRATE
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> INHIBITOR
Ki
TARGET -> INHIBITOR
TARGET -> INHIBITOR
METABOLIC ENZYME -> INHIBITOR
Ki
METABOLIC ENZYME -> INHIBITOR
Ki
METABOLIC ENZYME -> INHIBITOR
Ki
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
TARGET -> INHIBITOR
EXCRETED UNCHANGED
FECAL
SALT/SOLVATE -> PARENT
Related Record Type Details
METABOLITE INACTIVE -> PARENT
URINE
METABOLITE INACTIVE -> PARENT
METABOLITE ACTIVE -> PARENT
AT STEADY STATE
MAJOR
PLASMA
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC SINGLE DOSE

Cmax PHARMACOKINETIC
Tmax PHARMACOKINETIC SINGLE DOSE