Trial Outcomes & Findings for Sorafenib Dose Escalation in Renal Cell Carcinoma (NCT NCT00618982)

Last Updated: 2015-12-24

Results Overview

Best Response (Response Rate) of a subject was defined as the proportion of patients with confirmed Complete Response (CR) or Partial Response (PR) as their best response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed CR was defined as disappearance of tumor and PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

83 participants

Primary outcome timeframe

Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.

Results posted on

2015-12-24

Participant Flow

Subjects were enrolled from 04 Feb to 05 Nov 2008 at 19 centers in 5 countries (Germany, France, United Kingdom, Italy and Poland).

Of the 89 subjects enrolled, 83 were treated with the study drug. Safety population = 83 subjects who took at least one dose of study drug and had any data after baseline. Intent to treat population = 67 subjects treated with the study drug who had at least one efficacy evaluation after baseline.

Participant milestones

Participant milestones
Measure	Sorafenib (Nexavar, BAY43-9006) Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle, 600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed.
Overall Study STARTED	83
Overall Study COMPLETED	33
Overall Study NOT COMPLETED	50

Reasons for withdrawal

Reasons for withdrawal
Measure	Sorafenib (Nexavar, BAY43-9006) Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle, 600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed.
Overall Study Adverse Event	23
Overall Study Withdrawal by Subject	1
Overall Study Protocol Violation	1
Overall Study ongoing, still treated with study med.	25

Baseline Characteristics

Sorafenib Dose Escalation in Renal Cell Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sorafenib (Nexavar, BAY43-9006) n=83 Participants Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle, 600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed.
Age, Continuous	61 years n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants
Sex: Female, Male Male	54 Participants n=5 Participants
ECOG (Eastern Cooperative Oncology Group) Performance Status 0	49 participants n=5 Participants
ECOG (Eastern Cooperative Oncology Group) Performance Status 1	34 participants n=5 Participants
Stage at study entry Stage III	1 participants n=5 Participants
Stage at study entry Stage IV	82 participants n=5 Participants

PRIMARY outcome

Timeframe: Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.

Population: The population for the analysis of primary efficacy variable was the modified intent-to-treat (mITT) population defined as the patients treated for at least 6 months with 4 months at their highest tolerated dose.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=18 Participants Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle, 600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed.	Sorafenib (Nexavar, BAY43-9006)_600 mg Participants received 600 mg orally twice daily (bid)	Sorafenib (Nexavar, BAY43-9006)_800 mg Participants received 800 mg orally twice daily (bid)
Best Response - mITT (Modified Intent-to-treat) Population	8 Participants Interval 21.5 to 69.2	—	—

PRIMARY outcome

Population: The population for the efficacy analysis was the intent-to-treat (ITT) population defined as all patients who received at least one dose of study medication with at least one valid tumor assessment post-baseline.

Tumor Response of a subject was defined as the best tumor response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed Complete Response (CR) was defined as disappearance of tumor, Partial Response (PR) was defined as a decrease of at least 30% in the sum of target lesions, Stable Disease (SD) was defined as steady state of disease, and Progressive Disease (PD) was defined as at least a 20% increase in the sum of measured lesions or appearance of new lesions.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=67 Participants Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle, 600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed.	Sorafenib (Nexavar, BAY43-9006)_600 mg Participants received 600 mg orally twice daily (bid)	Sorafenib (Nexavar, BAY43-9006)_800 mg Participants received 800 mg orally twice daily (bid)
Tumor Response - ITT (Intent to Treat) Population Complete Response (CR)	0 participants	—	—
Tumor Response - ITT (Intent to Treat) Population Partial Response (PR)	12 participants	—	—
Tumor Response - ITT (Intent to Treat) Population Stable Disease (SD)	46 participants	—	—
Tumor Response - ITT (Intent to Treat) Population Progressive Disease (PD)	9 participants	—	—

SECONDARY outcome

Timeframe: Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8 and 10 hours post-dose.

Population: PK Analysis Population. 40 participants in the 400 mg bid group that had an AUC(0-10)ss calculated; 30 participants in the 600 mg bid group that had an AUC(0-10)ss calculated; 26 participants and 27 participants in the 800 mg bid group that had an AUC(0-10)ss calculated, for sorafenib and M2 parameter respectively.

AUC(0-10),ss was defined as an area under the plasma concentration versus time curve from time zero to 10 hours post-dose. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=40 Participants Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle, 600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed.	Sorafenib (Nexavar, BAY43-9006)_600 mg n=30 Participants Participants received 600 mg orally twice daily (bid)	Sorafenib (Nexavar, BAY43-9006)_800 mg n=26 Participants Participants received 800 mg orally twice daily (bid)
Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 10 Hours Postdose (AUC(0-10),ss) Sorafenib (N=40, 30, 26)	50.0 mg*h/L Geometric Coefficient of Variation 39.2	51.2 mg*h/L Geometric Coefficient of Variation 43.7	43.8 mg*h/L Geometric Coefficient of Variation 47.8
Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 10 Hours Postdose (AUC(0-10),ss) M2 (BAY67-3472) (N=40, 30, 27)	8.80 mg*h/L Geometric Coefficient of Variation 74.3	10.4 mg*h/L Geometric Coefficient of Variation 82.1	8.23 mg*h/L Geometric Coefficient of Variation 87.2

SECONDARY outcome

Population: PK Analysis Population. 32 participants in the 400 mg bid group that had an AUC(0-12)ss calculated; 23 participants in the 600 mg bid group that had an AUC(0-12)ss calculated; 19 participants and 20 participants in the 800 mg bid group that had an AUC(0-12)ss calculated, for sorafenib and M2 parameter respectively.

AUC(0-12),ss was defined as an area under the plasma concentration versus time curve from time zero to 12 hours post-dose. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=32 Participants Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle, 600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed.	Sorafenib (Nexavar, BAY43-9006)_600 mg n=23 Participants Participants received 600 mg orally twice daily (bid)	Sorafenib (Nexavar, BAY43-9006)_800 mg n=19 Participants Participants received 800 mg orally twice daily (bid)
Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 12 Hours Postdose (AUC(0-12),ss) M2 (BAY67-3472) (N=32, 23, 20)	9.58 mg*h/L Geometric Coefficient of Variation 78.2	11.2 mg*h/L Geometric Coefficient of Variation 75.9	8.41 mg*h/L Geometric Coefficient of Variation 94.6
Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 12 Hours Postdose (AUC(0-12),ss) Sorafenib (N=32, 23, 19)	57.2 mg*h/L Geometric Coefficient of Variation 39.1	57.6 mg*h/L Geometric Coefficient of Variation 46.1	47.0 mg*h/L Geometric Coefficient of Variation 51.9

SECONDARY outcome

Population: PK Analysis Population. 40 participants in the 400 mg bid group that had Cmax calculated; 31 participants in the 600 mg bid group that had Cmax calculated; 28 participants in the 800 mg bid group that had Cmax calculated.

Cmax was defined as a maximum plasma concentration at steady-state. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=40 Participants Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle, 600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed.	Sorafenib (Nexavar, BAY43-9006)_600 mg n=31 Participants Participants received 600 mg orally twice daily (bid)	Sorafenib (Nexavar, BAY43-9006)_800 mg n=28 Participants Participants received 800 mg orally twice daily (bid)
Pharmacokinetics (PK) Analysis - Maximum Observed Concentration in Plasma (Cmax) Sorafenib	7.53 mg/L Geometric Coefficient of Variation 38.0	7.62 mg/L Geometric Coefficient of Variation 39.3	6.64 mg/L Geometric Coefficient of Variation 42.1
Pharmacokinetics (PK) Analysis - Maximum Observed Concentration in Plasma (Cmax) M2 (BAY67-3472)	1.31 mg/L Geometric Coefficient of Variation 80.8	1.51 mg/L Geometric Coefficient of Variation 81.4	1.30 mg/L Geometric Coefficient of Variation 88.5

SECONDARY outcome

Population: PK Analysis Population. 40 participants in the 400 mg bid group that had Tmax calculated; 31 participants in the 600 mg bid group that had Tmax calculated; 28 participants in the 800 mg bid group that had Tmax calculated.

Tmax was defined as a time to maximum concentration at steady-state. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=40 Participants Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle, 600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed.	Sorafenib (Nexavar, BAY43-9006)_600 mg n=31 Participants Participants received 600 mg orally twice daily (bid)	Sorafenib (Nexavar, BAY43-9006)_800 mg n=28 Participants Participants received 800 mg orally twice daily (bid)
Pharmacokinetics (PK) Analysis - Time to Maximum Concentration (Tmax) Sorafenib	2 hours Interval 0.0 to 12.0	2 hours Interval 0.0 to 12.0	2 hours Interval 0.0 to 12.0
Pharmacokinetics (PK) Analysis - Time to Maximum Concentration (Tmax) M2 (BAY67-3472)	2 hours Interval 0.0 to 10.3	2 hours Interval 0.0 to 12.0	1 hours Interval 0.0 to 12.0

SECONDARY outcome

Population: Intent-to-treat (ITT).

Progression-free survival (PFS) was defined as the time from start of study medication to the first documented disease progression per RECIST (by independent radiological assessment) or clinical progression as per investigator assessment or death due to any cause whichever occurred first. For patients who had not recurred or died at the time of analysis, PFS was censored at their last date of evaluable scan.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=67 Participants Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle, 600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed.	Sorafenib (Nexavar, BAY43-9006)_600 mg Participants received 600 mg orally twice daily (bid)	Sorafenib (Nexavar, BAY43-9006)_800 mg Participants received 800 mg orally twice daily (bid)
Progression-free Survival (PFS)	7.4 months Interval 6.0 to 11.7	—	—

SECONDARY outcome

Population: Intent-to treat (ITT).

Time to progression (TTP) was defined as the time from start of study medication to the first documented disease progression per RECIST (by independent radiological assessment) or clinical progression as per investigator assessment whichever occurred first. For patients who had not progressed at the time of analysis or died before progression, TTP was censored at their last date of evaluable scan.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=67 Participants Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle, 600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed.	Sorafenib (Nexavar, BAY43-9006)_600 mg Participants received 600 mg orally twice daily (bid)	Sorafenib (Nexavar, BAY43-9006)_800 mg Participants received 800 mg orally twice daily (bid)
Time to Progression (TTP)	7.4 months Interval 6.0 to 11.7	—	—

OTHER_PRE_SPECIFIED outcome

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=18 Participants Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle, 600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed.	Sorafenib (Nexavar, BAY43-9006)_600 mg Participants received 600 mg orally twice daily (bid)	Sorafenib (Nexavar, BAY43-9006)_800 mg Participants received 800 mg orally twice daily (bid)
Tumor Response - mITT Population Complete response (CR)	0 Participants	—	—
Tumor Response - mITT Population Partial response (PR)	8 Participants	—	—
Tumor Response - mITT Population Stable disease (SD)	10 Participants	—	—
Tumor Response - mITT Population Progressive disease (PD)	0 Participants	—	—

OTHER_PRE_SPECIFIED outcome

Disease Control (DC) of a subject was defined as the proportion of patients with confirmed Complete Response (CR), Partial Response (PR) or Stable Disease (SD) as their best response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed CR was defined as disappearance of tumor, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, and SD was defined as steady state of disease.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=18 Participants Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle, 600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed.	Sorafenib (Nexavar, BAY43-9006)_600 mg Participants received 600 mg orally twice daily (bid)	Sorafenib (Nexavar, BAY43-9006)_800 mg Participants received 800 mg orally twice daily (bid)
Disease Control - mITT Population	18 Participants Interval 81.5 to 100.0	—	—

Adverse Events

Sorafenib (Nexavar, BAY43-9006)

Serious events: 45 serious events

Other events: 80 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sorafenib (Nexavar, BAY43-9006) n=83 participants at risk Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle,600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed.
Blood and lymphatic system disorders Hemoglobin	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Cardiac disorders Cardiac arrhythmia - Other	2.4% 2/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Cardiac disorders Cardiac general - Other	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Cardiac disorders Hypotension	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Cardiac disorders Left ventricular systolic dysfunction	2.4% 2/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Gastrointestinal disorders Colitis	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Gastrointestinal disorders Diarrhea	2.4% 2/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Gastrointestinal disorders GI - Other	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Constitutional symptoms - Other	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Fatigue	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Fever	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Abdomen NOS	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Back	2.4% 2/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Bone	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Breast	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Chest/Thorax NOS	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Joint	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Other	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Stomach	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Hepatobiliary disorders Cholecystitis	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Hepatobiliary disorders Hepatobiliary - Other	2.4% 2/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Immune system disorders Allergic reaction	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Infections and infestations Infection (Documented clinically), Kidney	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Infections and infestations Infection (Documented clinically), Lung (Pneumonia)	2.4% 2/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Infections and infestations Infection with normal ANC, Abdomen NOS	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Infections and infestations Infection with normal ANC, Anal/perianal	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Infections and infestations Infection with normal ANC, Sinus	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Injury, poisoning and procedural complications Intraop injury - Other	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders Hypercalcemia	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders Hyperglycemia	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders Hyperkalemia	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders Hypocalcemia	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders Hypomagnesemia	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders Hyponatremia	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders Hypophosphatemia	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Musculoskeletal and connective tissue disorders Fracture	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Musculoskeletal and connective tissue disorders Musculoskeletal - Other	2.4% 2/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Secondary malignancy (possibly related to cancer treatment)	2.4% 2/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Nervous system disorders Confusion	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Nervous system disorders Dizziness	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Nervous system disorders Neurology - Other	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Nervous system disorders Neuropathy: motor	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Nervous system disorders Neuropathy: sensory	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Renal and urinary disorders Renal failure	2.4% 2/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Respiratory, thoracic and mediastinal disorders Airway obstruction, Bronchus	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.4% 2/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Skin and subcutaneous tissue disorders Dermatology - Other	2.4% 2/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Skin and subcutaneous tissue disorders Erythema multiforme	1.2% 1/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Skin and subcutaneous tissue disorders Hand-foot skin reaction	2.4% 2/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Skin and subcutaneous tissue disorders Rash/desquamation	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Vascular disorders Thrombosis/Thrombus/Embolism	2.4% 2/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)

Other adverse events

Other adverse events
Measure	Sorafenib (Nexavar, BAY43-9006) n=83 participants at risk Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle,600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed.
Blood and lymphatic system disorders Edema: Limb	8.4% 7/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Blood and lymphatic system disorders Hemoglobin	14.5% 12/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Blood and lymphatic system disorders Neutrophils	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Blood and lymphatic system disorders Platelets	8.4% 7/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Cardiac disorders Hypertension	48.2% 40/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Cardiac disorders Hypotension	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Endocrine disorders Hyperthyroidism	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Endocrine disorders Hypothyroidism	14.5% 12/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Eye disorders Dry eye	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Eye disorders Ocular - Other	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Gastrointestinal disorders Anorexia	25.3% 21/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Gastrointestinal disorders Colitis	4.8% 4/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Gastrointestinal disorders Constipation	10.8% 9/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Gastrointestinal disorders Diarrhea	63.9% 53/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Gastrointestinal disorders Dry mouth	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Gastrointestinal disorders GI - Other	15.7% 13/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Gastrointestinal disorders Gastritis	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Gastrointestinal disorders Heartburn	9.6% 8/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Gastrointestinal disorders Hemorrhoids	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Gastrointestinal disorders Mucositis (clinical exam), Oral cavity	7.2% 6/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Gastrointestinal disorders Mucositis (functional/symptomatic), Oral cavity	33.7% 28/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Gastrointestinal disorders Nausea	26.5% 22/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Gastrointestinal disorders Taste Alteration	13.3% 11/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Gastrointestinal disorders Vomiting	19.3% 16/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Constitutional symptoms - Other	18.1% 15/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Fatigue	54.2% 45/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Fever	16.9% 14/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Flu-like syndrome	7.2% 6/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Insomnia	4.8% 4/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Abdomen NOS	12.0% 10/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Back	9.6% 8/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Bone	4.8% 4/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Breast	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Chest wall	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Chest/Thorax NOS	6.0% 5/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Dental/Teeth/peridontal	4.8% 4/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Extremity - limb	9.6% 8/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Head/Headache	8.4% 7/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Joint	7.2% 6/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Muscle	6.0% 5/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Other	7.2% 6/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Pain, Stomach	6.0% 5/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
General disorders Weight loss	16.9% 14/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Immune system disorders Allergy - Other	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Infections and infestations Infection (Documented clinically), Bladder (urinary)	7.2% 6/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Infections and infestations Infection (Documented clinically), Skin (Cellulitis)	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Infections and infestations Infection (Documented clinically), Urinary tract NOS	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Infections and infestations Infection - Other	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders ALT	8.4% 7/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders AST	7.2% 6/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders Amylase	6.0% 5/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders Creatinine	4.8% 4/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders GGT	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders Hyperkalemia	6.0% 5/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders Hyperuricemia	4.8% 4/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders Hypoalbuminemia	7.2% 6/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders Hypocalcemia	8.4% 7/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders Hypokalemia	9.6% 8/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders Hyponatremia	4.8% 4/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders Hypophosphatemia	19.3% 16/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders Lipase	19.3% 16/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Metabolism and nutrition disorders Metabolic/Lab - Other	8.4% 7/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Musculoskeletal and connective tissue disorders Musculoskeletal - Other	12.0% 10/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Nervous system disorders Dizziness	4.8% 4/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Nervous system disorders Mood Alteration, Anxiety	4.8% 4/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Nervous system disorders Mood alteration, Depression	7.2% 6/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Nervous system disorders Neurology - Other	4.8% 4/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Nervous system disorders Neuropathy: sensory	14.5% 12/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Renal and urinary disorders Cystitis	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Renal and urinary disorders Renal - Other	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Respiratory, thoracic and mediastinal disorders Cough	9.6% 8/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Respiratory, thoracic and mediastinal disorders Dyspnea (Shortness of breath)	18.1% 15/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Respiratory, thoracic and mediastinal disorders Pulmonary - Other	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Respiratory, thoracic and mediastinal disorders Voice changes	13.3% 11/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Skin and subcutaneous tissue disorders Alopecia	43.4% 36/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Skin and subcutaneous tissue disorders Dermatology - Other	22.9% 19/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Skin and subcutaneous tissue disorders Dry skin	27.7% 23/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Skin and subcutaneous tissue disorders Erythema multiforme	7.2% 6/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Skin and subcutaneous tissue disorders Flushing	6.0% 5/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Skin and subcutaneous tissue disorders Hand-foot skin reaction	65.1% 54/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Skin and subcutaneous tissue disorders Nail changes	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Skin and subcutaneous tissue disorders Pruritus	18.1% 15/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Skin and subcutaneous tissue disorders Rash/desquamation	55.4% 46/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Vascular disorders Hemorrhage pulmonary, Nose	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Vascular disorders Hemorrhage, GI, Oral cavity	4.8% 4/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Vascular disorders Thrombosis/Thrombus/Embolism	3.6% 3/83 Abbreviations used in the Adverse Events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)

Additional Information

Therapeutic Area Head

BAYER

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Principal Investigator (PI) can publish results following completion of study. The PI must discuss a publication with Bayer prior to release\&obtain written consent to proceed. The Investigator must send a draft to Bayer at least 30d in advance of submission to obtain approval. Any submission to Bayer will be reviewed w/o unreasonable delay\&approval not be withheld unreasonably. In difference of opinion publication will be discussed.
Publication restrictions are in place

Restriction type: OTHER