Background
Methods
Eligibility criteria
Study design
Treatment
Assessment
Pharmacokinetic assessments
Statistical analysis
Results
Patient characteristics
Characteristic | Number of patients | |||||
---|---|---|---|---|---|---|
Four consecutive weeks | 2-week on/1-week off | |||||
5 mg/person | 10 mg/person | 10 mg/person | 12 mg/person | 16 mg/person | ||
Total | 4 | 4 | 3 | 21 | 3 | |
Sex | Male | 2 | 2 | 2 | 15 | 1 |
Female | 2 | 2 | 1 | 6 | 2 | |
Age, year | Median | 39 | 50 | 60 | 47 | 45 |
Range | 21–49 | 39–60 | 53–65 | 32–60 | 48–55 | |
ECOG score | 0 | 0 | 1 | 0 | 9 | 0 |
1 | 4 | 3 | 3 | 12 | 3 | |
Pretreatment | Surgery | 3 | 4 | 2 | 18 | 2 |
Radiotherapy | 2 | 1 | 3 | 6 | 1 | |
Chemotherapy | 4 | 4 | 3 | 15 | 3 | |
Tumor site | Sarcoma | 2 | 1 | 1 | 4 | 1 |
MTC | 0 | 0 | 0 | 6 | 0 | |
CC | 1 | 2 | 0 | 0 | 1 | |
NSCLC | 0 | 0 | 1 | 3 | 0 | |
RC | 0 | 0 | 0 | 4 | 0 | |
Other | 1 | 1 | 1 | 4 | 1 |
Safety and tolerability
Adverse events | Grade 1/2 | Grade 3 | ||||||
---|---|---|---|---|---|---|---|---|
First 2 cycles | All cycles | First 2 cycles | All cycles | |||||
No. of patients | % | No. of patients | % | No. of patients | % | No. of patients | % | |
Occurred at least one time | 21 | 100 | 21 | 100 | 2 | 10 | 6 | 29 |
Hand-foot skin reaction | 4 | 19 | 10 | 48 | 0 | 0 | 1 | 5 |
Rash | 4 | 19 | 6 | 29 | 0 | 0 | 0 | 0 |
Hypertension | 5 | 24 | 5 | 24 | 0 | 0 | 2 | 10 |
Proteinuria | 5 | 24 | 14 | 67 | 0 | 0 | 0 | 0 |
Triglyceride elevation | 6 | 29 | 11 | 52 | 1 | 5 | 2 | 10 |
Total cholesterol elevation | 6 | 29 | 13 | 62 | 0 | 0 | 0 | 0 |
Hypothyroidism | 8 | 38 | 12 | 57 | 0 | 0 | 0 | 0 |
Hyperthyroidism | 2 | 10 | 2 | 10 | 0 | 0 | 0 | 0 |
ALT elevation | 6 | 29 | 10 | 48 | 0 | 0 | 0 | 0 |
AST elevation | 4 | 19 | 9 | 43 | 0 | 0 | 0 | 0 |
Creatinine elevation | 1 | 5 | 2 | 10 | 0 | 0 | 0 | 0 |
Total bilirubin elevation | 5 | 24 | 8 | 38 | 0 | 0 | 0 | 0 |
Lipase elevation | 1 | 5 | 5 | 24 | 1 | 5 | 1 | 5 |
Serum amylase | 4 | 19 | 9 | 43 | 0 | 0 | 0 | 0 |
Myocardial enzymes abnormal | 2 | 10 | 3 | 14 | 0 | 0 | 0 | 0 |
Leukopenia | 3 | 14 | 6 | 29 | 0 | 0 | 0 | 0 |
Neutropenia | 0 | 0 | 2 | 10 | 0 | 0 | 0 | 0 |
Thrombocytopenia | 0 | 0 | 2 | 10 | 0 | 0 | 0 | 0 |
Hemorrhage | 0 | 0 | 1 | 5 | 0 | 0 | 0 | 0 |
Urine occult blood | 5 | 24 | 8 | 38 | 0 | 0 | 0 | 0 |
Fatigue | 5 | 24 | 7 | 33 | 0 | 0 | 0 | 0 |
Diarrhea | 6 | 29 | 7 | 33 | 0 | 0 | 0 | 0 |
Hoarseness | 3 | 14 | 5 | 24 | 0 | 0 | 0 | 0 |
Nausea | 3 | 14 | 3 | 14 | 0 | 0 | 0 | 0 |
Inappetence | 1 | 5 | 2 | 10 | 0 | 0 | 0 | 0 |
Toothache | 1 | 5 | 4 | 19 | 0 | 0 | 0 | 0 |
Pharyngalgia | 1 | 5 | 4 | 19 | 0 | 0 | 0 | 0 |
Premature beat | 0 | 0 | 1 | 5 | 0 | 0 | 0 | 0 |
Efficacy
Pharmacokinetics
Pharmacokinetic parameters | Measurement of dose-dependent pharmacokinetics | Assessment of dose proportionality | ||||||
---|---|---|---|---|---|---|---|---|
5 mg/person (n = 1) | 10 mg/person (n = 4) | 12 mg/person (n = 11) | 16 mg/person (n = 4) |
r
|
P
| Slope (90 % CI) | Conclusion | |
C
max, ng/mL | 5.8 | 5.8 ± 2.8 | 10.5 ± 2.9 | 15.8 ± 3.2 | 0.629 | 0.003 | 1.12 (0.54–1.71) | Inconclusive |
T
max, h | 11.0 | 6.0 ± 4.4 | 7.3 ± 3.3 | 11.0 ± 8.9 | – | – | – | – |
AUC0–120h, h·ng/mL | 411 | 318 ± 133 | 617 ± 194 | 894 ± 305 | 0.465 | 0.045 | 0.81 (0.16–1.45) | Inconclusive |
AUC0–∞, h·ng/mL | 687 | 562 ± 328 | 1066 ± 263 | 1585 ± 470 | 0.666 | 0.002 | 1.18 (0.62–1.73) | Inconclusive |
t
1/2, h | 102 | 95 ± 22 | 116 ± 47 | 98 ± 15 | – | – | – | – |