Table 4.
Summary of Adverse Events for All Treatment Cycles
| 100 mg qd1 N=6 |
120 mg qd N=3 |
150 mg qd2 N=11 |
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| Grade | 1 | 2 | 3 | 4 | 1 | 2 | 3 | 4 | 1 | 2 | 3 | 4 |
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| Variable | ||||||||||||
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| Hematologic | ||||||||||||
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| Anemia | 1 (17) | 4 (67) | 1 (17) | - | - | 2 (67) | 1 (33) | - | 2 (18) | 4 (36) | 3 (27) | 1 (9) |
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| Neutropenia | - | - | 2 (33) | 4 (67) | - | - | 1 (33) | 2 (67) | - | - | 1 (9) | 9 (82) |
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| Febrile Neutropenia | - | - | - | 1 (17)3 | - | - | - | - | - | - | 1 (9) | - |
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| Thrombocytopenia | 2 (33) | 1 (17) | 1 (17) | 1 (17) | - | - | 1 (33) | - | 1 (9) | 4 (36) | 2 (18) | 2 (18) |
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| Allergy | - | - | 1 (17) | - | - | - | 1 (33) | - | 1 (9) | 1 (9) | - | - |
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| Fatigue | 2 (33) | 1 (17) | 2 (33) | - | 3 (100) | - | - | - | 3 (27) | 7 (64) | - | - |
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| Dermatogic | ||||||||||||
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| Flushing | 1 (17) | - | - | - | 1 (33) | - | - | - | 1 (9) | - | 1 (9) | - |
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| Alopecia | - | 6 (100) | - | - | 1 (33) | 2 (67) | - | - | 2 (18) | 8 (73) | - | - |
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| Pruritis | - | 1 (17) | - | - | - | - | - | - | 1 (9) | - | - | - |
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| Rash | - | - | - | - | - | - | - | - | 3 (27) | - | - | - |
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| Gastrointestinal4, 5 | ||||||||||||
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| Anorexia | 2 (33) | 1 (17) | - | - | 3 (100) | - | - | - | 5 (45) | 3 (27) | - | - |
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| Constipation | - | 2 (33) | - | - | 1 (33) | - | - | - | 4 (36) | 1 (9) | - | - |
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| Diarrhea | 4 (67) | 2 (33) | - | - | 3 (100) | - | - | - | 6 (55) | 1 (9) | - | - |
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| Mucositis/Stomatitis | 2 (33) | - | - | - | 1 (33) | - | - | - | - | - | - | - |
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| Nausea | 2 (33) | 2 (33) | - | - | 3 (100) | - | - | - | 4 (36) | 5 (45) | - | - |
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| Dysgeusia | 1 (17) | - | - | - | - | - | - | - | 1 (9) | - | - | - |
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| Vomiting | 2 (33) | 1 (17) | - | - | 2 (67) | - | - | - | 4 (36) | 3 (27) | - | - |
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| Metabolic6,7 | ||||||||||||
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| Electrolyte | 1 (17)6 | - | - | - | 2 (67)6 | - | - | - | 7 (64)6 | 5 (45)6 | 2 (18)6 | 1 (9)6 |
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| Hyperglycemia | - | - | - | - | - | - | - | - | 1 (9) | 2 (18) | - | - |
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| Neurologic8 | ||||||||||||
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| Anxiety | - | 1 (17) | - | - | - | - | - | - | - | 1 (9) | - | - |
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| Sensory neuropathy | 3 (50) | 1 (17) | - | - | 2 (67) | - | - | - | 5 (45) | 1 (9) | 1 (9) | - |
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| Ocular | 1 (17) | - | - | - | 1 (33) | - | - | - | - | - | - | - |
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| Pain9 | ||||||||||||
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| Head | 1 (17) | - | - | - | - | - | - | - | 3 (27) | - | - | - |
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| Joint | - | 2 (33) | - | - | - | 1 (33) | - | - | - | - | 1 (9) | - |
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| Muscle | - | 1 (17) | 1 (17)1 | - | - | - | - | - | - | - | - | - |
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| Other | 1 (17) | - | 1 (17) | - | - | - | - | - | 1 (9) | - | 1 (9) | - |
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| Pulmonary10 | ||||||||||||
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| Cough | 1 (17) | - | - | - | 1 (33) | - | - | - | 2 (18) | - | - | - |
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| Dyspnea | - | - | 1 (17) | - | 2 (67) | 1 (33) | - | - | 3 (27) | 1 (9) | 1 (9) | - |
Additional toxicities in cohort 1 included musculoskeletal toxicity characterized by grade 1 joint-function toxicity (n=1) and grade 1 muscular complaints (n=1). The grade 3 myalgia is reported under pain.
Additional toxicities in cohort 3 included the following: grade 3 hypotension (n=1), grade 1 weight loss (n=2), grade 1 epitaxis (n=1), and grade 1 facial and neck edema (n=1).
There was one report of infection associated with febrile neutropenia. Two other infections occurred including 1 urinary tract infection occurred in cohort 1.
Gastrointestinal toxicity also included the following: (1) grade 1 dehydration (n=1) in cohort 1; (2) grade 1 distension (n=1), grade 1 xerostomia (n=1), grade 1 gastritis (n=1) in cohort 2; and (3) grade 1 xerostomia (n=1) in cohort 3.
Gastrointestinal toxicity included other unspecified etiologies: (1) grade 1 (n=1) and grade 2 (n=1) in cohort 1; (2) grade 1 (n=1) in cohort 2; and (3) grade 1 (n=1) in cohort 3.
Electrolyte abnormalities were the following: (1) grade 1 hyponatremia (n=1) in cohort 1; (2) grade 1 hypomagnesemia (n=1) and hypokalemia (n=1) in cohort 2; and (3) grade 3 hypercalcemia (n=1); grade 2 hypocalcemia (n=1); hypomagnesemia (grade 1 (n=2), grade 2 (n=1)); hypophosphatemia (grade 2 (n=2), grade 3 (n=1)); hypokalemia (grade 1 (n=3), grade 4 (n=1)); and grade 1 hyponatremia (n=2) in cohort 3. More than one electrolyte abnormality may have occurred in one patient.
Metabolic toxicities also included the following: grade 1 elevated transaminases (n=1), grade 1 elevated alkaline phosphatase (n=1), and proteinuria (grade 1 (n=1), grade 2 (n=1)) in cohort 3.
Neurologic toxicity included one case of grade 1 somnolence/depressed level of consciousness in cohort 2.
Pain toxicity also included the following: (1) grade 2 neuralgia (n=1), grade 1 sinus pain (n=1), and grade 1 throat pain (n=1) in cohort 1; and (2) grade 1 back pain (n=1) and grade 1 extremity pain (n=1) in cohort 2.
Pulmonary toxicity also included the following: (1) grade 1 other unspecified etiology (n=1) in cohort 1; and (2) grade 2 hypoxia (n=1 in cohort 2.