Table 1 Summary of adverse events and treatment-emergent toxicities by cohort.
Cohort (Single dose) | 1 (1866 mg/m2) n = 4 | 2 (3732 mg/m2) n = 3 | 3 (5600 mg/m2) n = 3 | 4 (7000 mg/m2) n = 4 | 5 (8750 mg/m2) n = 3 | 6 (10,500 mg/m2) n = 4 | 7 (12,390 mg/m2) n = 3 | 8 (14,500 mg/m2) n = 4 | All n = 28 |
|---|---|---|---|---|---|---|---|---|---|
Treatment-emergent toxicities (TET) judged to be definitively, probably or possibly related to ITPP | |||||||||
Hypercalcemia | 0 | 1x Grade I | 1x Grade I | 4x Grade I | 2x Grade I | 4x Grade I | 3x Grade I | 2x Grade I 1x Grade II (sTET) 1x Grade IV (DLT) | 17x Grade I 1x Grade II 1x Grade IV Total: 19 (67.9%) |
Hypomagnesemia | 0 | 1x Grade I | 0 | 0 | 0 | 1x Grade I | 0 | 3x Grade I | Total: 5 (17.9%) |
Hypophosphatemia | 0 | 0 | 1x Grade I | 3x Grade I | 0 | 0 | 0 | 0 | Total: 4 (14.3%) |
Hyperphosphatemia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1x Grade I | Total: 1 (3.6%) |
Hypertension | 0 | 0 | 0 | 1x Grade I | 0 | 0 | 0 | 2x Grade I | Total: 3(10.7%) |
Other adverse events (AE) & serious adverse events (SAE) judged to be unlikely or definitively unrelated to ITPP | |||||||||
Acute kidney injury grade 3 | 0 | 0 | 0 | 1x Grade III (SAE) | 0 | 0 | 0 | 0 | Total: 1 (3.6%) |
Ascites due to oncological progress | 1x Grade V (SAE) | 0 | 0 | 1x Grade I | 0 | 0 | 1x Grade III | 0 | Total: 3 (10.7%) |
AV Block 1° | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1x Grade I | Total: 1 (3.6%) |
C. difficile enteritis | 0 | 0 | 1x Grade III (SAE) | 0 | 0 | 0 | 0 | 0 | Total: 1 (3.6%) |
Cholestasis | 0 | 0 | 1x Grade III (SAE) | 0 | 0 | 0 | 0 | 0 | Total: 1 (3.6%) |
Fatigue | 0 | 0 | 0 | 1x Grade III (SAE) | 0 | 0 | 0 | 0 | Total: 1 (3.6%) |
Hypokalemia | 0 | 0 | 0 | 0 | 1x Grade II | 0 | 1x Grade I | 0 | Total: 2 (7.1%) |
Hyponatremia | 0 | 0 | 0 | 0 | 1x Grade I | 0 | 1x Grade I 1x Grade II | 0 | Total: 3 (10.7%) |
Icterus due to malignant obstruction | 0 | 0 | 0 | 0 | 1x Grade III | 0 | 0 | 0 | Total: 1 (3.6%) |
Lower gastrointestinal bleeding | 1x Grade II (SAE) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | Total: 1 (3.6%) |
Nausea | 0 | 0 | 0 | 1x Grade I | 0 | 0 | 0 | 0 | Total: 1 (3.6%) |
Nausea & vomiting due to malignant infiltration of stomach | 0 | 1x Grade II (SAE) | 0 | 0 | 0 | 0 | 0 | 0 | Total: 1 (3.6%) |
Neutropenia | 0 | 0 | 0 | 0 | 0 | 1x Grade III | 0 | 0 | Total: 1 (3.6%) |
Palpitations | 0 | 0 | 1x Grade I | 0 | 0 | 0 | 0 | 0 | Total: 1 (3.6%) |
Pyrexia | 1x Grade I | 0 | 0 | 0 | 0 | 0 | 1x Grade I | 0 | Total: 2 (7.1%) |
Upper respiratory tract infection | 0 | 0 | 0 | 2x Grade I | 0 | 0 | 1x Grade II | 0 | Total: 3 (10.7%) |
