Table 1 Dose limiting toxicity and maximum grade of all hepatic toxicities for all 15 patients enrolled on NANT 2004–04
Total dose of IV fenretinide | # patients enrolled (# evaluable for dose escalation) | Patient Age at study entry (years) | Fenretinide peak level Course 1 (μM) | Dose Limiting Toxicity | Total number courses/Hepatic toxicities (maximum grade (Gr) across all courses received ) | Ceftriaxone during or after fenretinide | Acetaminophen during or after fenretinide |
|---|---|---|---|---|---|---|---|
Level 1: 640 mg/m2/day | 3 (3) | 7.9 | 30.5 | None | 6 courses: Gr 2 AST, Gr 2 hypoalbuminemia, Gr 1 hyperbilirubinemia | 3 days during Course 6 | |
8.5 | 17.2 | None | 1 course: Gr 1 hypoalbuminemia, Gr 1 AST | 1 dose 2 days after Course 1 | |||
24 | 30.1 | None | 2 courses; none | ||||
Level 2: 770 mg/m2/day | 3 (3) | 4.2 | 40.7 | None | 30 courses: Gr. 3 ALT, Gr 3 AST, Gr. 2 hypoalbuminemia, Gr 1 alkaline phosphatase. Got dose level 1 for courses 26–30 due to delayed platelet recovery course 25. | 20 doses starting after completion of Course 14 | |
4.4 | 70.2 | None | 4 courses; Grade 1 AST | ||||
5 | 39.4 | Gr 3 hypoalbuminemia* | 1 course: Gr 3 AST, Gr 3 hypoalbuminemia* | ||||
Level 3: 925 mg/m2/day | 7 ( 6 ) | 6.7 | 36.3 | None | 2 courses: Gr. 1 ALT, Gr 1 AST, Gr. 1 hypoalbuminemia | 4 doses during Course 3 | |
5.2 | 38.4 | None | 6 courses; Gr 1 AST, Gr 1 hypoalbuminemia, Gr 2 hyperbilirubinemia | 2 days during Course 1 | |||
9.7 | 60.7 | Gr 4 hypertriglyceridemia due to error in drug infusion | 1 course: Not evaluable for dose escalation due to error in drug infusion with 24 hour dose given over 12 hours; Gr 1 hypoalbuminemia, Gr 2 hyperbilirubinemia | ||||
11.4 | 33.0 | Pseudotumor cerebri | 1 course: Gr 3 ALT, Gr 2 AST | ||||
11 | 29.1 | None | 1 course; Gr 1 ALT, Gr 2 AST, Gr 1 hypoalbuminemia | ||||
5.3 | 23.7 | None | 2 courses: Gr 1 AST | ||||
12.6 | 45.0 | None | 2 courses; Gr 1 ALT, Gr 2 AST | ||||
Level 4: 1110 mg/m2/day | 2 (2) | 5.5 | 83.3 | Gr 4 epistaxis related to multi organism non-neutropenic bacteremia during course 5 | 5 courses: Gr 1 ALT, Gr 2 AST, Gr 2 hypoalbuminemia, Gr 1 alkaline phosphatase | 4 days starting 9 days after completion of Course 5 | |
7.2 | 110.9 | Fatal hepatic failure, renal failure, and hypotension** | 1 course (subject of this case report): Gr 5 liver dysfunction/failure (clinical), Gr 4 ALT, Gr 4 AST, Gr 4 hyperbilirubinemia; Gr 3 hypoalbuminemia; Gr 1 alkaline phosphatase | 3 days starting 4th day of the infusion | 9 doses starting 4th day of the infusion | ||
Level 3a: 925 mg/m2/day | 2 (0) | 6.7 | 14.17# | None | 2 courses: Gr 1 ALT/Gr 1 AST | ||
7.8 | 21.93# | None | 5 courses:Gr 1 AST, Gr 1 hypalbuminemia, Gr 1 alkaline phosphatase |