CTCAE v 4.01
ONIVYDE/5-FU adjustment
(for patients not homozygous for UGT1A1*28)
Haematological toxicities
Neutropenia
A new cycle of therapy should not begin until the absolute neutrophil count is ≥ 1500/mm3
Grade 3 or Grade 4 (< 1000/mm3) or Neutropenic fever
First occurrence
Reduce ONIVYDE dose to 60 mg/m2
Reduce 5-FU dose by 25% (1800 mg/m2)
Second occurrence
Reduce ONIVYDE dose to 50 mg/m2
Reduce 5-FU dose by an additional 25% (1350 mg/m2)
Third occurrence
Discontinue treatment
Thrombocytopenia
Leukopenia
A new cycle of therapy should not begin until the platelet count is ≥ 100,000/mm3
Dose modifications for leukopenia and thrombocytopenia are based on NCI CTCAE toxicity grading and are the same as recommended for neutropenia above.
Nonhaematological toxicities2
Diarrhoea
A new cycle of therapy should not begin until diarrhoea resolves to ≤ Grade 1 (2-3 stools/day more than pre-treatment frequency).
Grade 2
A new cycle of therapy should not begin until diarrhoea resolves to ≤ Grade 1 (2-3 stools/day more than pre-treatment frequency).
Grade 3 or 4
First occurrence
Reduce ONIVYDE dose to 60 mg/m2
Reduce 5-FU dose by 25% (1800 mg/m2)
Second occurrence
Reduce ONIVYDE dose to 50 mg/m2
Reduce 5-FU dose by an additional 25% (1350 mg/m2)
Third occurrence
Discontinue treatment
Nausea/vomiting
A new cycle of therapy should not begin until nausea/vomiting resolves to ≤ Grade 1 or baseline
Grade 3 or 4 (despite antiemetic therapy)
First occurrence
Optimise antiemetic therapy
Reduce ONIVYDE dose to 60 mg/m2
Second occurrence
Optimise antiemetic therapy
Reduce ONIVYDE dose to 50 mg/m2
Third occurrence
Discontinue treatment
Hepatic, renal, respiratory or other2 toxicities
Grade 3 or 4
A new cycle of therapy should not begin until the adverse reaction resolves to ≤ Grade 1
First occurrence
Reduce ONIVYDE dose to 60 mg/m2
Reduce 5-FU dose by 25% (1800 mg/m2)
Second occurrence
Reduce ONIVYDE dose to 50 mg/m2
Reduce 5-FU dose by an additional 25% (1350 mg/m2)
Third occurrence
Discontinue treatment
Anaphylactic reaction
First occurrence
Discontinue treatment
1 NCI CTCAE v 4.0 = National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
2 Excludes asthenia and anorexia; Asthenia and Grade 3 anorexia do not require dose adjustment.
Table 2: Recommended dose modifications for ONIVYDE +5-FU/LV for Grade 3-4 toxicities in patients homozygous for UGT1A1*28
Toxicity grade (value) by NCI CTCAE v 4.01
ONIVYDE/5-FU adjustment
(for patients homozygous for UGT1A1*28 without previous increase to 80 mg/m2)
Adverse reactions2 Grade 3 or 4
A new cycle of therapy should not begin until adverse event resolves to ≤ Grade 1
First occurrence
Reduce ONIVYDE dose to 50 mg/m2
5-FU dose modification as in Table 1
Second occurrence
Reduce ONIVYDE dose to 40 mg/m2
5-FU dose modification as in Table 1
Third occurrence
Discontinue treatment
1 NCI CTCAE v 4.0 = National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
2 Excludes asthenia and anorexia; asthenia and Grade 3 anorexia do not require dose adjustment.
Special populations
Hepatic impairment
No dedicated hepatic impairment study has been conducted with ONIVYDE. The use of ONIVYDE should be avoided in patients with bilirubin > 2.0 mg/dl, or aspartate aminotransferase (AST) and alanine aminotransferase (AL |
