Table 1

Dose modifications for ISIS 3521 and 5-FU based on toxicity

ToxicityCTC gradeDose modification
Neutropenia1None
2None
3None
4Hold therapy until <grade 2, reduce dose of ISIS 3521 and 5-FU according to protocola
Neutropenic feverHold therapy until fever has resolved and neutropenia ≤grade 2, reduce dose of ISIS 3521 and 5-FU according to protocola
Thrombocytopenia1None
2None
3If with bleeding, hold therapy until ≤grade 1 and then reduce dose of ISIS 3521 and 5-FU according to protocol;a if without bleeding, no dose modifications required
4Hold therapy until ≤grade 1 and then reduce dose of ISIS 3521 and 5-FU according to protocola
Diarrhea1–2None
3–4Hold 5-FU until ≤grade 2 and then reduce dose of 5-FU according to protocola
Nausea/vomiting1–3None
4If on maximal antiemetic therapy, hold 5-FU dose until ≤grade 2 and then reduce dose of 5-FU according to protocola
Coagulation (PT/aPTT)1–3None
4If associated with ≥grade 2 bleeding, reduce dose of ISIS 3521 according to protocola
Other toxicities
(Except alopecia)1None
2None
3–4Hold therapy until ≤grade 2 and then decrease dose of ISIS 3521 and 5-FU according to protocola
  • a Decrease ISIS 3521 by 1.0 mg/kg/day to a minimum of 1.0 mg/kg/day. Decrease 5-FU from 425 mg/m2 to 375 mg/m2, from 375 mg/m2 to 325 mg/m2, and decrease thereafter in 25% decrements to a minimum of 200 mg/m2