12

mg/m^2

Intravenous (IV)

once a day

on 2, 4, 6, and 8 days in combination with tretinoin

Acute Promyelocytic Leukemia
Induction of remission-
45 mg/m² orally each day divided every 12 hours
30 days later the completion of remission or 90 days post-initiation of treatment

Induction of remission combined with anthracycline
45 mg/m² orally each day divided every 12 hours

Off-Label Consolidation
45 mg/m² orally each day divided every 12 hours for 15 days in a month for 3 months

Off-Label Remission Maintenance
45 mg/m² orally each day divided every 12 hours for 15 days every quarter year for 2 years

Dose Adjustment
In the case of toxicity (APL differentiation syndrome)
10 mg dexamethasone intravenously every 12 hours for 3-5 days

Newly diagnosed low-risk acute promyelocytic leukemia (APL)
Treatment therapy involves of 1 induction and 4 consolidation cycles
Induction cycle
Administer arsenic trioxide at a dose of 0.15 mg/kg intravenously daily until achieving bone marrow remission, with a maximum duration of 60 days, in addition to
Take tretinoin at a dose of 22.5 mg/m² orally twice a day until achieving bone marrow remission, with a maximum duration of 60 days
Consolidation cycle
Administer arsenic trioxide at a dose of 0.15 mg/kg intravenously daily for first 5 days on weeks 1 to 4 of an 8-week cycle and that to total of 4 cycles when combined with tretinoin
Take tretinoin 22.5 mg/m² orally twice daily for first 7 days on weeks 1, 2, 5, and 6
Tretinoin should be omitted during weeks 5 and 6 of the fourth cycle of consolidation
Dosage Modifications
Differentiation syndrome
If symptoms are severe, consider discontinuing tretinoin
Administer dexamethasone 10 mg intravenously every 12 hours until the indications and symptoms go away, for at least 3 days
QTc prolongation
If half amount of dose is well-tolerated for a week, then raise the dose up to 0.11 mg/kg every day for a week
Hepatoxicity
If hepatotoxicity returns, permanently stop taking the drugs that were withheld
Myelosuppression
Consider decreasing dose of arsenic trioxide and tretinoin by 1 dose level
Dosing reduction levels for hematologic and nonhematologic toxicities
For arsenic trioxide
Starting level: 0.15 mg/kg intravenously daily
Level- 1: 0.11 mg/kg intravenously daily
Level- 2: 0.1 mg/kg intravenously daily
Level- 3: 0.075 mg/kg intravenously daily
For tretinoin
Starting level: 22.5 mg/m² orally twice a day
Level- 1: 18.75 mg/m² orally twice a day
Level- 2: 12.5 mg/m² orally twice a day
Level- 3: 10 mg/m² orally twice a day
Renal impairment
Severe: There may be increased exposure to arsenic trioxide
Safety and efficacy not determined for dialysis
Hepatic impairment
Limited data present
Severe (Child Pugh C): Monitor for poisoning

5

mg/m^2

Intravenous (IV)

once a day

for 4 days in combination with cytarabine, etoposide, thioguanine, and dexamethasone

Induction of remission-
25 mg/m² orally each day divided every 12 hours
30 days later the completion of remission or 90 days post-initiation of treatment

Induction of remission combined with anthracycline
25 mg/m² orally each day divided every 12 hours

Off-Label Consolidation
25 mg/m² orally each day divided every 12 hours for 15 days in a month for 3 months

Off-Label Remission Maintenance
25 mg/m² orally each day divided every 12 hours for 15 days every quarter year for 2 years

Dose Adjustment
In the case of toxicity (APL differentiation syndrome)
10 mg dexamethasone intravenously every 12 hours for 3-5 days

Refractory after retinoid and anthracycline chemotherapy
<4 years: Safety and efficacy not determined
≥4 years: Administer dose of 0.15 mg/kg intravenously daily until achieving bone marrow remission, with a maximum duration of 60 days
Wait for 3 to 6 weeks, then
Administer dose of 0.15 mg/kg intravenously daily for 25 doses
Dosing Considerations
Monitor: serum electrolytes and ECG