Systemic Anti-Cancer Therapy Regimen Library
APML4 [60 years and under] - Induction (LEU APL - APML4 induction, consolidation 1 and 2 followed by maintenance [60 years and under])
Treatment Overview
Differentiation syndrome:
- Monitor closely for differentiation syndrome in the first 7 to 10 days of treatment.
- Prompt recognition and treatment with high dose intravenous corticosteroids is necessary until 3 days or longer after complete resolution of symptoms.
- Decision to withhold tretinoin and arsenic trioxide should be only for severe cases or if lack of response to corticosteroid.
Cycle 1 - 36 days
prEDNISone: Take until white cell count less than 1 x 109/L, or until resolution of differentiation syndrome.
tretinoin:
- Consider dose reduction of tretinoin to 25 mg/m2 daily in TWO divided doses in patients under 20 years of age to reduce risk of pseudotumour cerebri.
- Teratogenic—Ensure pregnant women are not exposed to tretinoin. Consult prescribing information.
arsenic trioxide:
- May prolong QTc interval and close monitoring is recommended. Avoid or reduce risk factors for QTc prolongation.
- Azole antifungals may increase QTc interval. Consult prescribing information.
Cycle details
Cycle 1 - 36 days
| Medication | Dose | Route | Days | Max Duration |
|---|---|---|---|---|
| prEDNISone | 1 mg/kg Once daily | oral administration | 1 to 10 | |
| tretinoin | 45 mg/m² Daily in divided doses | oral administration | 1 to 36 | |
| IDArubicin * | 12 mg/m² | intravenous | 2, 4, 6, 8 |
15 minutes |
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 9 to 36 | 120 minutes |
prEDNISone: Take until white cell count less than 1 x 109/L, or until resolution of differentiation syndrome.
tretinoin:
- Consider dose reduction of tretinoin to 25 mg/m2 daily in TWO divided doses in patients under 20 years of age to reduce risk of pseudotumour cerebri.
- Teratogenic—Ensure pregnant women are not exposed to tretinoin. Consult prescribing information.
arsenic trioxide:
- May prolong QTc interval and close monitoring is recommended. Avoid or reduce risk factors for QTc prolongation.
- Azole antifungals may increase QTc interval. Consult prescribing information.
Full details
Cycle 1 - 36 days
Day: 1
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| prEDNISone | 1 mg/kg Once daily | oral administration |
Instructions:
In the morning with food until WCC < 1 x 109/L or until resolution of differentiation syndrome. |
|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
Day: 2
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| prEDNISone | 1 mg/kg Once daily | oral administration |
Instructions:
In the morning with food until WCC < 1 x 109/L or until resolution of differentiation syndrome. |
|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| IDArubicin * | 12 mg/m² | intravenous | 15 minutes |
Instructions:
Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration. |
Day: 3
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| prEDNISone | 1 mg/kg Once daily | oral administration |
Instructions:
In the morning with food until WCC < 1 x 109/L or until resolution of differentiation syndrome. |
|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
Day: 4
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| prEDNISone | 1 mg/kg Once daily | oral administration |
Instructions:
In the morning with food until WCC < 1 x 109/L or until resolution of differentiation syndrome. |
|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| IDArubicin * | 12 mg/m² | intravenous | 15 minutes |
Instructions:
Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration. |
Day: 5
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| prEDNISone | 1 mg/kg Once daily | oral administration |
Instructions:
In the morning with food until WCC < 1 x 109/L or until resolution of differentiation syndrome. |
|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
Day: 6
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| prEDNISone | 1 mg/kg Once daily | oral administration |
Instructions:
In the morning with food until WCC < 1 x 109/L or until resolution of differentiation syndrome. |
|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| IDArubicin * | 12 mg/m² | intravenous | 15 minutes |
Instructions:
Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration. |
Day: 7
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| prEDNISone | 1 mg/kg Once daily | oral administration |
Instructions:
In the morning with food until WCC < 1 x 109/L or until resolution of differentiation syndrome. |
|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
Day: 8
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| prEDNISone | 1 mg/kg Once daily | oral administration |
Instructions:
In the morning with food until WCC < 1 x 109/L or until resolution of differentiation syndrome. |
|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| IDArubicin * | 12 mg/m² | intravenous | 15 minutes |
Instructions:
Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration. |
Day: 9
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| prEDNISone | 1 mg/kg Once daily | oral administration |
Instructions:
In the morning with food until WCC < 1 x 109/L or until resolution of differentiation syndrome. |
|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 10
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| prEDNISone | 1 mg/kg Once daily | oral administration |
Instructions:
In the morning with food until WCC < 1 x 109/L or until resolution of differentiation syndrome. |
|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 11
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 12
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 13
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 14
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 15
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 16
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 17
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 18
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 19
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 20
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 21
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 22
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 23
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 24
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 25
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 26
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 27
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 28
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 29
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 30
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 31
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 32
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 33
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 34
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 35
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Day: 36
| Medication | Dose | Route | Max duration | Details |
|---|---|---|---|---|
| tretinoin | 45 mg/m² Daily in divided doses | oral administration |
Instructions:
Additional details:
Daily in TWO divided doses.
|
|
| arsenic trioxide | 0.15 mg/kg Once daily | intravenous | 120 minutes |
Additional details
Section 1: Teratogenic effects
Ensure pregnant women are not exposed to tretinoin. Consult prescribing information.
Supportive Care Factors
| Factor | Value |
|---|---|
| Antifungal prophylaxis: | Routine antifungal prophylaxis recommended |
| Antiviral prophylaxis for herpes virus: | Routine antiviral prophylaxis recommended |
| Emetogenicity: | Variable |
| Gastroprotection: | Gastroprotection may be considered |
| Pneumocystis jirovecii pneumonia (PJP) prophylaxis: | Routine antibiotic prophylaxis may be considered |
| Tumour lysis syndrome prophylaxis: | Tumour lysis syndrome prophylaxis is recommended |
Antifungal prophylaxis: Azole antifungals may increase QTc interval. Consult prescribing information.
Antiviral prophylaxis for hepatitis B virus: Guidance is limited to high-risk anti-cancer medicines. Clinicians will need to assess individual patient risk for other anti-cancer medicines.
Emetogenicity:
- MEDIUM days 2, 4, 6, 8.
- MINIMAL to LOW (oral) days 1, 3, 5, 7.
- LOW days 9 to 36.
References
Phebra NZ Limited Phenasen® New Zealand data sheet 23 July 2019 https://www.medsafe.govt.nz/profs/datasheet/p/phenaseninj.pdf (accessed 15 July 2022).
Pharmaco (NZ) Ltd Vesanoid® New Zealand data sheet 21 April 2022 https://www.medsafe.govt.nz/profs/datasheet/v/Vesanoidcap.pdf (accessed 15 July 2022).
* The medicines, doses, combinations, and schedule in this treatment regimen have been carefully reviewed against international best practice guidelines by specialists in medical oncology around New Zealand and this advice has been accepted for publication by Te Aho o Te Kahu (the Cancer Control Agency). Sometimes medicines that are used in routine clinical practice have not been through a formal review process by the NZ Medicines Regulator Medsafe and are therefore considered unapproved or off-label. These medicines are legally able to be prescribed through sections 25 and 29 of the Medicines Act and by obtaining informed consent from patients. All treatment regimens listed on this website have been through robust peer review and are considered an accepted standard of care, whether prescribed through sections 25 or 29 or carrying formal Medsafe Approval.
s29: This symbol indicates that some formulations of the associated medicine are legally only able to be prescribed under section 29 of the Medicines Act. You can see which formulations are section 29 by hovering over the s29 symbol. You can access full medication details from the New Zealand Formulary by clicking on the medication name. Each clinician retains full responsibility for ensuring they have complied with all relevant obligations and requirements of section 29 including obtaining informed patient consent prior to prescribing the applicable medicine.