Treatment Name: ATRA (Tretinoin) + Arsenic Trioxide (Trisenox®) Consolidation
ATRA (Tretinoin) + Arsenic Trioxide (Trisenox®) Consolidation is a Chemotherapy Regimen for Acute Promyelocytic Leukemia (APL)
How does ATRA + arsenic trioxide work?
At diagnosis, APL cells are "trapped" in an immature phase of maturation, do not function normally, and can suppress the growth of good cells in the bone marrow. Both of the medications in ATRA + arsenic trioxide are designed to reduce the number of APL cells by triggering leukemic promyelocytes to die.
ATRA = All-Trans-Retinoic-Acid = Retinoic Acid = Tretinoin
Arsenic TriOxide (Trisenox®) = ATO
Goals of therapy:
ATRA + arsenic trioxide consolidation is given after completion of induction therapy to eliminate any remaining leukemic cells for patients with low-to-intermediate risk APL. ATRA + arsenic trioxide is commonly given with the goal of cure.
How is ATRA + arsenic trioxide for APL given?
- Oral ATRA (Tretinoin) is taken by mouth in two divided doses per day, one morning dose and one night dose, each with a large glass of water for 15 consecutive days followed by 15 consecutive days off
- This equals one ATRA cycle
- Arsenic trioxide intravenous (I.V.) infusion over two hours once daily, Monday through Friday, for four consecutive weeks (20 infusions) followed by 4 consecutive weeks off
- This equals one arsenic trioxide cycle
Estimated total infusion time for this treatment:
- Up to 2 hours for each arsenic trioxide treatment
- Infusion times are based on clinical studies, but may vary depending on doctor preference or patient tolerability. Pre-medications and intravenous (I.V.) fluids, such as hydration, may add more time
During consolidation, arsenic trioxide is usually given in an outpatient infusion center, allowing the person to go home afterwards while ATRA is usually taken at home.
ATRA is taken for two consecutive weeks followed by two consecutive weeks off where ATRA is not taken, this is known as one Cycle. During consolidation, a total of seven ATRA cycles are taken. Duration of ATRA therapy may last up to seven months, depending upon response, tolerability, and number of cycles prescribed.
Arsenic trioxide is given on weekdays (Monday through Friday) for four consecutive weeks followed by four consecutive weeks off where arsenic trioxide is not given, this is known as one Cycle (8 weeks). During consolidation, a total of four arsenic trioxide cycles are given. Duration of arsenic trioxide therapy may last up to eight months, depending upon response, tolerability, and number of cycles prescribed.
Click here for the common ATRA (Tretinoin) + Arsenic Trioxide (Trisenox®) Consolidation Doses.
What are the most common side effects from ATRA + arsenic trioxide for APL?
In a multi-drug regimen, each medication has unique side effects. When these medicines are given together, drug-related side effects reported in clinical studies give the best estimate of what to expect. In clinical studies, the most commonly reported side effects of ATRA + arsenic trioxide consolidation are shown here:
A note about side effect percentages
- Liver dysfunction (63%)
- Heart rhythm abnormalities (16%)
- Intestinal toxicity (4%)
- Headache with ATRA use (exact % not reported)
- Nausea or vomiting (exact % not reported)
Roughly 1% of patients permanently discontinue treatment with ATRA + arsenic trioxide due to unacceptable side effects before finishing all recommended cycles.
Importantly, not all people who experience a side effect from ATRA + arsenic trioxide (Trisenox®) will experience it in the same way. It may be mild in some or severe in others, depending upon the individual. Everybody is different. Additionally, side effects may vary over time. For some, side effects may be a reason to delay or switch treatment, reduce the dose, or avoid future treatment with a certain medication altogether.
Side effects may be treatable when they occur or preventable by taking certain medications before they happen. When medications are taken to prevent a problem, this is known as prophylaxis, or "prophy" for short.
After starting treatment with ATRA + arsenic trioxide (Trisenox®) will experience it in the same way. It may be mild in some or severe in others, depending upon the individual. Everybody is different. Additionally, side effects may vary over time. For some, side effects may be a reason to delay or switch treatment, reduce the dose, or avoid future treatment with a certain medication altogether., be sure to come back and watch all of the side effect videos shown below. Each of these videos contain valuable information about side effect management that will hopefully help you to both feel better and stay out of the hospital.
Watch videos on common ATRA + aresenic trioxide therapy side effects below
How often is monitoring needed?
Labs (blood tests) may be checked before starting consolidation therapy then periodically during therapy at the discretion of your Doctor. Labs often include: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), PT, aPTT, fibrinogen, D-dimer, plus any others your doctor may order.
How often is imaging needed?
Imaging may be checked before treatment, and often weekly (or more). Imaging may include an electrocardiogram, commonly referred to as an ECG, or EKG. ECGs are used to evaluate the QTc interval prior to arsenic trioxide therapy and periodically throughout treatment.
How might blood test results/imaging affect treatment?
Depending upon the results, your doctor may advise to continue ATRA + arsenic trioxide as planned, reduce the dose of future treatments, delay the next dose until the side effect goes away, or switch to an alternative therapy.
What are the most important things to know about ATRA + arsenic trioxide when receiving therapy?
- ATRA (Tretinoin) may cause chapped lips or drying and cracking in the corners of the mouth, known as cheilitis. Frequenyl applying lip balm may help to decrease these symptoms
- If ATRA (Tretinoin) causes severe headaches, ask your pharmacist to try ordering a different brand (manufacturer) the next time you need a refill
- Medications that lengthen the time to make the heart beat, such as QT-prolonging medications should be minimized (used less) while receiving arsenic trioxide. Ondansetron (Zofran) use for nausea is one example of a QT-prolonging medication
- A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
- Clinical trials may exist for APL. Ask your doctor if any studies are currently enrolling in your area. If not, go to clinicaltrials.gov to search for other centers offering study medications
Patient Assistance & Co-payment Coverage
Patients under the age of 65 years, or those with private insurance plans:
If you have insurance and are looking for patient assistance or copay assistance for ATRA (Tretinoin) + Arsenic Trioxide (Trisenox®) Consolidation, we have provided links that may help.
Visit our Patient Assistance page and click the links to various patient assistance programs for help paying for ATRA (Tretinoin) + Arsenic Trioxide (Trisenox®) Consolidation. Depending upon your income, they may be able to help cover the cost of:
- Arsenic Trioxide
For Branded medications (may be available for generic medications too), check with the manufacturer to determine if a co-pay card is offered and if it could reduce your monthly copay.
- If you are uninsured, check with the manufacturer to determine if you are eligible to receive medication at no cost.
Medicare and Medicaid patients (Patients 65 years or older):
The clinic providing treatment will likely pre-authorize medications and immune therapies such as ATRA (Tretinoin) + Arsenic Trioxide (Trisenox®) Consolidation and are the best source to help you understand drug cost.
- Ask to speak with a patient assistance technician or financial counselor at the clinic or hospital administering this therapy.
What is Emotional Wellness?
Emotional wellness is having a positive outlook balanced with a realistic understanding of current life events. This requires both an awareness and acceptance of your emotions. It is with this knowledge that you can develop a plan to take the necessary actions to positively impact your life.
Emotional wellness uses an ongoing process to continually reflect on the stressors of life in a constructive manner to move forward and create happiness.
Because emotional wellness is deeply connected with physical, social, and spiritual wellness, pursuing it often becomes particularly difficult in times of major illness. Despite this difficulty, working toward emotional wellness has been connected to improved treatment outcomes and a higher likelihood of achieving goals of therapy.
Learn more about pursuing emotional wellness while receiving treatment with ATRA (Tretinoin) + Arsenic Trioxide (Trisenox®) Consolidation