Tretinoin (ATRA, all-trans retinoic acid) — Drug Monograph
Brand names: Vesanoid
Drug class: Other
Mechanism of Action
A naturally occurring retinoid (all-trans retinoic acid) that binds retinoic acid receptors (RAR). In acute promyelocytic leukemia (APL), the PML-RARα fusion protein blocks myeloid differentiation; pharmacologic ATRA overcomes this block, inducing terminal differentiation and apoptosis of the leukemic promyelocytes rather than directly killing them. This differentiating effect underlies both its efficacy and the risk of differentiation syndrome.
FDA Indications
- Acute promyelocytic leukemia (APL, FAB M3) — induction of remission in patients with t(15;17) and/or PML-RARα, refractory to or relapsed after anthracycline chemotherapy, or when anthracyclines are contraindicated
Common Side Effects
- Headache
- Dry skin and mucosal dryness
- Cheilitis
- Rash/pruritus
- Bone pain
- Nausea/vomiting
- Fatigue
- Elevated triglycerides/cholesterol
Clinical Pearl
ATRA works by differentiating malignant promyelocytes rather than by cytotoxicity, which is why differentiation syndrome (fever, dyspnea, pulmonary infiltrates, edema, hypotension) is its signature emergency — treat empirically with dexamethasone at the first suspicion rather than waiting for confirmation. Combined with arsenic trioxide, ATRA enables chemotherapy-free cure in low/intermediate-risk APL. Start ATRA immediately when APL is suspected to counter the deadly coagulopathy.