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Review on the use of hydroxyurea...

While hydroxyurea is a mainstay in SCD, it’s original indication for a variety of cancers has changed over several decades. Due to the advancement of medicine, cancer is now treated with drugs that target highly specific receptors in the body. Hydroxyurea is a drug that is nonspecific in its nature, which is why it has been phased out of modern therapy due to the rise of agents such as tyrosine kinase inhibitors (i.e. imatinib, nilotinib) that have pinpoint targets based on the cancer’s pathophysiology. Currently hydroxyurea is reserved as an option in CML rather than the various cancers it was initially approved for.

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 Hydroxyurea: An Old Drug in Need of New Clinical Trials in Myeloproliferative Neoplasms

Hydroxyurea (Hu) has been a front-line therapeutic agent for myeloproliferative neoplasms (MPN) for many years and still enjoys the endorsement of experts in the field. However, several publications have reported sub-optimal response, the need for treatment interruption because of cytopenias and lack of sustained response. In all these studies, Hu was used as continuous therapy at a daily dose ranging from 500mg to 3000mg.

 Hydroxyurea—The Good, the Bad and the Ugly

Hydroxyurea (HU) is mostly referred to as an inhibitor of ribonucleotide reductase (RNR) and as the agent that is commonly used to arrest cells in the S-phase of the cycle by inducing replication stress. It is a well-known and widely used drug, one which has proved to be effective in treating chronic myeloproliferative disorders and which is considered a staple agent in sickle anemia therapy and—recently—a promising factor in preventing cognitive decline in Alzheimer’s disease.

Articles of Interest

Hydroxyurea for sickle cell disease

Exactly how hydroxyurea works in sickle cell is not known. Evidence suggests that the therapy can increase levels of fetal hemoglobin, which is an alternative version of hemoglobin that is normally made in early fetal development, but stops being produced shortly after birth. By increasing the levels of fetal hemoglobin, which is more effective at transporting oxygen through the body than its adult counterpart, hydroxyurea may help counteract the effects of the mutated adult version of the protein. In patients, it works to reduce red blood cell sickling and destruction, lowering the frequency of painful crises, and the need for blood transfusions.

Hydroxyurea therapy for sickle cell anemia

Sickle cell anemia (SCA) is a severe, inherited hemoglobin disorder affecting 100,000 persons in the US and millions worldwide. Hydroxyurea, a once daily oral medication, has emerged as the primary disease-modifying therapy for SCA. The accumulated body of evidence over 30 years demonstrates that hydroxyurea is a safe and effective therapy for SCA, but hydroxyurea remains underutilized for a variety of reasons.

Hydroxyurea Therapy Found Effective for Myeloproliferative Neoplasms

Patients with myeloproliferative neoplasms (MPN) with essential thrombocythemia (ET) or polycythemia vera (PV) were found to benefit from hydroxyurea therapy.

Hydroxyurea Toxicity

Hydroxyurea is an antineoplastic agent used alone or in combination with other chemotherapeutic drugs or radiation in the treatment of resistant leukemias and carcinomas of the head and neck. It is also used to increase fetal hemoglobin concentration, thus reducing the frequency of severe crisis and reducing the necessity for blood transfusions in patients with sickle cell anemia. Despite its utility, hydroxyurea is an extremely toxic drug with a low therapeutic index.

The Current Role of Hydroxyurea in the Treatment of Sickle Cell Anemia

Despite advancements in treatment of sickle cell disease (SCD), hydroxyurea, a ribonucleotide reductase inhibitor, remains the cornerstone of therapy. While its primary effect is the elevation of fetal hemoglobin (HbF), hydroxyurea’s mechanisms of action are multifaceted.

The modern use of hydroxyurea for children with sickle cell anemia

Over the past 40 years, the introduction and refinement of hydroxyurea therapy has led to remarkable progress in the care of individuals with sickle cell anemia (SCA). From initial small proof-of-principle studies to multicenter phase III controlled clinical trials and then numerous open-label studies, the consistent benefits of once-daily oral hydroxyurea have been demonstrated across the lifespan

The Truth About Hydroxyurea

To answer your question, hydroxyurea is still the preferred treatment for PV and ET in the treatment guidelines, and is considered the gold standard. In 2023, they (ASH) added Besremi interferon as an additional preferred treatment for PV. Members need to keep in mind that everyone is different. There's no cookie cutter solution to MPNs. It may seem that way because unlike most diseases, we only have 3 medication "choices" right now. Keep in mind that not everyone can (A) afford or get insurance approval for interferons or Jakafi, and/or (B) tolerate interferons or Jakafi.

What Is Cytoreductive Therapy in MPNs?

Hydroxyurea decreases the number of blood cells that your bone marrow produces. Because it affects all types of blood cells, it is generally useful for all types of MPNs. Available in capsule form, hydroxyurea is a chemotherapy medication, but it is usually taken at low doses to treat MPNs. Its side effects are generally mild. Because hydroxyurea reduces the production of all blood cells, it can cause too-low levels of some blood cell types.

Why I Don’t Take Hydroxyurea

Developed originally as a chemotherapy drug, Hydrea has the potential of preventing crises by actually killing off the neoplastic ‘sickle cells’ and prevents the developed ones from taking the sickle cell shape. Since it’s the clumping of the shape that causes a crises, it’s been known to reduce crises’ by as much as 50%. Except it’s a cancer drug. It’s a cancer drug. Ick, ick ick! That alone comes with it’s own list of complications. The list is so long it’s atrocious to call it a medicine.

Resources

Hydroxycarbamide

This drug lowers the number of blood cells produced by your bone marrow. Hydroxycarbamide (formerly known as hydroxyurea) goes under the brand name Hydrea® and is a very common treatment for all myeloproliferative neoplasms (MPNs). Hydroxycarbamide comes as a capsule and is taken orally. Most people who take the drug in low doses find that they don’t have too many side effects.