Dasatinib

Cancer Treatment

Dasatinib is a targeted therapy used to treat certain types of leukemia, a cancer of the white blood cells. It is specifically used for cancers that are Philadelphia chromosome-positive (Ph+), which means the cancer cells contain a specific genetic abnormality.

Chronic Myeloid Leukemia (CML)

In adults, dasatinib is used for:

• Newly diagnosed Ph+ CML in the chronic phase.
• Ph+ CML in any phase (chronic, accelerated, or myeloid/lymphoid blast phase) that has not responded to or cannot be treated with other medications.

In children 1 year of age and older, it is used for Ph+ CML in the chronic phase, whether it is newly diagnosed or if previous treatments were unsuccessful or not tolerated.

Acute Lymphoblastic Leukemia (ALL)

Dasatinib is also used to treat Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in specific situations:

• In adults who are resistant or intolerant to other therapies.
• In children 1 year of age and older with newly diagnosed Ph+ ALL, when used in combination with chemotherapy.

This medication works by blocking the action of an abnormal protein that signals cancer cells to multiply, which helps slow or stop the spread of the disease.

How Dasatinib Works

Dasatinib is a type of medication known as a tyrosine kinase inhibitor. It works by identifying and blocking specific proteins, called kinases, that are found in cancer cells. These proteins act as signaling molecules that tell cells when to grow and divide. In certain cancers, these proteins are overactive, leading to the uncontrolled growth of abnormal cells.

Blocking Abnormal Growth Signals

In patients with certain types of leukemia, such as chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), an abnormal genetic change creates a protein called BCR-ABL. This protein sends constant signals for the body to produce excessive amounts of white blood cells. Dasatinib binds to this protein and blocks its activity, which helps stop the production of these cancerous cells.

Targeting Multiple Pathways

Dasatinib is considered a multi-kinase inhibitor because it targets several different proteins involved in cancer progression. These include:

• BCR-ABL
• SRC family kinases
• c-KIT
• Ephrin (EPH) receptor kinases
• Platelet-derived growth factor receptor beta (PDGFRβ)

By interfering with these multiple signaling pathways, the medication helps to slow the growth of the cancer and may help the bone marrow return to normal function.

Common Side Effects

Commonly reported side effects of dasatinib include:

• Diarrhea, nausea, or stomach pain
• Headache and muscle or joint pain
• Feeling tired or weak
• Skin rash
• Fever and cough
• Swelling of the hands, feet, or face

Serious Side Effects

Dasatinib can cause serious complications. Seek medical help immediately for symptoms such as:

• Fluid retention: Shortness of breath (especially when lying down), chest pain, or rapid weight gain.
• Low blood cell counts: Increased risk of infection, fever, easy bruising, or unusual bleeding.
• Heart problems: Fast or irregular heartbeat, dizziness, or fainting.
• Bleeding issues: Blood in the stool or urine, coughing up blood, or severe headache.
• Pulmonary arterial hypertension: High blood pressure in the lungs, which may cause shortness of breath and fatigue.
• Liver problems: Yellowing of the eyes or skin, dark urine, or pain in the upper right stomach area.

This medication can also cause tumor lysis syndrome, a condition caused by the rapid breakdown of cancer cells. Your healthcare provider will monitor your blood work regularly to check for changes in blood cell counts and organ function.

Blood Cell Count Changes

Dasatinib can cause a severe decrease in the number of red blood cells, white blood cells, and platelets. This condition, known as myelosuppression, increases the risk of infection, anemia, and bleeding. Frequent blood count monitoring is required during treatment, especially during the first several months.

Fluid Retention

Patients may experience significant fluid buildup in the body. This can occur around the lungs (pleural effusion), the heart (pericardial effusion), or in the abdomen (ascites). Symptoms such as shortness of breath, a dry cough, or sudden weight gain should be reported to a healthcare provider immediately.

Cardiovascular and Pulmonary Risks

• Pulmonary Arterial Hypertension: High blood pressure in the blood vessels of the lungs can occur at any time during treatment and may be permanent if the medication is not stopped.
• Heart Rhythm: The medication may affect the heart's electrical activity, known as QT prolongation, which can lead to serious heart rhythm issues. This risk is higher in patients with low potassium or magnesium levels.
• Heart Failure: There is a risk of developing heart failure, heart attacks, or high blood pressure during therapy.

Bleeding and Skin Reactions

Serious and sometimes fatal bleeding episodes have been reported, particularly in the brain or gastrointestinal tract. This risk is often higher in patients with low platelet counts. Additionally, severe skin reactions, including Stevens-Johnson syndrome, may occur and require immediate medical attention if a rash or blisters develop.

Pregnancy and Reproduction

This medication can cause fetal harm if taken during pregnancy. Effective contraception is recommended for both men and women during treatment and for 30 days after the final dose. It is also recommended to avoid breastfeeding while taking this drug and for two weeks after the last dose.

Other Precautions

Dasatinib tablets contain lactose, which may be a concern for patients with lactose intolerance. Additionally, certain medications that reduce stomach acid, such as proton pump inhibitors or H2 blockers, can significantly decrease the absorption of dasatinib and should generally be avoided.

Pregnancy

Dasatinib can cause harm to a fetus when taken during pregnancy. Clinical reports have documented instances of birth defects and other complications in infants exposed to the medication before birth. Individuals who are able to become pregnant should undergo a pregnancy test before starting this medication to confirm they are not pregnant.

Effective contraception is recommended for both men and women during treatment. Women should continue using birth control for at least 30 days after their last dose. Men with partners who can become pregnant should also use effective contraception during treatment and for 30 days after the final dose. If pregnancy is suspected or occurs during treatment, a healthcare provider should be notified immediately.

Breastfeeding

It is currently unknown if dasatinib passes into human breast milk. Due to the risk of serious adverse reactions in a nursing child, breastfeeding is not recommended during treatment and for at least 2 weeks following the final dose. Patients should consult with their healthcare team to discuss the best way to feed their baby during this time.

Dosage Forms

Dasatinib is available in the following form:

• Oral Tablet: These are film-coated tablets intended to be swallowed whole.

This medication should not be crushed, cut, or chewed. It is currently only available as a tablet and does not come in liquid or injectable formulations.

FDA Approval and Indications

Dasatinib was approved by the U.S. Food and Drug Administration (FDA) to treat certain forms of leukemia in adults and children. Its primary indications include:

• Newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the chronic phase.
• Ph+ CML in chronic, accelerated, or blast phases for patients who no longer benefit from or cannot tolerate other treatments.
• Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in patients with resistance or intolerance to prior therapy.

In pediatric patients, it is approved for Ph+ CML in the chronic phase and for Ph+ ALL in combination with chemotherapy.

Safety Monitoring and Communications

The FDA monitors the safety profile of dasatinib through the FDA Adverse Event Reporting System (FAERS). In 2018, the FDA identified a potential signal of serious risk regarding pulmonary hypertension associated with the use of this drug. Labeling includes warnings for serious conditions such as myelosuppression, fluid retention, and cardiovascular events.

There is currently no Risk Evaluation and Mitigation Strategy (REMS) required for this medication. Generic versions of dasatinib have been approved by the FDA, providing alternatives to the brand-name version.

FDA-Approved Indications

The U.S. Food and Drug Administration (FDA) has approved dasatinib for the treatment of several conditions involving Philadelphia chromosome-positive (Ph+) cancers:

• Chronic Myeloid Leukemia (CML): It is approved for adults with newly diagnosed Ph+ CML in the chronic phase. It is also used for adults with chronic, accelerated, or blast phase Ph+ CML who are resistant to or intolerant of other therapies.
• Acute Lymphoblastic Leukemia (ALL): It is approved for adults with Ph+ ALL who have not responded to or cannot tolerate other treatments.
• Pediatric Use: The FDA has approved dasatinib for children aged one year and older who have Ph+ CML in the chronic phase or newly diagnosed Ph+ ALL when used in combination with chemotherapy.

FDA Safety Warnings

The FDA has identified several serious risks associated with dasatinib that require medical monitoring:

• Myelosuppression: This medication can cause a severe decrease in blood cell counts, including platelets, red blood cells, and white blood cells.
• Fluid Retention: Patients may experience significant fluid buildup, which can occur around the lungs, the heart, or in the abdomen.
• Cardiovascular Concerns: There is a risk of heart-related issues, including heart failure and changes in heart rhythm, such as QT prolongation.
• Pulmonary Arterial Hypertension: A rare but serious condition involving high blood pressure in the lung arteries has been reported in patients taking this drug.
• Bleeding Events: Severe and sometimes fatal bleeding has occurred in patients treated with this medication.

The FDA also warns that dasatinib can cause harm to a developing fetus. It is recommended that individuals of reproductive potential use effective contraception during treatment and for a period after the final dose.