Pralatrexate is a chemotherapy medication used to treat certain types of cancer. It is classified as an antifolate, meaning it interferes with the body’s use of folic acid in cellular processes. This drug targets rapidly growing cells, a characteristic of cancer, to slow or stop disease progression.
Medical Uses for Pralatrexate
Pralatrexate is approved for treating adult patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). PTCL is a diverse group of fast-growing non-Hodgkin lymphomas that affect T-cells, a type of white blood cell. This condition can manifest in lymph nodes, other organs, or spread throughout the body.
Relapsed and refractory describe specific situations in cancer treatment. Relapsed cancer means the disease returned after remission, where initial treatments were successful. Refractory cancer indicates the disease did not respond to initial therapy or worsened despite treatment. Pralatrexate is used in cases where patients have already undergone at least one prior therapy for their PTCL.
Mechanism of Action
Pralatrexate operates as an antifolate, interfering with the metabolic pathways cancer cells rely on for growth and division. Cancer cells, due to their rapid replication, require significant amounts of folate to synthesize DNA, RNA, and proteins. This drug works by targeting an enzyme called dihydrofolate reductase (DHFR).
DHFR converts dihydrofolate into tetrahydrofolate, a form of folate necessary for producing nucleotide precursors, the building blocks of DNA and RNA. By blocking DHFR, pralatrexate effectively depletes these essential precursors within cancer cells. This disruption inhibits the synthesis of DNA, RNA, and proteins, leading to the death of rapidly dividing cancer cells.
The drug also has a high affinity for reduced folate carrier-1 (RFC-1), a protein often overexpressed on the surface of many cancer cells. This affinity allows pralatrexate to enter and accumulate more efficiently within malignant cells. Once inside, pralatrexate undergoes polyglutamation, a process that helps trap the drug within the cell and prolong its inhibitory effects on folate-dependent enzymes.
Administration and Dosing
Pralatrexate is administered intravenously (IV) as an infusion in a hospital or clinic setting under healthcare professional supervision. The drug is usually given once a week for six consecutive weeks, followed by a one-week rest period, forming a seven-week treatment cycle. This cycle continues until the disease progresses or unacceptable side effects occur.
Each dose is given as a rapid intravenous push over three to five minutes. To protect healthy cells and reduce certain side effects, patients receiving pralatrexate must also take vitamin supplements. This includes oral folic acid, 1 to 1.25 milligrams daily, starting at least 10 days before the first pralatrexate dose and continuing for 30 days after the last dose.
Patients also receive an intramuscular injection of vitamin B12, 1 milligram, within 10 weeks prior to the initial pralatrexate dose. Subsequent vitamin B12 injections are given every 8 to 10 weeks thereafter, and these can be administered on the same day as the pralatrexate treatment. This supplementation helps minimize potential hematologic and mucosal toxicities.
Potential Side Effects
Pralatrexate, like other chemotherapy agents, can cause various side effects, ranging from common to serious. Common side effects include mucositis, inflammation and sores in the mouth and digestive tract, potentially causing difficulty swallowing or eating. Fatigue is also common, along with nausea.
The drug can also lead to myelosuppression, a reduction in bone marrow activity, leading to lower blood cell counts. This includes thrombocytopenia (a decrease in platelets), which can cause easy bruising or bleeding. Patients may also experience anemia (a reduction in red blood cells), leading to tiredness and weakness, and neutropenia (a decrease in white blood cells), increasing susceptibility to infections.
More serious side effects require immediate medical evaluation. These can include:
Severe skin reactions, such as blistering, peeling, or widespread rashes, which may indicate conditions like Stevens-Johnson syndrome or toxic epidermal necrolysis.
Signs of infection, such as fever, chills, persistent cough, or a sore throat.
Unusual bleeding or bruising, including black or tarry stools, blood in urine, or pinpoint red spots on the skin.
Shortness of breath.
New or worsening liver problems, indicated by yellowing of the skin or eyes (jaundice), dark urine, or upper right abdominal pain.
Changes in kidney function, such as decreased urine output or swelling in the legs.
Important Patient Precautions
Before starting pralatrexate treatment, patients should provide their healthcare team with a complete list of all medications, including prescription drugs, over-the-counter medicines, and herbal supplements. Certain drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, or antibiotics containing trimethoprim/sulfamethoxazole, can affect how the body processes pralatrexate, potentially leading to increased drug levels and toxicity. The gout medication probenecid can also delay the clearance of pralatrexate from the body.
Regular monitoring through blood tests is a routine part of treatment to ensure safety and adjust dosing as needed. These tests include checking blood cell counts (platelets and neutrophils) and assessing liver and kidney function. Before each dose, blood count levels and the severity of any mucositis are evaluated to determine if treatment can proceed or if a dose adjustment is necessary.
Pralatrexate can cause harm to an unborn baby. Women who are pregnant or planning to become pregnant should not use this medication. Women of childbearing potential should use effective birth control during treatment and for at least six months after the last dose.
Men with female partners who could become pregnant should also use effective contraception for at least three months following their last dose. The drug is not recommended for use during breastfeeding. Patients should also discuss any pre-existing kidney or liver conditions with their doctor, as impaired organ function may increase the drug’s exposure and potential for side effects.