fotemustine

Action and Spectrum

Actions and Spectrum: 

• Alkylating Agent: fotemustine is an alkylating agent that adds alkyl groups (methyl or ethyl groups) to DNA molecules. This disrupts the DNA structure and interferes with the replication and transcription processes, ultimately leading to cell death. 
• DNA Crosslinking: fotemustine can form covalent bonds (crosslinks) between DNA strands, which prevents the DNA from unwinding and inhibits its ability to function correctly. This crosslinking interferes with DNA replication and repair. 
• Cell Cycle Arrest: By damaging DNA, fotemustine can trigger cell cycle arrest, preventing cancer cells from progressing through the cell cycle and dividing.  
• Spectrum of Activity: fotemustine is primarily used in treating brain tumors, including glioblastoma multiforme, anaplastic astrocytoma, and other malignant gliomas.  
• Limited Systemic Toxicity: fotemustine’s limited systemic toxicity makes it suitable for intravenous administration. This minimizes side effects in tissues and organs outside the central nervous system. 
• Chemoresistance: Like many chemotherapy drugs, resistance can develop over time with fotemustine treatment. Cancer cells may develop mechanisms to repair the DNA damage caused by the drug or resist its effects. 
• Combination Therapy: fotemustine is often used with other chemotherapy agents or radiation therapy to enhance its effectiveness in treating brain tumors. 
• Adverse Effects: Common side effects of fotemustine can include myelosuppression (reduced blood cell production), nausea, vomiting, and fatigue. Because it primarily targets rapidly dividing cells. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Extravasation 

Gastrointestinal toxicity 

Hematologic toxicity 

Bone marrow suppression 

Increased transaminase 

Pancytopenia 

Nausea 

Fever 

Injection site reactions 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindications: 

• Hypersensitivity 
• Severe bone marrow suppression 

Cautions: 

• Renal impairment 
• Hepatic impairment 
• Pregnancy  
• Breastfeeding 
• Immunosuppression 
• Neurological disorders 
• Prior radiation therapy 
• Other medications 

Pregnancy / Lactation

Pregnancy consideration:  

Pregnancy Category: D 

Breastfeeding warnings:  

It is unknown whether the drug is excreted in breast milk. Breastfeeding is not recommended during chemotherapy. 

Pregnancy category: 

Category A: Well-controlled and satisfactory studies show no risk to the fetus in the initial or later trimester. 

Category B: There was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: There was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence, these categories of drugs need to be avoided by pregnant women.    

Category N: No data is available for the drug under this category. 

Pharmacology

Pharmacology:  

• Alkylating Agent: fotemustine is classified as an alkylating agent. It adds alkyl groups (methyl or ethyl groups) to various cellular components, including DNA. This alkylation interferes with DNA’s standard structure and function, ultimately leading to DNA damage and preventing cancer cells from dividing and replicating. 
• DNA Crosslinking: One of the critical actions of fotemustine is the formation of covalent bonds (crosslinks) between strands of DNA. These crosslinks disrupt the DNA double helix and prevent it from unwinding and replicating correctly. This interference with DNA replication and transcription contributes to the drug’s anti-cancer effects. 

Pharmacodynamics: 

• Antiplatelet Activity: Some studies suggest that eugenol may have antiplatelet effects, which means it can inhibit the aggregation of blood platelets. This property could potentially reduce the risk of blood clot formation. 
• Cardiovascular Effects: Eugenol has been studied for its potential cardiovascular benefits, including its ability to relax blood vessels (vasodilation) and reduce blood pressure. However, more research is needed in this area. 
• Gastrointestinal Effects: Eugenol may have gastroprotective effects on the stomach lining and could help protect against gastric ulcers. It is also used in traditional medicine for digestive complaints. 
• Neuroprotective Effects: Some research suggests that eugenol may have neuroprotective properties and could play a role in protecting nerve cells from damage. This potential is being explored in the context of neurodegenerative diseases. 
• Anti-Cancer Properties: Some evidence suggests that eugenol may induce apoptosis (cell death) and hampers the growth of cancer cells in a few types of cancer. However, more research is needed to understand its anti-cancer potential fully. 

Pharmacokinetics: 

Absorption 

fotemustine is administered intravenously, typically as an infusion. This method ensures rapid and complete absorption into the bloodstream. 

Distribution 

fotemustine can cross the blood-brain barrier, making it particularly effective in treating brain tumors, including glioblastoma multiforme. It can penetrate the CNS, targeting cancer cells in the brain. 

Metabolism 

fotemustine undergoes metabolic conversion in the liver to its active form. The exact metabolic pathways and enzymes involved may vary among individuals. 

Elimination and Excretion 

It is important to note that dose adjustments are required for patients with kidney function impairment. 

Adminstartion

Administration: 

fotemustine is typically administered as an intravenous (IV) infusion, delivering it directly into the bloodstream through a vein. Healthcare professionals closely monitor patients during the infusion for any adverse reactions or side effects. Vital signs, including heart rate, BP, and oxygen saturation, are often monitored. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: fotemustine 

Why do we use fotemustine? 

fotemustine is a chemotherapy drug primarily used to treat certain types of brain tumors, particularly malignant gliomas like glioblastoma multiforme. Its use is mainly indicated for the following reasons: 

• Treatment of Brain Tumors: fotemustine is particularly effective in treating brain tumors because it can cross the blood-brain barrier. This barrier normally protects the brain from harmful substances in the bloodstream, but it can also limit the delivery of medications to the brain. fotemustine’s ability to penetrate this barrier allows it to target cancer cells within the central nervous system. 
• Glioblastoma Multiforme: Glioblastoma multiforme is one of adults’ most antagonistic and common types of brain tumors. fotemustine is often used as a component of chemotherapy regimens to help slow the growth of GBM and extend survival. It can be used in both newly diagnosed GBM and recurrent cases. 
• Anaplastic Astrocytoma: fotemustine may also be used to treat anaplastic astrocytoma, a less aggressive but still malignant brain tumor. It can be used as a part of multimodal therapy, including surgery and radiation therapy. 
• Alkylating Agent: fotemustine belongs to the alkylating agent class of chemotherapy drugs. Alkylating agents work by interfering with the DNA inside cancer cells, ultimately preventing their ability to divide and grow. This action mechanism effectively targets rapidly dividing cancer cells, which is a hallmark of many cancers.