Main Research Findings

Etoposide is a powerful chemotherapy drug used to treat various cancers, including small cell lung cancer, Hodgkin's lymphoma, and testicular germ cell tumors. 9 reports that etoposide can cause infusion-related reactions in pediatric patients. 19 found that intra-CSF administration of etoposide can be effective in treating relapsed/refractory CNS tumors in children and young adults, but it is associated with neurological side effects. 18 found that etoposide can be used to treat hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) effectively. These conditions are characterized by excessive inflammation, and etoposide helps by dampening the inflammatory response.

Reasons for Side Effects

Etoposide works by interfering with the DNA replication process of cancer cells, preventing them from multiplying and causing cell death. This mechanism also affects healthy cells, leading to side effects. 8 suggests that etoposide can induce various types of cell death, including apoptosis, necroptosis, and pyroptosis. These different pathways of cell death might explain some of the side effects observed with etoposide.

Common Side Effects

Myelosuppression

A common side effect of etoposide is myelosuppression, meaning it can suppress bone marrow function, leading to a decrease in blood cell production. 3 found that chronic daily administration of etoposide caused a reduction in white blood cells. This can increase the risk of infections, anemia, and bleeding.

Liver Injury

Etoposide can also affect the liver. While 3 did not observe liver injury in their study, other research, such as 11 , suggests that etoposide might contribute to liver injury in children.

Kidney Injury

Etoposide can also cause kidney problems. 4 reported increased levels of BUN and creatinine, indicating kidney damage, in patients receiving chemotherapy with etoposide and cisplatin. 2 found that combining etoposide with ifosfamide reduced nephrotoxic side effects compared to chemotherapy regimens containing cisplatin.

Cardiotoxicity

Etoposide can have a negative impact on the heart. 13 describes a case where a Hodgkin's lymphoma patient developed complete heart block after receiving doxorubicin and switched to etoposide + bleomycin + vinblastine + dacarbazine (EBVD) as a result. 4 also found instances of angina pectoris and supraventricular premature contractions in lung cancer patients who received etoposide and cisplatin.

Pulmonary Toxicity

Etoposide can also affect the lungs. 17 mentioned that the ABVD protocol (doxorubicin, bleomycin, vinblastine, dacarbazine) for Hodgkin's lymphoma carries a risk of lung toxicity due to bleomycin, and etoposide might contribute to lung toxicity as well.

Skin Toxicity

Etoposide can cause skin-related side effects. 1 suggested that the formulation of etoposide (VP16 or etoposide phosphate) might impact the severity of skin toxicity. Common side effects include hair loss, rash, and dry skin.

Gastrointestinal Side Effects

Etoposide can cause various gastrointestinal problems. 3 observed nausea and loss of appetite in patients receiving oral etoposide. Other common symptoms include nausea, vomiting, diarrhea, and constipation.

Neurotoxicity

Etoposide can affect the nervous system. 19 reported neurological side effects in children and young adults receiving intrathecal etoposide. Other potential symptoms include headaches, dizziness, numbness, and weakness.

Other Side Effects

In addition to the common side effects listed above, etoposide can cause various other adverse reactions. 6 described a case of aortitis (inflammation of the aorta) in a small cell lung cancer patient receiving pegfilgrastim, a drug often used alongside chemotherapy. compared the effectiveness and side effects of ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin) and DICE (ifosfamide, carboplatin, etoposide, and dexamethasone) for treating relapsed or refractory diffuse large B-cell lymphoma.

Countermeasures Against Side Effects

Countermeasures Against Myelosuppression

To manage myelosuppression, doctors might administer hematopoietic factors like granulocyte colony-stimulating factor (G-CSF) or erythropoietin. These factors stimulate the bone marrow to produce more blood cells.

Countermeasures Against Liver Injury

Liver function tests are regularly performed to monitor for liver damage. The dosage of etoposide might be adjusted, or the treatment could be stopped if necessary. Hepatoprotective drugs might be used concurrently to protect the liver.

Countermeasures Against Kidney Injury

Kidney function tests are regularly conducted to monitor for kidney damage. The dosage of etoposide may be adjusted, or the treatment may be stopped as needed. Staying hydrated is crucial to reduce the burden on the kidneys.

Countermeasures Against Cardiotoxicity

Cardiotoxicity is monitored through regular heart function tests. The dosage of etoposide might be adjusted, or the treatment may be stopped if needed. Cardioprotective medications might be prescribed alongside etoposide.

Countermeasures Against Pulmonary Toxicity

Lung function tests are performed regularly to monitor for pulmonary toxicity. The dosage of etoposide might be adjusted, or the treatment may be stopped as needed. Pulmonary protective drugs might be used to protect the lungs.

Countermeasures Against Skin Toxicity

To manage skin toxicity, moisturizing lotions and sunscreen are recommended. If the symptoms are severe, steroid ointments or other topical medications might be applied.

Countermeasures Against Gastrointestinal Side Effects

To manage gastrointestinal side effects, antiemetics (anti-nausea drugs) and antidiarrheal medications might be prescribed. Eating a diet of easy-to-digest foods is also recommended.

Countermeasures Against Neurotoxicity

Managing neurotoxicity involves administering appropriate medications and providing rehabilitation therapy as needed, depending on the symptoms.

Comparison Between Studies

Commonalities Between Studies

Several studies highlight that etoposide can cause various side effects, and these effects can vary in severity and frequency depending on the individual patient.

Differences Between Studies

The differences in study design, dosage, and the use of other medications alongside etoposide contribute to variations in reported side effects. For instance, 9 observed infusion-related reactions in pediatric patients receiving etoposide, while 3 didn't report such reactions in their study. It's important to consider these variations when interpreting research findings.

Cautions for Application in Daily Life

While etoposide is a powerful anti-cancer drug, it's crucial to understand that it carries a risk of side effects. Patients receiving etoposide treatment should strictly follow their doctor's instructions, undergo regular checkups, and be prepared to address any side effects that might arise.

Limitations of Current Research

There's still much to learn about the side effects of etoposide, particularly regarding the mechanisms involved and individual differences in response. Further research is needed to address these gaps and improve the safety of etoposide treatment.

Directions for Future Research

Ongoing research is needed to find ways to minimize etoposide's side effects. Important areas of focus include understanding the mechanisms behind side effects, developing biomarkers to predict side effects, and exploring new medications that could prevent or treat side effects.

Conclusion

Etoposide is a valuable drug for treating various cancers, but it's crucial to be aware of its potential side effects. Following a doctor's instructions carefully, undergoing regular checkups, and being prepared for possible side effects are essential for patients receiving etoposide treatment. Continued research is expected to improve our understanding of etoposide's side effects and lead to safer and more effective treatment approaches.