High-dose methotrexate is a key treatment for brain cancer caused by lymphoma. It helps get into the brain where the cancer cells are hiding and can help cure it. In the UK, doctors often use high-dose methotrexate as part of a combination treatment to make it more effective.
This is especially important because brain lymphoma is a tough type of cancer that needs strong treatment.
High-dose methotrexate (HDMTX) is indicated for patients with primary central nervous system lymphoma (PCNSL) and for CNS prophylaxis in high-risk non-Hodgkin lymphoma (NHL) patients.
Advanced Disease: Stage III or IV disease.
Age: Patients older than 60 years.
Elevated Serum LDH: Levels greater than three times the upper limit of normal.
Performance Status: WHO/ECOG performance status greater than 1.
Multiple Extranodal Sites: Involvement of two or more extranodal sites, including testes, breast, renal, or adrenal involvement.
Histologic Subtype: Aggressive subtypes such as diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, and double-hit lymphomas (HGBL-DH).
MYC and BCL2/BCL6 Rearrangements: Presence of these genetic alterations.
Extranodal Involvement: Lymphoma in the testes, sinuses, breasts, lymph nodes in the pelvis, or bone marrow.
Renal Function: Adequate renal function with a creatinine clearance of at least 50 ml/min.
Liver Function: Normal liver function tests or mild abnormalities that do not contraindicate treatment.
Absence of Fluid Compartments: No pleural effusion, ascites, or significant edema.
Tumor Lysis Syndrome Risk: Assessment and management of tumor lysis syndrome risk.
Medication History: No recent use of medications that increase the risk of methotrexate toxicity, such as co-trimoxazole, NSAIDs, or penicillin antibiotics.
Fertility Considerations: Counseling on potential infertility risks and fertility preservation options.
Pregnancy: Negative pregnancy test for women of child-bearing age.
Informed Consent: Patient must provide informed consent after receiving adequate information about the treatment and potential side effects.
These criteria ensure that high-dose methotrexate is used safely and effectively in patients with CNS lymphoma or those at high risk of CNS involvement.
Before administering high-dose methotrexate, the following pre-assessment steps are necessary:
Blood Tests: Complete blood count (FBC), liver function tests (LFTs), creatinine, urate, calcium, magnesium, glucose, hepatitis B core antibody, hepatitis B surface antigen, hepatitis C antibody, and group and save.
Renal Function Assessment: Assess creatinine clearance and consider measured glomerular filtration rate (GFR) using methods such as 51Cr-EDTA or 99mTc-DTPA, especially in patients over 65 years or with significant comorbidities.
Medication History: Confirm the patient’s medication history, ensuring they have not taken co-trimoxazole, NSAIDs, or penicillin antibiotics in the week before the infusion due to increased risk of renal toxicity.
ECG and Echocardiogram: Perform an ECG and possibly an echocardiogram if clinically indicated.
Performance Status: Record the patient’s performance status using WHO/ECOG criteria.
Height and Weight: Measure the patient’s height and weight.
Consent: Ensure the patient has received adequate verbal and written information regarding their disease, treatment, and potential side effects, and obtain written consent on the day of treatment.
Fertility Counseling: Discuss the potential risk of infertility with the patient and offer fertility advice.
Pleural Effusion and Ascites Assessment: Assess for any pathologic fluid accumulation that could lead to prolonged methotrexate plasma elimination and unexpected toxicity.
Tumor Lysis Syndrome Risk Assessment: Refer to the Tumor Lysis Syndrome in Adults protocol.
Pregnancy Test: Conduct a urine pregnancy test before cycle 1 of each chemotherapy course for women of child-bearing age unless they are post-menopausal, have been sterilized, or undergone a hysterectomy.
These steps are crucial to ensure the safe and effective administration of high-dose methotrexate.
Pre-treatment Assessment: Perform a complete blood count (CBC), liver function tests (LFTs), renal function tests, and a pregnancy test for women of childbearing age.
Hydration: Administer intravenous (IV) fluids to ensure adequate hydration before and during methotrexate administration.
Folate Rescue: Administer leucovorin (folinic acid) to reduce methotrexate toxicity.
Methotrexate Administration: Administer high-dose methotrexate IV over 4 hours. Dosage varies but can be up to 12 grams/m².
Urine Alkalinization: Maintain urine pH between 7.0 and 8.0 to prevent crystallization of methotrexate in the renal tubules.
Monitoring: Regularly monitor CBC, LFTs, renal function, and methotrexate levels in the blood.
Toxicity Management: Monitor for signs of toxicity and manage accordingly. Administer medications to manage side effects as needed.
Post-treatment Care: Continue monitoring and supportive care until methotrexate levels are below a safe threshold.
Potential Side Effects of High-Dose Methotrexate:
Sensitivity to sunlight: Skin may become very sensitive to sunlight, causing reactions similar to sunburn.
Loss of appetite: Reduced desire to eat.
Nausea and vomiting: Feeling or being sick.
Stomach pain or indigestion: Discomfort in the stomach.
Diarrhea: Frequent loose or watery stools.
Headaches: Persistent or severe headaches.
Tiredness or drowsiness: Feeling unusually tired or drowsy.
Hair loss: Potential hair thinning or loss.
Liver or lung problems: Increased risk of liver or lung issues.
Renal damage: Risk of kidney damage due to methotrexate and its metabolites.
Management Strategies to Mitigate These Effects:
Sensitivity to sunlight: Stay out of bright sun, use high factor sunscreen (SPF 30 or above), and wear protective clothing.
Loss of appetite: Eat smaller meals more often, and have nutritious snacks high in calories and protein.
Nausea and vomiting: Eat simple meals, avoid rich or spicy foods, and take small, frequent sips of water to avoid dehydration.
Stomach pain or indigestion: Rest and relax, eat and drink slowly, have smaller and more frequent meals, and use a heat pad or covered hot water bottle for stomach ache.
Diarrhea: Drink lots of fluids, such as water or squash, and avoid taking other medicines to treat diarrhea without consulting a doctor.
Headaches: Rest and drink plenty of water, avoid alcohol and NSAIDs, and use paracetamol for pain relief.
Tiredness or drowsiness: Do not drive, cycle, or use machinery if feeling tired or drowsy, and speak to a doctor if this does not improve.
Hair loss: Consult a doctor who may lower the dose or recommend a different medication.
Liver or lung problems: Regular monitoring and check-ups with a doctor to detect any issues early.
Renal damage: Ensure adequate hydration, monitor urine output and pH, and avoid NSAIDs and penicillin antibiotics before and during treatment.
High-dose methotrexate is a crucial component of CNS lymphoma treatment, but it requires careful administration to minimize side effects and ensure efficacy.
The NHS protocol emphasizes the importance of hydration, folate rescue, urine alkalinization, and regular monitoring to prevent toxicity.
Before administering high-dose methotrexate, patients should undergo pregnancy testing, have their blood pressure checked, and receive a thorough explanation of potential side effects.
During treatment, patients should be closely monitored for signs of toxicity, including:
To mitigate these effects, patients can take various management strategies, such as:
Regular monitoring and check-ups with a doctor are crucial to detect any issues early, particularly liver or lung problems and renal damage.
Patients should also be aware of potential long-term side effects, such as infertility and increased risk of infections, and take necessary precautions to prevent them.
In conclusion, high-dose methotrexate is a complex treatment that requires careful administration and close monitoring to ensure its effectiveness while minimizing side effects. By following the NHS protocol and taking proactive steps to manage potential side effects, patients can receive optimal care for CNS lymphoma.