From the Guidelines
The main adverse reactions of pemetrexed include bone marrow suppression, fatigue, nausea, vomiting, diarrhea, and stomatitis, as evidenced by a randomized phase III trial in first-line treatment of malignant pleural mesothelioma 1. These adverse reactions are significant and can impact the patient's quality of life.
- Bone marrow suppression can manifest as neutropenia, thrombocytopenia, and anemia, which can increase the risk of infections and bleeding complications.
- Fatigue, nausea, vomiting, diarrhea, and stomatitis can also have a significant impact on the patient's daily life and overall well-being. To minimize these side effects, patients should receive vitamin supplementation with folic acid and vitamin B12, as well as dexamethasone to reduce the severity of skin reactions 1. Regular monitoring of complete blood counts, renal and hepatic function is essential during treatment to quickly identify and manage any adverse reactions. Pemetrexed's toxicity profile relates to its mechanism as an antifolate that inhibits multiple enzymes involved in folate metabolism, disrupting DNA and RNA synthesis in rapidly dividing cells, which affects not only cancer cells but also normal tissues with high cell turnover rates. The incidence of these adverse reactions can be reduced with appropriate supportive care and monitoring, allowing patients to tolerate the treatment and achieve the best possible outcomes in terms of morbidity, mortality, and quality of life.
From the Research
Main Adverse Reactions of Pemetrexed
The main adverse reactions of pemetrexed include:
- Myelosuppression, predominantly neutropenia 2, 3
- Fatigue 2, 3
- Leucopenia 2, 3
- Nausea 2, 3
- Dyspnea 3
- Vomiting 2, 3
- Chest pain 3
- Anemia 3
- Thrombocytopenia 3
- Anorexia 3
- Diarrhea 4, 5
- Rash 4, 5
- Febrile neutropenia 4
- Angina 2
- Myocardial infarction 2
- Stroke 2
- Liver damage 2
- Bullous skin rash 2
Reduction of Adverse Reactions
Supplementation with folic acid and vitamin B12 can reduce the haematological and gastrointestinal complications associated with the antifolate activity of pemetrexed 2, 6. The administration of vitamin B12 and folic acid for 7 days prior to the administration of the first dose of pemetrexed is recommended, but a retrospective study suggested that patients could be safely treated with pemetrexed if vitamin supplementation is initiated for less than 7 days prior to the first administration of pemetrexed 5.
Monitoring and Management
Patients receiving pemetrexed must be monitored closely for some rare but potentially severe adverse effects 2. The summary of product characteristics (SPC) recommends that pemetrexed therapy must be administered in combination with folic acid and vitamin B12 supplementation to reduce haematological toxicity, and also with corticosteroid therapy to reduce the risk of serious skin reactions 2.