Pemetrexed was approved for marketing by the FDA as early as 2004 and has been available in China for many years. As an “old” chemotherapy drug, it is not yet indicated for breast cancer.
While pemetrexed is not indicated for breast cancer, there have been many attempts and explorations by researchers, and this article will focus on the use of pemetrexed in advanced breast cancer, especially in patients with breast cancer who have failed multiple therapies.
How does pemetrexed kill cancer cells?
Pemetrexed is an anti-folate agent. Some parts of cell replication are dependent on folic acid, and pemetrexed works to inhibit cell replication by disrupting these folic acid-dependent metabolic processes, and is ultimately a cytotoxic drug.
Pemetrexed requires conversion to the active form to exert its cytotoxic effects, which occurs more readily in cancer cells than in normal cells, so pemetrexed is more active in cancer cells and has a longer duration of action.
This property of pemetrexed allows it to kill cancer cells while reducing the impact on normal cells. Pemetrexed is multitargeted, more active, and theoretically less prone to resistance.
How does pemetrexed work in advanced breast cancer?
Metastatic breast cancer
A comprehensive analysis of 10 studies related to pemetrexed in the treatment of breast cancer found remission rates of more than 30% in advanced patients treated with pemetrexed-containing regimens in the first line and about 14% in the second line. The comparison of the two data suggests that the role of first-line treatment with pemetrexed may be greater.
One study selected 31 patients with metastatic breast cancer, all previously treated with anthracyclines and paclitaxel. The remission rate after enrollment on pemetrexed monotherapy was 26%, with a median survival of nearly 13 months, and patients tolerated well while on the drug.
Analysis of 1002 patients with metastatic breast cancer showed remission rates of 8% to 31% with pemetrexed monotherapy and remission rates of 15.8% to 55.7% with pemetrexed combination therapy. Some reports from China have found that disease control rates with pemetrexed combined with chemotherapy drugs such as cyclophosphamide and capecitabine are usually more than 50%.
Refractory advanced breast cancer
It has been suggested that in refractory advanced breast cancer, pemetrexed combined with platinum-based chemotherapy can be used to achieve some efficacy with milder adverse effects. When compared with vincristine in combination with cisplatin, pemetrexed in combination with cisplatin has a higher rate of complete remission, and the use of pemetrexed for advanced breast cancer may be beneficial in improving quality of life.
Summary
While pemetrexed does not currently have an indication for breast cancer, it has shown some therapeutic value in some advanced breast cancers: both first- and second-line dosing has been attempted, with remission rates of up to more than 50% in combination with other agents.
Pemetrexed treatment may have adverse effects such as allergy, renal insufficiency, gastrointestinal bleeding, and rash, which are also issues to consider when choosing this drug.
We also need more large randomized controlled clinical studies to validate the effectiveness of pemetrexed in the treatment of advanced breast cancer.