Main Research Findings

A systematic review of six clinical trials showed that folic acid or folinic acid supplementation reduced the occurrence of gastrointestinal side effects, liver dysfunction, and discontinuation of methotrexate treatment in patients with rheumatoid arthritis receiving methotrexate therapy. 1

Infigratinib, a selective inhibitor of fibroblast growth factor receptor 2 (FGFR2), has shown promise as a treatment for cholangiocarcinoma with FGFR2 gene fusions or rearrangements. While infigratinib has a favorable side effect profile, particularly with regard to gastrointestinal side effects, its overall response rate and median overall survival were lower compared to other FGFR inhibitors like futibatinib and pemigatinib. 2

FGFR inhibitors, including infigratinib, futibatinib, and pemigatinib, have been approved by the FDA for the treatment of locally advanced or metastatic cholangiocarcinoma with FGFR2 gene mutations. However, resistance mechanisms and side effect profiles may limit their clinical utility. 3

Reasons for Side Effects

FGFR inhibitors target the FGFR signaling pathway, which is crucial for cell growth and development. While they aim to inhibit cancer cell growth, these drugs can also affect normal cells, leading to side effects. 3

Common Side Effects

Gastrointestinal Side Effects

Infigratinib has a relatively minimal side effect profile, particularly in terms of gastrointestinal side effects, compared to other FGFR inhibitors like futibatinib and pemigatinib. 2

Countermeasures for Side Effects

Gastrointestinal Side Effects

Managing gastrointestinal side effects may involve adjusting medication dosage, switching to a different FGFR inhibitor, or using medications to alleviate symptoms. 2

Comparison Between Studies

Commonalities Between Studies

All three studies highlight the potential of FGFR inhibitors in treating various cancers, particularly those with FGFR2 gene mutations. They also emphasize the need for further research to address resistance mechanisms and side effect profiles associated with these drugs. 3 , 2

Differences Between Studies

The studies differ in their focus: 1 focuses on the use of folic acid and folinic acid in rheumatoid arthritis treatment, 2 examines the efficacy of infigratinib in cholangiocarcinoma, and 3 provides a broader overview of FGFR inhibitors in oncology. 3 , 2

Points to Note Regarding Application to Real Life

While FGFR inhibitors are promising treatments, they carry the risk of side effects. Patients should consult with their healthcare providers to discuss the benefits and risks before making a decision about treatment. 3 , 2

Limitations of Current Research

Further research is needed to address the limitations of FGFR inhibitors, including understanding the mechanisms of resistance and improving the management of side effects. 3

Future Research Directions

Future research should focus on developing new FGFR inhibitors with fewer side effects, exploring combination therapies with existing drugs, and finding ways to overcome resistance to FGFR inhibitors. 3

Conclusion

FGFR inhibitors have emerged as targeted therapies for specific cancers, but further research is necessary to optimize their effectiveness and minimize side effects. Patients should discuss their treatment options and potential side effects with their healthcare providers to make informed decisions. 3 , 2