Major Research Findings

Melphalan is a chemotherapy drug used to treat various cancers, particularly multiple myeloma. 1 It has been shown to be effective in reducing tumor mass and extending remission duration in patients with multiple myeloma. 1 However, melphalan is associated with several adverse effects, including mucositis, diarrhea, and myelosuppression. 18 The severity of these side effects can vary among individuals, and research has been conducted to understand the factors contributing to this variability.

One study found a significant correlation between creatinine levels and melphalan clearance, suggesting that kidney function might influence drug elimination. 18 Additionally, the study revealed a strong association between higher melphalan doses and increased risk of developing mucositis and diarrhea. 18 While genetic variations in glutathione S-transferase (GST) enzymes were initially investigated, further confirmation is needed to establish their definitive role in predicting side effects. 18

Research has also explored the impact of melphalan on oral mucosal microcirculation in myeloma patients undergoing high-dose chemotherapy followed by stem cell transplantation. 15 These studies have highlighted the potential negative effects of melphalan on blood vessel structure and function, contributing to the development of oral mucositis.

Preclinical studies suggest that combining melphalan with exportin 1 inhibitors (XPO1i) such as selinexor, eltanexor, and KOS-2464 might enhance the antitumor efficacy. 4 This combination has shown potential for treating both melphalan-resistant and newly diagnosed multiple myeloma, with a synergistic effect in killing cancer cells. 4 The synergistic effect is believed to stem from the combined inhibition of DNA repair mechanisms by melphalan and XPO1i. 4

The effects of melphalan on reproductive health have also been investigated. A study in rats showed that melphalan treatment induced germ cell toxicity, leading to decreased sperm count, motility, and morphological abnormalities. 3 However, the administration of β-aminoisobutyric acid (BAIBA) at high doses was found to mitigate these toxic effects by exhibiting antioxidant, anti-inflammatory, and anti-apoptotic properties. 3 This finding highlights the potential therapeutic benefit of BAIBA in protecting male reproductive health during melphalan-based chemotherapy.

Melphalan has been shown to have a detrimental effect on retinal pigment epithelial (RPE) cells in a cell culture model. 13 This observation aligns with clinical reports of RPE alterations following intra-arterial and intravitreal chemotherapy for retinoblastoma. 13 The findings suggest that melphalan treatment might impact vision, particularly in the context of eye cancer treatments.

Benefits and Risks

Benefits Summary

Melphalan is an effective chemotherapy drug for treating various cancers, particularly multiple myeloma. 1 It is often used in combination with other drugs to enhance its antitumor effects. 16 19 Recent research suggests that melphalan may also have immunostimulatory effects, potentially boosting the body's immune response to fight cancer. 11

Risks Summary

Melphalan can cause serious side effects, including mucositis, diarrhea, and bone marrow suppression. 18 The dose of melphalan is a crucial factor in determining the risk of developing these side effects. 18 Melphalan has also been linked to potential vision issues due to its effects on retinal pigment epithelial cells. 13

Comparison Across Studies

Commonalities

Multiple studies consistently highlight the effectiveness of melphalan in treating various cancers, particularly multiple myeloma. 1 16 19 Furthermore, several studies emphasize the potential for enhancing its therapeutic effects by combining it with other drugs. 4

Differences

There is variability in the reported side effects of melphalan across different studies. Some studies indicate a higher risk of severe side effects such as mucositis, diarrhea, and myelosuppression. 18 Other studies suggest that the adverse effects might be less severe. 11 These discrepancies could be attributed to factors such as the patient population, melphalan dose, and specific treatment protocols.

Consistency and Contradictions in Findings

The findings regarding the effectiveness of melphalan in treating cancers, particularly multiple myeloma, are consistent across different studies. 1 16 19 However, there are contradictions in the reported side effects. 18 11 Further investigation is needed to resolve these inconsistencies and better understand the factors that influence the risk and severity of side effects associated with melphalan therapy.

Considerations for Applying Findings in Real Life

While melphalan is an effective chemotherapy drug, it's important to be aware of its potential side effects. 18 The decision to use melphalan should be made on a case-by-case basis, considering the potential benefits and risks for each individual patient. 18 Close monitoring and careful management strategies are crucial for minimizing adverse events during melphalan therapy.

Limitations of Current Research

The research on melphalan side effects is still ongoing, and there are limitations to our current understanding. More studies are needed to fully comprehend the factors influencing the variability in side effects and develop strategies to mitigate these risks. 18

Future Research Directions

Future research should focus on identifying and developing methods to minimize the side effects of melphalan while maintaining its therapeutic effectiveness. 18 This could involve exploring alternative drug formulations, personalized dosing strategies based on individual patient factors, and potential combination therapies with other agents that mitigate side effects. 18

Conclusion

Melphalan is a valuable chemotherapy drug for treating various cancers, particularly multiple myeloma. 1 However, it is associated with several side effects. 18 Therefore, its use should be carefully considered on a case-by-case basis, and careful monitoring is essential to manage potential adverse events. 18 Further research is needed to fully understand the factors influencing side effects and develop strategies to improve patient safety and outcomes during melphalan therapy. 18