Side Effects of leucovorin: A Synthesis of Findings from 24 Studies

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Original Abstract of the Article

Major Research Findings

Leucovorin (folinic acid) is a drug used to reduce the side effects of methotrexate (MTX). MTX is used to treat cancer and autoimmune diseases, but it can cause side effects such as nausea, vomiting, and diarrhea. Leucovorin is believed to reduce these side effects by inhibiting the uptake of MTX into cells. 6

Leucovorin not only reduces the side effects of MTX but also has the potential to enhance the effectiveness of MTX. 3

However, there are concerns that leucovorin may inhibit the anti-cancer effect of MTX, and there have been limited reports on its clinical usefulness. Therefore, some doctors hesitate to include leucovorin in standard MTX prophylactic regimens. 12

Reasons for Side Effects

Leucovorin is thought to reduce side effects by inhibiting the uptake of MTX into cells. 3

Common Side Effects

Nausea

A common side effect of leucovorin is nausea. 6

Vomiting

A common side effect of leucovorin is vomiting. 6

Diarrhea

A common side effect of leucovorin is diarrhea. 6

Rash

A common side effect of leucovorin is rash. 6

Anemia

A common side effect of leucovorin is anemia. 6

Measures to Address Side Effects

Nausea

To reduce nausea, it is recommended to take leucovorin with meals. 6

Vomiting

To reduce vomiting, it is recommended to take leucovorin with meals. 6

Diarrhea

To reduce diarrhea, it is recommended to take leucovorin with meals. 6

Rash

If a rash occurs, consult your doctor. 6

Anemia

If anemia occurs, consult your doctor. 6

Comparison between Studies

Commonalities

Many studies have shown that leucovorin can reduce the side effects of MTX. 12 6 3

Differences

The effectiveness of leucovorin against MTX may vary depending on the patient and the dosage of MTX. 12

Notes on Application to Real Life

While leucovorin has been shown to reduce the side effects of MTX, it is not effective for all patients. 12 Consult your doctor before using leucovorin. 12

Limitations of Current Research

There are limited reports on the clinical effectiveness of leucovorin. 12

Future Research Directions

The effects of leucovorin on MTX need to be investigated further. 12

Conclusion

Leucovorin may have the potential to reduce the side effects of MTX. 12 Consult your doctor before using leucovorin. 12

Literature analysis of 24 papers
Positive Content
14
Neutral Content
1
Negative Content
9
Article Type
1
1
2
3
19
3.

Patient-derived oral mucosa organoids as an in vitro model for methotrexate induced toxicity in pediatric acute lymphoblastic leukemia.

Author: DriehuisE, OosteromN, HeilS G, MullerI B, LinM, KoldersS, JansenG, de JongeR, PietersR, CleversH, van den Heuvel-EibrinkM M

Decreased mucositis
Reduced MTX toxicity

This study uses organoids, 3D structures that mimic human oral mucosa, to study the effects of methotrexate (MTX) and leucovorin (LV) on oral mucositis. They found that LV can reduce MTX-induced toxicity in these organoids, suggesting that pretreatment with LV might reduce mucositis in patients.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

Calcium Folate for Reducing the Side Effects of Low-dose Methotrexate in Rheumatoid Arthritis: A Case Report.

Author: LiuRenzhu, YanQingzi, HuYixiang, LiuXiang

Accelerated methotrexate excretion
Hemocytopenia
Renal impairment

This report describes a rheumatoid arthritis patient experiencing adverse reactions to chronic methotrexate therapy, including hemocytopenia and renal impairment. Calcium folate and other measures were used to accelerate methotrexate excretion and alleviate the adverse reactions.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

6.

Overview of Methotrexate Toxicity: A Comprehensive Literature Review.

Author: HamedKhalid M, DighririIbrahim M, BaomarAbdulrahman F, AlharthyBaidaa T, AlenaziFoza E, AlaliGadheer H, AlenazyRawan H, AlhumaidiNidaa T, AlhulayfiDania H, AlotaibiYasmen B, AlhumaidanSarah S, AlhaddadZahra A, HumadiAdhwa'a A, AlzahraniShahad A, AlobaidRahaf H

Cancer treatment
Ectopic pregnancy treatment
Rheumatoid arthritis treatment
Bone marrow suppression
Hematologic toxicity
Infections
Nephrotoxicity
Pulmonary toxicity

Methotrexate (MTX), a widely used drug for rheumatoid arthritis and other conditions, can cause significant toxicity. Managing MTX toxicity involves careful monitoring, dose adjustments, and the use of appropriate antidotes.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

9.

Induction Therapy With Cisplatin, 5-Fluorouracil, Leucovorin, and Paclitaxel in Patients With Head and Neck Cancer.

Author: DE SaCarlos Eduardo Coelho, DE Iracema Gomes CuberoDaniel, DA CostaRafael Everton Assuncao Ribeiro, DI PardoRenato, CruzFelipe Jose Silva Melo, DE Melo SetteCláudia Vaz, DA SilvaEliana Araujo, Del GiglioAuro

Severe toxicity

This study evaluated the toxicities and response rate of a modified TPF (docetaxel, cisplatin, and 5-fluorouracil) protocol in patients with locally advanced head and neck cancer. Induction therapy with cisplatin, 5-fluorouracil, leucovorin, and paclitaxel in head and neck cancer is not feasible because of severe toxicity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

11.

Early weight loss is an independent risk factor for shorter survival and increased side effects in patients with metastatic colorectal cancer undergoing first-line treatment within the randomized Phase III trial FIRE-3 (AIO KRK-0306).

Author: LiuLian, EricksonNicole Tonya, RicardIngrid, von WeikersthalLudwig Fischer, LerchMarkus M, DeckerThomas, KianiAlexander, KaiserFlorian, HeintgesTobias, KahlChristoph, KullmannFrank, ScheithauerWerner, LinkHartmut, HöffkesHeinz-Gert, MoehlerMarkus, GesenhuesAlena Britta, TheurichSebastian, MichlMarlies, ModestDominik P, AlgülHana, StintzingSebastian, HeinemannVolker, HolchJulian W

mCRC treatment
weight maintenance
early weight loss
mCRC prognosis

This study found that early weight loss (EWL) in patients with metastatic colorectal cancer (mCRC) was associated with worse overall survival and progression-free survival. EWL was also associated with a higher incidence of side effects, such as diarrhea, edema, fatigue, nausea, and vomiting. The study also found that EWL was significantly associated with patient age, with older patients being at higher risk of EWL. These findings suggest that early preventative measures targeted at weight maintenance should be evaluated, especially in elderly patients being at highest risk of EWL.

Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

12.

Role of folinic acid in methotrexate-based prophylaxis of graft-versus-host disease following hematopoietic stem cell transplantation.

Author: AlJohaniNaif I

MTX toxicity control

Folinic acid (FA) can mitigate methotrexate (MTX) toxicity, a major concern in graft-versus-host disease (GvHD) prophylaxis. However, the efficacy of FA in adult patients is unproven. Further research is needed to confirm its benefits, optimize its use, and develop personalized prophylaxis regimens.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

14.

Lower Extremity Non-Blanchable Purpura Secondary to Methotrexate Toxicity: A Case Report.

Author: MateenSara, PontiousJane

Methotrexate toxicity
Skin necrosis

This case report describes a 61-year-old patient who experienced severe foot and ankle blistering as a result of methotrexate toxicity. The case highlights the importance of a thorough history and physical examination for proper diagnosis and treatment of methotrexate-related adverse effects.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

16.

Successful management and recovery of a dog with immune-mediated thrombocytopenia following vincristine overdose.

Author: PoirierMaude, BlongApril E, WaltonRebecca A L

Vincristine overdose management

A case report describes the successful management of severe vincristine overdose in a dog using Tbo-filgrastim, folinic acid, and glutamic acid along with aggressive supportive care.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

17.

Meta-analysis examining overall survival in patients with pancreatic cancer treated with second-line 5-fluorouracil and oxaliplatin-based therapy after failing first-line gemcitabine-containing therapy: effect of performance status and comparison with other regimens.

Author: WainbergZev A, FeeneyKynan, LeeMyung Ah, MuñozAndrés, GraciánAntonio Cubillo, LonardiSara, RyooBaek-Yeol, HungAnnie, LinYong, BendellJohanna, HechtJ Randolph

Improved survival

This systematic review assessed the safety and efficacy of FOLFOX for metastatic pancreatic cancer following prior gemcitabine-based therapy. A Bayesian meta-analysis was conducted to evaluate overall survival (OS) and compare outcomes with nanoliposomal irinotecan combination therapy. The review focused on providing evidence-based recommendations for treating pancreatic cancer patients who have previously received gemcitabine-based regimens.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

18.

Low-Dose Methotrexate Toxicity Presenting as Pancytopenia.

Author: DhillonGundip S, ChauhanSukhjinder, JalalYema, GhobrialYoussef, AhmedBirjees

Pancytopenia treatment
Pancytopenia

This case report presents an 82-year-old woman with severe pancytopenia induced by low-dose methotrexate (MTX). The patient was treated with leucovorin rescue therapy and granulocyte colony-stimulating factor (G-CSF) therapy. This case highlights the importance of monitoring for potential side effects even with low-dose MTX treatment.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

19.

Monitoring Of High-Dose Methotrexate (Mtx)-Related Toxicity and Mtx Levels in Children with Acute Lymphoblastic Leukemia: A Pilot-Study in Indonesia.

Author: SariNur Melani, RakhmillaLulu E, BashariMuhammad Hasan, ZazuliZulfan, SuryawanNur, SusanahSusi, ReniartiLelani, RaspatiHarry, SupriyadiEddy, KaspersGertjan J L, IdjradinataPonpon

MTX toxicity

This study investigates blood methotrexate (MTX) levels at 24 and 48 hours after high-dose MTX infusion in relation to clinical toxicity in childhood acute lymphoblastic leukemia (ALL). It evaluates the feasibility of MTX level monitoring in limited-resource settings to prevent toxicity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

20.

Extracorporeal Treatment for Methotrexate Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup.

Author: GhannoumMarc, RobertsDarren M, GoldfarbDavid S, HeldrupJesper, AnseeuwKurt, GalvaoTais F, NolinThomas D, HoffmanRobert S, LavergneValery, MeyersPaul, GosselinSophie, BotnaruTudor, MardiniKarine, WoodDavid M,

Methotrexate toxicity treatment

Extracorporeal treatments are not recommended for patients with severe methotrexate toxicity receiving standard care. Glucarpidase is the preferred treatment for severe methotrexate toxicity. The quality of evidence for these recommendations is very low.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

21.

Evaluation of adverse effects of chemotherapy regimens of 5-fluoropyrimidines derivatives and their association with DPYD polymorphisms in colorectal cancer patients.

Author: NegarandehReza, SalehifarEbrahim, SaghafiFatemeh, JalaliHossein, JanbabaeiGhasem, AbdhaghighiMohammad Javad, NosratiAnahita

Drug toxicity

Genetic polymorphism in the genes encoding dihydropyrimidine dehydrogenase (DPD) enzyme, which metabolizes fluoropyrimidine derivatives like 5-FU and capecitabine, may lead to decreased enzyme activity and potential toxicity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

22.

Incidence and management of patients with methotrexate delayed elimination in the clinical practice: A Delphi study.

Author: GrosLuis, RoldánAlicia, Cabero-MartínezAlmudena, Domínguez-PinillaNerea, de la FuenteAdolfo, González-BarcaEva, TassoMaría, TorrentMontserrat, GallardoEva, Del CerroInés, Giró-PerafitaAriadna, BadiaXavier

Acute kidney injury

High-dose methotrexate (HDMTX) is used to treat some cancers but can cause acute kidney injury (AKI) due to crystallization in renal tubules. This study aims to estimate the incidence and management of delayed MTX elimination and toxicity in Spain.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

23.

Leucovorin (folinic acid) rescue for high-dose methotrexate: A review.

Author: JiangRuiqi, MeiShenghui, ZhaoZhigang

Cancer treatment
Toxicity prevention
Leucovorin overrescue
Toxicity

This review discusses the use of high-dose methotrexate (HDMTX) for treating various cancers, focusing on managing its toxicities. It explores strategies like hydration, alkalization, leucovorin rescue, and haemodialysis to minimize side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

24.

Flat-dose versus weight or body surface area-based methotrexate dosing in low-risk gestational trophoblastic neoplasia.

Author: ParkerVictoria L, CushenBryony F, HillsAnnie, KandiahKaveetha, PalmerJulia E, SinghKamaljit, HancockBarry W, TidyJohn A, WinterMatthew C

LR-GTN treatment
Chemotherapy relapse

This study aims to determine the effect of methotrexate (MTX) dose adjustment by body surface area and weight upon chemotherapy response and disease relapse in LR-GTN patients.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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