Reported positive (1)
- Application of anti-methotrexate Fab fragments for the optimization of intraperitoneal methotrexate therapy in a murine model of peritoneal cancer
Animal study · Preclinical only · Sep 2005
Methotrexate
Evidence at a glanceHuman trial / meta-analysisMixed results⚠ Studies disagree
2 published studies tagged to this agent1 human studies approved & graded (trial, observational, or meta-analysis)
Why this grade?
Human trial / meta-analysis — Includes human trial or meta-analysis evidence.
- 1 human · 1 animal · 0 lab · 0 review/other
- Most authoritative study: Phase 3 randomized trial of high-dose methotrexate for young children with high-risk embryonal brain tumors: A report from the Children's Oncology Group
- Studies disagree on the reported direction (conflict flagged).
- Findings conflict across studies
Computed deterministically from the studies’ types and reported outcomes — not written by AI, and not a claim that anything works.
Auto-discovered · not yet curatedmethotrexate
Educational only, not medical advice. OncoForge makes no claim that Methotrexate treats, prevents, or cures any condition, beyond what the linked studies show. Evidence levels vary; effects may not translate to people, and some compounds can cause harm. Always coordinate with your oncology team.
Simple Summary
Auto-discovered from 1 recent study; not yet curated.
Research
Where the evidence is
What has been studied, and how strong it is, by topic. A dashed cell means no studies were found for that combination — a gap, not evidence of no effect. Open a row to see its studies.
CancerHuman evidenceMechanismSafetyTrial
Embryonal Brain Tumors1——1
Embryonal Tumor With Multilayered Rosettes1——1
Group 3 Medulloblastoma1——1
Medulloblastoma1——1
Pineoblastoma1——1
Shh Medulloblastoma1——1
Peritoneal Sarcoma (Sarcoma 180)—1——
Reported figures
What supports this page
The kinds of sources behind this page, strongest at the top. Faint rungs show what is not here yet.
Guideline0
Meta-analysis0
Systematic review0
Randomized trial0
Clinical trial1
Observational0
Case report0
Review0
Preclinical1
Other0
2 studies1 human1 animal
Tracking 2 published studies of Methotrexate: 1 in humans, 1 in animals.
Reported direction across studies: 1 positive, 1 mixed.
Findings conflict — both supportive and negative/mixed results exist (see below). Human evidence is limited.
These counts summarize what the studies reported; they are not a measure of whether Methotrexate works.
Cancers named in these studies
embryonal brain tumors (1)medulloblastoma (1)Group 3 medulloblastoma (1)SHH medulloblastoma (1)embryonal tumor with multilayered rosettes (1)pineoblastoma (1)peritoneal sarcoma (Sarcoma 180) (1)
Conflicting evidence
Negative or mixed (1)
- Phase 3 randomized trial of high-dose methotrexate for young children with high-risk embryonal brain tumors: A report from the Children's Oncology Group
Human trial · Moderate evidence · Oct 2025
All studies
Human trialTrialMixed resultsModerate evidenceTier 4 · clinicaln = 77
Phase 3 randomized trial of high-dose methotrexate for young children with high-risk embryonal brain tumors: A report from the Children's Oncology Group
Neuro-oncology · Oct 2025 · phase 3 randomized controlled trial
Methotrexateembryonal brain tumorsmedulloblastomaGroup 3 medulloblastomaSHH medulloblastomaembryonal tumor with multilayered rosettespineoblastoma
This phase 3 randomized trial tested adding high-dose methotrexate to induction chemotherapy in children ≤36 months with high-risk embryonal brain tumors. Overall complete response rates were similar between arms, but in medulloblastoma patients methotrexate was associated with higher CR (63% vs 30%) and improved 5-year event-free survival in Group 3 medulloblastoma (70% vs 33.3%). No benefit was seen for embryonal tumor with multilayered rosettes or pineoblastoma.
Reported effects: eligible patients 77, n=77 · patients evaluated for response 59, n=59 · +8 more
Studied with: induction chemotherapy, high-dose consolidation chemotherapy with hematopoietic stem-cell infusion.
Key findings
- Of 77 eligible patients, 59 with detectable disease were evaluated for response and 28 (47.5%) achieved CR; 15/30 (50%) treated with methotrexate compared to 13/29 (45%) without methotrexate (P = 0.35).
- For medulloblastoma (MB), CR was 12/19 (63%) with methotrexate compared to 6/20 (30%) without methotrexate (P = 0.039).
- All SHH subtype MB (n = 11) were survivors (molecular characterization retrospective).
- Five-year event-free survival (EFS) for Group 3 MB was 70% (90% CI: 39.6-87.2) with methotrexate versus 33.3% (90% CI: 15.0-52.9) without (P = 0.037).
- In other embryonal tumors, CR was 3/11 (27%) with methotrexate compared to 7/9 (78%) without (P = 0.99).
- No benefit observed for Embryonal Tumor with Multilayered Rosettes (n = 14; EFS 20.0% [90% CI: 1.8-52.5] with methotrexate versus 33.3% [90% CI: 10.8-58.1] without, P = 0.58) or pineoblastoma (n = 9; EFS 16.7% [90% CI: 1.6-46.1] with methotrexate versus 0% without, P = 0.52).
Limitations: Relatively small overall sample size (77 eligible) with smaller numbers in histologic/molecular subgroups; Molecular characterization was conducted retrospectively; Some subgroup analyses involve very small n (e.g., Group 3 MB: 10 vs 15; SHH MB n=11); Tests of significance were one-sided (as stated); Confidence intervals reported are 90% rather than the more conventional 95%.
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Animal studyReported positivePreclinical onlyTier 2 · animal
Application of anti-methotrexate Fab fragments for the optimization of intraperitoneal methotrexate therapy in a murine model of peritoneal cancer
Journal of pharmaceutical sciences · Sep 2005 · preclinical comparative study in mice (dose and survival comparisons)
Methotrexateperitoneal sarcoma (Sarcoma 180)
In a mouse peritoneal cancer model, investigators produced anti-methotrexate Fab fragments (AMF), measured their pharmacokinetics, and tested whether systemic AMF could permit higher intraperitoneal methotrexate (MTX) doses and improve survival. AMF had a mean terminal half-life of 10.9 +/- 3.3 h and 28% +/- 7% s.c. bioavailability (at 2.2 g/kg). Co-administration of s.c. AMF (4.2 g/kg) increased the maximally tolerated i.p. MTX dose from 1.9 mg/kg to 10 mg/kg and increased median survival in some combination groups (e.g., to 17 and 14 days for MTX 7.5 or 10 mg/kg plus AMF).
Reported effects: mean terminal half-life of AMF 10.9 · s.c. bioavailability at 2.2 g/kg 28% · +7 more
Studied with: methotrexate.
Key findings
- The mean terminal half-life of AMF was found to be 10.9 +/- 3.3 h and was not dose-dependent, and s.c. bioavailability was 28% +/- 7% at 2.2 g/kg.
- In mice bearing peritoneal tumors, the maximally tolerated dose of i.p. MTX increased from 1.9 mg/kg (following i.p. MTX alone) to 10 mg/kg (with co-administration of s.c. AMF).
- Median survival times for saline-treated control animals and animals receiving i.p. MTX (1.9, 2.8, 3.8 mg/kg) were 9, 12, 10, and 7 days, respectively.
- For animals receiving combination therapy with i.p. MTX 7.5 or 10 mg/kg and 4.2 g/kg s.c. AMF, median survival time increased to 17 and 14 days, respectively.
Limitations: Animal (murine) study only — results may not translate to humans.; Single tumor model (Sarcoma 180) tested.; Sample sizes per group are not reported in the abstract.; No detailed toxicity or long-term outcome data reported in the abstract..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed
What changed recently
The latest additions to Methotrexate's evidence base, and anything that's been retracted.
Recently added- Phase 3 randomized trial of high-dose methotrexate for young children with high-risk embryonal brain tumors: A report from the Children's Oncology Group Human trial · added Jun 2026
- Application of anti-methotrexate Fab fragments for the optimization of intraperitoneal methotrexate therapy in a murine model of peritoneal cancer Animal study · added Jun 2026
Cancers where Methotrexate reported positive results
Where at least one study reported a positive result, shown with the full picture, not just the wins. Positive results are more likely to be published, and most of these are early lab or animal studies that may not translate to people. This reports what studies found, not what works.
Preclinical only: lab / animal (1)
Limitations: Animal (murine) study only — results may not translate to humans.; Single tumor model (Sarcoma 180) tested.; Sample sizes per group are not reported in the abstract.; No detailed toxicity or long-term outcome data reported in the abstract..
Cited positive studies (1)
Evidence at a glance: Methotrexate by cancer
A deterministic grade of what published studies report for each: strength of evidence, the reported direction, and the largest credible effect, strongest-evidence first. This summarizes findings; it is not a claim that anything works.
Embryonal brain tumorsHuman trial / meta-analysisMixed results1 human
Includes human trial or meta-analysis evidence.
Largest credible effect: 5-year EFS for Group 3 MB with methotrexate vs without 70% [39.6–87.2], p=0.037, n=25 PMID 40485042 · response rates 16.7–70 across 7 studies
Most authoritative study: Phase 3 randomized trial of high-dose methotrexate for young children with high-risk embryonal brain tumors: A report from the Children's Oncology Group
Based on a single study.
Embryonal tumor with multilayered rosettesHuman trial / meta-analysisMixed results1 human
Includes human trial or meta-analysis evidence.
Largest credible effect: 5-year EFS for Group 3 MB with methotrexate vs without 70% [39.6–87.2], p=0.037, n=25 PMID 40485042 · response rates 16.7–70 across 7 studies
Most authoritative study: Phase 3 randomized trial of high-dose methotrexate for young children with high-risk embryonal brain tumors: A report from the Children's Oncology Group
Based on a single study.
Group 3 medulloblastomaHuman trial / meta-analysisMixed results1 human
Includes human trial or meta-analysis evidence.
Largest credible effect: 5-year EFS for Group 3 MB with methotrexate vs without 70% [39.6–87.2], p=0.037, n=25 PMID 40485042 · response rates 16.7–70 across 7 studies
Most authoritative study: Phase 3 randomized trial of high-dose methotrexate for young children with high-risk embryonal brain tumors: A report from the Children's Oncology Group
Based on a single study.
MedulloblastomaHuman trial / meta-analysisMixed results1 human
Includes human trial or meta-analysis evidence.
Largest credible effect: 5-year EFS for Group 3 MB with methotrexate vs without 70% [39.6–87.2], p=0.037, n=25 PMID 40485042 · response rates 16.7–70 across 7 studies
Most authoritative study: Phase 3 randomized trial of high-dose methotrexate for young children with high-risk embryonal brain tumors: A report from the Children's Oncology Group
Based on a single study.
Includes human trial or meta-analysis evidence.
Largest credible effect: 5-year EFS for Group 3 MB with methotrexate vs without 70% [39.6–87.2], p=0.037, n=25 PMID 40485042 · response rates 16.7–70 across 7 studies
Most authoritative study: Phase 3 randomized trial of high-dose methotrexate for young children with high-risk embryonal brain tumors: A report from the Children's Oncology Group
Based on a single study.
SHH medulloblastomaHuman trial / meta-analysisMixed results1 human
Includes human trial or meta-analysis evidence.
Largest credible effect: 5-year EFS for Group 3 MB with methotrexate vs without 70% [39.6–87.2], p=0.037, n=25 PMID 40485042 · response rates 16.7–70 across 7 studies
Most authoritative study: Phase 3 randomized trial of high-dose methotrexate for young children with high-risk embryonal brain tumors: A report from the Children's Oncology Group
Based on a single study.
Animal studies only — no human data.
Largest credible effect: mean terminal half-life of AMF 10.9 PMID 16052545 · median-survival values 7–17 across 6 studies
Most authoritative study: Application of anti-methotrexate Fab fragments for the optimization of intraperitoneal methotrexate therapy in a murine model of peritoneal cancer
No human studies yet · Based on a single study.
Dose: as studied, not a recommendation
These are doses as studied or reported, never a recommendation. The right amount of Methotrexate depends on you, your other medicines, and your situation; decide it with your oncology team and pharmacist, not from a web page.
Doses reported in studies- Phase 3 randomized trial of high-dose methotrexate for young children with high-risk embryonal brain tumors: A report from the Children's Oncology Group high-dose (not specified in abstract) · Human trial · Oct 2025
- Application of anti-methotrexate Fab fragments for the optimization of intraperitoneal methotrexate therapy in a murine model of peritoneal cancer MTX: i.p. 72 h infusion at 1.9, 2.8, 3.8 mg/kg; also i.p. 72 h infusion at 7.5 or 10 mg/kg in combination groups. AMF: i.v. bolus 0.4 g/kg; s.c. bolus 0.4, 0.8, 2.2 g/kg for PK; combination used 4.2 g/kg s.c. AMF. · Animal study · Sep 2005
Clinical trials studying Methotrexate
0 ongoing · 8 completed · tracked from ClinicalTrials.gov. Recruiting is not the same as proven, and completed is not the same as positive — read the results. Not a recommendation.
Completed
- Combination Chemotherapy in Treating Patients With Stage II Bladder Cancer
- Methotrexate and Glucocorticoids in Treating Patients With Newly Diagnosed Acute Graft-Versus-Host Disease After Donor Stem Cell Transplant
- Early Administration of ATG Followed by Cyclophosphamide, Busulfan and Fludarabine Before a Donor Stem Cell Transplant in Patients With Hematological CancerPrimary outcome measured: Achievement of > 90% (Full) Donor Chimerism in the T-cell Lineage as Measured by PCR at Day 30 Post-transplantation
- Donor Stem Cell Transplant in Treating Young Patients With Relapsed or Refractory Solid Tumors
- Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Metastatic or Unresectable Kidney Cancer
- Trial of Sunitinib and/or Nivolumab Plus Chemotherapy in Advanced Soft Tissue and Bone SarcomasNCT03277924Phase 1 / Phase 2Completed Sun Jun 30tests Methotrexatetests Nivolumabtests Cisplatintests Dacarbazinetests Ifosfamidetests Doxorubicin
- Open-label Leucovorin Pharmacokinetic Study in Patients Receiving High Dose Methotrexate With or Without VoraxazePrimary outcome measured: Pharmacokinetics (PK) of Leucovorin
- Neoadjuvant Chemotherapy With Methotrexate, Vinblastine, Adriamycin and Cisplatin (M-VAC) Plus Avastin in Patients With Urothelial CancerPrimary outcome measured: Percentage of Participants With Response Defined as the Absence of Residual Muscle Invasive Cancer in Resected Specimen
1 stopped (terminated / withdrawn / suspended)
Inclusion here is not an endorsement. OncoForge makes no claim beyond what the linked studies show. Discuss anything on this page with your oncology team before acting on it.