Pemetrexed
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
- Pemetrexed
- Pemetrexed: From Non-Small Cell Lung Cancer and Pleural Mesothelioma to Malignant Peritoneal Mesothelioma
Pemetrexed: From Non-Small Cell Lung Cancer and Pleural Mesothelioma to Malignant Peritoneal Mesothelioma
One-Sentence Summary
Pemetrexed is an antifolate chemotherapy originally used for non-small cell lung cancer and malignant pleural mesothelioma. The TxGNN model predicts it may be effective for malignant peritoneal mesothelioma, with 7 clinical trials and 20 publications currently supporting this direction. Pemetrexed-platinum is already used for this disease by extrapolation from pleural disease, so this is closer to a label extension than a novel repurposing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Non-small cell lung cancer; malignant pleural mesothelioma (the Singapore licence records contain no indication text, so this comes from the knowledge-graph indication data) |
| Predicted New Indication | Malignant peritoneal mesothelioma |
| TxGNN Prediction Score | 99.99% |
| Evidence Level | L2 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 13 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, pemetrexed is a multitargeted antifolate that inhibits thymidylate synthase, DHFR and GARFT. This disrupts folate-dependent nucleotide synthesis and slows tumour cell growth.
Its efficacy in malignant pleural mesothelioma is established. A Phase 3 RCT of pemetrexed plus cisplatin versus cisplatin alone showed a survival benefit and led to approval. Peritoneal mesothelioma shares the same histology and basic biology, so the mechanism is expected to carry over.
Peritoneal disease is typically treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) when the patient is suitable. For advanced disease, pemetrexed-platinum is already the commonly used systemic regimen. However, peritoneal-specific prospective evidence is scarce, and recommendations are mostly extrapolated from pleural trials.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT05001880 | Phase 2 | Recruiting | 66 | Randomized: carboplatin, pemetrexed and bevacizumab with or without atezolizumab in peritoneal mesothelioma |
| NCT03875144 | Phase 2 | Suspended | 66 | MESOTIP: PIPAC plus cisplatin-pemetrexed versus systemic chemotherapy alone as first-line therapy |
| NCT00061477 | Phase 2 | Completed | 48 | Pemetrexed plus gemcitabine front-line in pleural or peritoneal mesothelioma (combined population) |
| NCT06543069 | Phase 2 | Recruiting | 28 | Single-arm: sintilimab and bevacizumab with pemetrexed and cisplatin in unresectable peritoneal mesothelioma |
| NCT06057935 | Phase 2 | Recruiting | 64 | ICARuS II: intraperitoneal versus intravenous chemotherapy after cytoreductive surgery and HIPEC |
| NCT02535312 | Phase 1/2 | Active, not recruiting | 30 | TRC102 with cisplatin and pemetrexed in advanced solid tumours or mesothelioma (peritoneal is a subset) |
| NCT00402766 | Phase 1 | Completed | 19 | Cisplatin, pemetrexed and imatinib in metastatic malignant mesothelioma; mainly a dose-finding safety study |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31287877 | 2019 | Retrospective study | Jpn J Clin Oncol | Efficacy and safety of first-line pemetrexed plus cisplatin in advanced peritoneal mesothelioma |
| 28594258 | 2017 | Retrospective study | Expert Rev Anticancer Ther | First-line pemetrexed-cisplatin outcomes in peritoneal mesothelioma |
| 21528659 | 2011 | Single-institution study | Tumori | Pemetrexed-cisplatin in chemo-naïve peritoneal mesothelioma |
| 41133016 | 2025 | Retrospective comparison | Clin Med Insights Oncol | Pemetrexed-platinum versus gemcitabine-platinum as first-line therapy |
| 38806763 | 2024 | Multi-centre cohort | Ann Surg Oncol | Treatment strategies and outcomes in peritoneal mesothelioma |
| 39413826 | 2024 | Review | J Natl Compr Canc Netw | Systemic options are mostly extrapolated from pleural mesothelioma trials |
| 36765620 | 2023 | Review | Cancers | Diagnostic and therapeutic pathway; CRS plus HIPEC gives the best survival in selected patients |
| 35407498 | 2022 | Review | J Clin Med | Treatment of peritoneal mesothelioma; CRS plus HIPEC is the preferred initial treatment in selected patients |
| 30450291 | 2018 | Review | Transl Lung Cancer Res | Overview of this rare malignancy and its poor prognosis |
| 26941986 | 2016 | Review | J Gastrointest Oncol | Diagnosis and management of peritoneal mesothelioma |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN13480P | ALIMTA 100mg Powder for Solution for Infusion | Lyophilized powder for infusion | Indication text not recorded |
| SIN14536P | Pemetrexed Powder for Solution for Infusion 500mg/vial (Mylan) | Lyophilized powder for infusion | Indication text not recorded |
| SIN15466P | Pemcord 100 Powder for Solution for Infusion | Powder for infusion | Indication text not recorded |
| SIN15621P | PEMEX Powder for Solution for Injection 500mg/vial | Lyophilized powder for injection | Indication text not recorded |
| SIN16814P | PEMETREXED KABI Concentrate for Solution for Infusion 25mg/ml | Solution concentrate for infusion | Indication text not recorded |
There are 13 valid single-ingredient licences in total, all for injectable forms.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (antifolate class) |
| Myelosuppression Risk | Medium to high. The knowledge graph links pemetrexed with neutropenia, thrombocytopenia, anaemia and agranulocytosis. |
| Emetogenicity Classification | Low to moderate |
| Monitoring Items | Complete blood count with differential, renal function (including creatinine clearance), liver function |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Please refer to the package insert warnings and precautions for full details.
Safety Considerations
- Contraindication-related conditions (knowledge-graph associations, not label text): kidney disease and impaired renal function, thrombocytopenia, neutropenia, agranulocytosis, anaemia (including macrocytic anaemia), and pyoureter.
- Drug Interactions: 100 interactions were found. The main ones shown are all moderate: NSAID-type and salicylate drugs (acetylsalicylic acid, mesalazine, balsalazide, olsalazine), H2 blockers (famotidine, ranitidine, cimetidine), metformin, amphotericin B formulations, aminoglycosides and polymyxin B (kanamycin, neomycin, polymyxin B), vancomycin, amoxicillin, levofloxacin and sapropterin. Many of these affect renal clearance or kidney function.
Please refer to the package insert for label warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Pemetrexed-platinum has Phase 3 evidence in pleural mesothelioma and is already the standard systemic backbone for peritoneal mesothelioma by extrapolation. Peritoneal-specific evidence is limited to small Phase 2 trials and retrospective series, so the evidence level is L2.
To proceed, the following is needed:
- Package insert warnings and contraindications from HSA, which are currently missing and block formal safety screening
- Detailed mechanism of action data from DrugBank
- Confirmation of the approved indication text for the Singapore licences
- Results from the ongoing randomized peritoneal trials (NCT05001880, NCT03875144, NCT06057935)
- Renal function and blood count monitoring plan, with vitamin supplementation and interaction review (especially NSAIDs and nephrotoxic drugs)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.