Oxaliplatin
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Oxaliplatin: From Colorectal Cancer to Malignant Pleural Mesothelioma
One-Sentence Summary
Oxaliplatin is a third-generation platinum-based cytotoxic agent, internationally established as a backbone chemotherapy for colorectal cancer (commonly as part of the FOLFOX regimen). The TxGNN model predicts it may also be effective for Malignant Pleural Mesothelioma, with 5 clinical trials and 20 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not documented in this Evidence Pack; internationally established use is metastatic colorectal cancer (well-known standard use, not confirmed via Denmark registration data) |
| Predicted New Indication | Malignant Pleural Mesothelioma |
| TxGNN Prediction Score | 99.68% |
| Evidence Level | L2 |
| Denmark Market Status | Not marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data for this evaluation is not available in the Evidence Pack. Based on well-established pharmacological knowledge, oxaliplatin is a platinum-based DNA-crosslinking agent that induces apoptosis in rapidly dividing cells; it has proven efficacy in colorectal cancer, typically as part of combination regimens (e.g., FOLFOX).
Malignant pleural mesothelioma (MPM) is, like colorectal cancer, a solid tumour type where platinum-based cytotoxic chemotherapy (cisplatin/carboplatin plus pemetrexed) is already standard of care. Oxaliplatin’s DNA-damaging mechanism is not tumour-type specific, which provides a plausible mechanistic rationale for activity in MPM, a chemoresistant malignancy where treatment options remain limited.
This mechanistic plausibility is reinforced by a substantial and consistent body of independent literature: multiple prospective Phase II trials from different research groups (raltitrexed+oxaliplatin, gemcitabine+oxaliplatin, vinorelbine+oxaliplatin) have specifically tested oxaliplatin-based combinations in MPM populations since the early 2000s, indicating the oncology community has already explored this exact repurposing hypothesis clinically.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00859469 | Phase 2 | Completed | 29 | Oxaliplatin + gemcitabine as first- or second-line therapy in malignant pleural/peritoneal mesothelioma; evaluated response rate |
| NCT00996385 | Phase 2 | Unknown | 29 | Bortezomib (Velcade) plus oxaliplatin (Eloxatin) in previously treated pleural/peritoneal mesothelioma |
| NCT03210298 | N/A | Unknown | 1000 | Multicenter international registry documenting PIPAC/PITAC (pressurized intraperitoneal aerosol chemotherapy) outcomes for malignant pleural and peritoneal disease |
| NCT05107674 | Phase 1 | Recruiting | 345 | First-in-human dose-escalation study of CBL-B inhibitor NX-1607 in advanced malignancies (basket trial; not oxaliplatin-specific) |
| NCT06310473 | Phase 2 | Not yet recruiting | 30 | Neoadjuvant PD-1/CTLA-4 bispecific antibody plus chemotherapy in gastroesophageal junction/gastric cancer — disease match to MPM is weak, likely a knowledge-graph mapping artifact |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 14609447 | 2003 | Phase II trial | Clinical Lung Cancer | Multicenter Phase II study of gemcitabine + oxaliplatin in 25 MPM patients |
| 12525529 | 2003 | Phase II trial | J Clin Oncol | Raltitrexed + oxaliplatin combination shown to be an active regimen in 70 MPM patients |
| 15639727 | 2005 | Phase II trial | Lung Cancer | Vinorelbine + oxaliplatin as first-line therapy in untreated MPM |
| 11989592 | 2001 | Pilot study | Tumori | Oxaliplatin + raltitrexed in inoperable MPM; follow-up to earlier Phase I signal |
| 19091133 | 2008 | Observational study | J Occup Med Toxicol | Gemcitabine + oxaliplatin in pemetrexed-pretreated MPM patients |
| 15893013 | 2005 | Phase II trial | Lung Cancer | Raltitrexed-oxaliplatin as second-line therapy — reported inactive (no objective responses), important negative signal |
| 10930799 | 2000 | Retrospective review | Eur J Cancer | Institut Gustave Roussy 9-year experience with chemo/chemo-immunotherapy incl. raltitrexed-oxaliplatin in mesothelioma |
| 12610498 | 2003 | Review | Br J Cancer | Review of past and emerging chemotherapy results in MPM, including platinum-based regimens |
| 26526504 | 2015 | Review | Cancer Treatment Reviews | Review of chemotherapeutic options, including platinum combinations, in MPM management |
| 31455014 | 2019 | Review | Int J Mol Sci | Effect of chemotherapeutic agents, including oxaliplatin, on immune checkpoint expression in MPM — rationale for combination with immunotherapy |
Denmark Market Information
Currently no marketing authorisations for Oxaliplatin are recorded for Denmark in this Evidence Pack (total_licenses: 0).
Cytotoxicity
Oxaliplatin is a conventional cytotoxic chemotherapy agent (third-generation platinum compound), based on its known pharmacological class.
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (Platinum compound) |
| Myelosuppression Risk | Moderate — neutropenia and thrombocytopenia are recognised class effects of platinum agents; please refer to the SmPC for detailed grading |
| Emetogenicity Classification | Moderate to high — please refer to the SmPC and local antiemetic guidelines |
| Monitoring Items | CBC with differential, renal function, and clinical assessment for peripheral neuropathy (a characteristic dose-limiting toxicity of oxaliplatin) |
| Handling Protection | Standard cytotoxic drug handling and disposal precautions required |
Safety Considerations
Please refer to the approved Summary of Product Characteristics (SmPC) for safety information. No warnings, contraindications, or drug-interaction data were available in this Evidence Pack (labelled as Blocking data gap DG001: TFDA/SmPC warnings and contraindications not yet retrieved).
Conclusion and Next Steps
Decision: Hold
Rationale:
- Efficacy evidence for oxaliplatin in malignant pleural mesothelioma is moderate (L2) — multiple independent Phase II trials support activity, though results are mixed (e.g., PMID 15893013 reported an inactive second-line regimen) and no Phase 3 confirmation exists.
- A Blocking-severity data gap (DG001: missing SmPC warnings/contraindications) prevents any safety pre-assessment (S1), and the drug currently has no marketing authorisation in Denmark, so this candidate cannot proceed further until these gaps are closed.
To proceed, the following is needed:
- TFDA/SmPC warnings, contraindications, and full prescribing information (DG001, Blocking)
- Confirmed mechanism of action data (DG002, High priority)
- A defined regulatory pathway for Denmark market access, given the current “not marketed” status
- Resolution of disease-mapping ambiguity for lower-ranked candidates (e.g., “malignant visceral pleura tumor,” “female breast carcinoma”) where trial/literature relevance appears weak relative to the TxGNN score
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.