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 platinum-based chemotherapy agent established for metastatic and adjuvant colorectal cancer (typically as part of the FOLFOX regimen). The TxGNN model predicts it may also be effective for Malignant Pleural Mesothelioma (MPM), with 5 clinical trials and 20 publications currently identified in this evidence pack supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Colorectal cancer (metastatic/adjuvant chemotherapy) — not derived from Australian regulatory data (drug not currently marketed in Australia; see below) |
| Predicted New Indication | Malignant Pleural Mesothelioma |
| TxGNN Prediction Score | 99.68% |
| Evidence Level | L2 |
| Australia Market Status | Not marketed |
| Number of ARTG Entries | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed DrugBank mechanism-of-action data was not available in this evidence pack (data gap). Based on the repurposing analysis that is available, Oxaliplatin is a third-generation, DACH-platinum compound that forms DNA cross-links, blocking replication and transcription and inducing apoptosis — the same general platinum mechanism as cisplatin, which underpins the current standard first-line therapy for MPM (cisplatin/pemetrexed).
Oxaliplatin’s established indication is colorectal cancer. Although colorectal cancer and MPM are anatomically distinct, both are platinum-responsive solid tumours where DNA-adduct formation drives cytotoxic effect, and MPM standard-of-care already depends on a platinum backbone combined with an antifolate agent (pemetrexed or raltitrexed).
This mechanistic overlap is directly supported in the evidence pack by multiple completed or near-complete Phase 2 trials that substitute oxaliplatin into MPM combination regimens (with gemcitabine or raltitrexed) instead of cisplatin, which is consistent with the high TxGNN prediction score (99.68%, model rank 4,323 of the disease vocabulary).
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00859469 | Phase 2 | Completed | 29 | Oxaliplatin (Eloxatin) + Gemcitabine as first- or second-line chemotherapy for pleural/peritoneal mesothelioma; direct oxaliplatin-in-MPM evidence |
| NCT00996385 | Phase 2 | Unknown | 29 | Velcade (bortezomib) + Eloxatin (oxaliplatin) in previously treated pleural/peritoneal mesothelioma patients |
| NCT03210298 | N/A | Unknown | 1000 | International PIPAC/PITAC registry for malignant pleural/peritoneal disease; multi-drug, not oxaliplatin-specific (Relevance grade B) |
| NCT06310473 | Phase 2 | Not yet recruiting | 30 | Neoadjuvant cadonilimab + chemotherapy for gastroesophageal junction/gastric cancer; disease mismatch — not MPM (Relevance grade C) |
| NCT05107674 | Phase 1 | Recruiting | 345 | CBL-B inhibitor NX-1607 in advanced malignancies; no direct oxaliplatin link (Relevance grade C) |
No ANZCTR-registered trials were identified for this indication in the evidence pack.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 12525529 | 2003 | Cohort (Phase 2) | J Clin Oncol | Raltitrexed + oxaliplatin active in diffuse MPM (n=70, chemo-naïve and pretreated) |
| 14609447 | 2003 | Cohort (Phase 2) | Clin Lung Cancer | Multicenter Phase 2 of gemcitabine + oxaliplatin in MPM (n=25) |
| 11989592 | 2001 | Cohort (Pilot) | Tumori | Oxaliplatin + raltitrexed pilot study in inoperable MPM |
| 19091133 | 2008 | Cohort (Observational) | J Occup Med Toxicol | Gemcitabine + oxaliplatin in MPM patients pretreated with pemetrexed |
| 15639727 | 2005 | Phase 2 trial | Lung Cancer | Vinorelbine + oxaliplatin as first-line therapy in untreated MPM |
| 15893013 | 2005 | Phase 2 trial | Lung Cancer | Raltitrexed-oxaliplatin inactive as second-line MPM treatment (negative result) |
| 10930799 | 2000 | Cohort | Eur J Cancer | Institut Gustave Roussy 9-year experience with chemo/chemo-immunotherapy in mesothelioma |
| 26526504 | 2015 | Review | Cancer Treat Rev | Vinca alkaloids in the therapeutic management of MPM; platinum/pemetrexed noted as standard of care |
| 11836672 | 2002 | Review | Semin Oncol | Antifolates in MPM treatment, including the raltitrexed/oxaliplatin combination |
| 12601280 | 2003 | Review | Curr Opin Oncol | Overview of chemotherapy for MPM, including platinum-based combinations |
Australia Market Information
Oxaliplatin is currently not marketed in Australia according to this evidence pack (0 ARTG entries recorded, market status “not marketed”). No product listing, dosage form, or approved indication text is available to summarise.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic — platinum compound (third-generation, DACH-platinum) |
| Myelosuppression Risk | Moderate (neutropenia and thrombocytopenia reported for this drug class); the dose-limiting toxicity for oxaliplatin specifically is typically cumulative peripheral sensory neuropathy rather than myelosuppression — please refer to the Product Information (PI) for full details |
| Emetogenicity Classification | Moderate to high (typical of platinum-class agents) |
| Monitoring Items | FBC with differential, renal function (oxaliplatin clearance is renal-dependent), neurological assessment for peripheral neuropathy, LFTs |
| Handling Protection | Yes — must follow standard cytotoxic drug handling and PPE protocols |
Safety Considerations
Please refer to the TGA-approved Product Information (PI) for safety information. This evidence pack has a blocking data gap on TFDA/TGA-equivalent warnings and contraindications (DG001), and drug interaction data was not found — safety data must be sourced before proceeding to formal safety review.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Two completed/near-complete Phase 2 trials and several supporting cohort studies directly test oxaliplatin-based combinations in MPM patients, giving Evidence Level L2. However, all studies are small (n=25–70), the drug is not currently marketed in Australia, and safety/PI data is missing — so this cannot yet advance without guardrails.
To proceed, the following is needed:
- TGA-approved Product Information (warnings, contraindications) — currently a blocking data gap
- Detailed mechanism-of-action data from DrugBank
- Drug-drug interaction data (currently not found)
- Confirmation of ARTG registration pathway, given the drug is not presently marketed in Australia
- Larger confirmatory trials, given the small sample sizes of existing Phase 2 MPM studies
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.