Oxaliplatin
| Evidence Level: L2 | Predicted Indications: 4 |
Table of Contents
Oxaliplatin: From Colorectal Cancer to Malignant Pleural Mesothelioma
One-Sentence Summary
Oxaliplatin is a third-generation platinum-based chemotherapy agent, historically used as a backbone of colorectal cancer regimens (e.g., FOLFOX). The TxGNN model predicts it may also be effective for Malignant Pleural Mesothelioma (MPM), with 5 relevant clinical trials and 20 literature records currently supporting this direction (top 10 of each shown below).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Colorectal cancer (part of platinum-based combination regimens such as FOLFOX) — no structured indication text is available in this evidence pack |
| Predicted New Indication | Malignant Pleural Mesothelioma |
| TxGNN Prediction Score | 99.68% |
| Evidence Level | L2 |
| India Market Status | Not Marketed |
| Number of Registrations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed structured mechanism-of-action (MOA) data is not available for this drug (flagged as a data gap, DG002). Based on the evidence pack’s repurposing rationale, Oxaliplatin is a third-generation platinum compound that forms DNA inter-/intra-strand crosslinks, inhibiting DNA replication and transcription and inducing apoptosis. This mechanism underlies its established efficacy in colorectal and other gastrointestinal cancers.
Malignant pleural mesothelioma tumor cells show moderate sensitivity to platinum agents. Clinically, platinum compounds (cisplatin/oxaliplatin) combined with antifolates (pemetrexed/raltitrexed) or gemcitabine are already used as first- or second-line chemotherapy backbones for MPM, and this combination approach has been validated in multiple prospective Phase 2 studies. This gives the TxGNN prediction a plausible mechanistic basis, though it should be noted the current standard-of-care platinum partner in MPM is cisplatin rather than oxaliplatin specifically — the evidence below is largely oxaliplatin-specific but still an alternative/second-line option rather than the established standard.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00859469 | Phase 2 | Completed | 29 | Oxaliplatin + gemcitabine as first- or second-line chemotherapy for pleural/peritoneal mesothelioma; evaluated response rate |
| NCT00996385 | Phase 2 | Unknown | 29 | Bortezomib (Velcade) + oxaliplatin (Eloxatin) in previously treated pleural/peritoneal mesothelioma, two-stage design |
| NCT03210298 | N/A (registry) | Unknown | 1000 | International multicenter observational registry of Pressurized IntraPeritoneal/IntraThoracic Aerosol Chemotherapy (PIPAC/PITAC), which includes malignant pleural cases; not oxaliplatin-specific, no predefined inclusion criteria |
Two additional trials (NCT05107674 — a CBL-B inhibitor study, and NCT06310473 — a gastric/esophagogastric junction cancer trial) were returned by the search but judged unrelated to oxaliplatin’s mechanism or the mesothelioma indication and were excluded from this table.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 11989592 | 2001 | Phase 2 trial | Tumori | Oxaliplatin + raltitrexed pilot study showed activity in inoperable malignant pleural mesothelioma |
| 14609447 | 2003 | Phase 2 trial (multicenter) | Clinical Lung Cancer | Gemcitabine + oxaliplatin in 25 MPM patients; evaluated response activity of the combination |
| 12525529 | 2003 | Phase 2 trial | J Clin Oncol | Raltitrexed + oxaliplatin combination showed activity in diffuse malignant pleural mesothelioma (70 patients) |
| 19091133 | 2008 | Cohort/retrospective | J Occup Med Toxicol | Oxaliplatin ± gemcitabine in pemetrexed-pretreated MPM patients; observational efficacy/safety study |
| 12610498 | 2003 | Review | British Journal of Cancer | Summarizes Phase II-III chemotherapy trials in MPM, including platinum-antimetabolite combinations |
| 15261443 | 2004 | Review | Lung Cancer | Overview of MPM chemotherapy results, highlighting antimetabolite/platinum combinations |
| 26526504 | 2015 | Review | Cancer Treatment Reviews | Reviews vinca alkaloids in MPM, contextualizing platinum-based regimens as standard backbone |
| 31455014 | 2019 | Review | Int J Molecular Sciences | Cisplatin, oxaliplatin and pemetrexed evaluated for immunomodulatory effects to inform combination with checkpoint inhibitors in MPM |
| 11836672 | 2002 | Review | Seminars in Oncology | Discusses antifolate/platinum (raltitrexed-oxaliplatin) combinations emerging as active MPM regimens |
| 12601280 | 2003 | Review | Current Opinion in Oncology | Reviews MPM chemotherapy outcomes, noting platinum-antifolate combinations among more effective regimens |
India Market Information
No India market authorizations are recorded for this drug in the current regulatory dataset (market status: Not Marketed; total registrations: 0).
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (platinum-based agent) |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Please refer to the package insert warnings and precautions |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Drug Interactions: Interaction database query completed with 631 total records identified. Notable interactions include:
- Major: Dolasetron
- Moderate: Famotidine, Amphotericin B (including lipid complex), Loperamide, Mesalazine, Balsalazide, Bisacodyl, Metronidazole, Clarithromycin, Picosulfuric acid, Polyethylene glycol (3350 with electrolytes), Palonosetron, Sodium sulfate, Vancomycin, Kanamycin, Naltrexone, Levofloxacin, Lactitol, Lactulose
Key warnings and contraindications are not available in this evidence pack (flagged as a blocking data gap, DG001) — please refer to the package insert for this information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple completed/near-complete Phase 2 trials and a consistent body of literature support oxaliplatin-based combinations (with gemcitabine, raltitrexed, or bortezomib) in malignant pleural mesothelioma, corresponding to Evidence Level L2. However, none of these are large randomized Phase 3 trials, and platinum-antifolate/platinum-gemcitabine combinations remain second-line/investigational rather than standard of care for MPM.
To proceed, the following is needed:
- TFDA/regulatory label warnings and contraindications (currently a blocking data gap, DG001)
- Detailed mechanism-of-action documentation (DG002)
- Route-of-administration compatibility confirmation (currently marked “pending” in the evidence pack)
- A formal safety monitoring plan, since key warnings/contraindications are not yet available
Related Predicted Subtypes (Lower Priority, Not Yet Actionable)
The evidence pack also includes related mesothelioma subtype predictions with substantially weaker evidence, listed here for context only:
| Disease | TxGNN Score | Evidence Level | Decision |
|---|---|---|---|
| Malignant epithelioid mesothelioma | 99.49% | L3 | Research Question |
| Sarcomatoid mesothelioma | 99.44% | L4 | Hold |
| Malignant visceral pleura tumor | 99.26% | L5 | Hold |
These subtypes currently lack subtype-specific clinical trial support and rely on indirect extrapolation from general mesothelioma or HIPEC/PIPAC literature; they are not recommended for further action at this time.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.