Oxaliplatin
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Oxaliplatin: From Metastatic Colon Cancer to Malignant Pleural Mesothelioma
One-Sentence Summary
Oxaliplatin is a platinum-based chemotherapy drug, originally used to treat metastatic colon cancer. The TxGNN model predicts it may be effective for malignant pleural mesothelioma, with 2 directly relevant Phase 2 clinical trials and about 20 publications (mostly small Phase II studies and reviews) currently supporting this direction. No Phase 3 trial has shown it to be better than the standard regimen.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Metastasis from malignant tumour of colon (the Singapore licence records contain no approved indication text) |
| Predicted New Indication | Malignant pleural mesothelioma |
| TxGNN Prediction Score | 99.68% |
| Evidence Level | L2 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 12 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known information, oxaliplatin is a third-generation platinum agent that forms DNA adducts, which inhibits DNA synthesis and repair. Its efficacy in colorectal cancer is established, and mechanistically it may be applicable to mesothelioma.
Platinum-based chemotherapy (cisplatin or carboplatin) is already the established backbone of mesothelioma treatment. A platinum analogue with a different resistance profile is therefore biologically plausible. Phase II studies show activity when oxaliplatin is combined with gemcitabine, raltitrexed or vinorelbine.
The evidence has clear limits. No Phase 3 randomised trial shows oxaliplatin to be better than the standard cisplatin/pemetrexed regimen. One small second-line study of raltitrexed plus oxaliplatin (14 patients) found no objective responses.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00996385 | Phase 2 | Unknown | 29 | Bortezomib (Velcade) plus oxaliplatin in previously treated pleural or peritoneal mesothelioma; no results available |
| NCT00859469 | Phase 2 | Completed | 29 | Oxaliplatin plus gemcitabine as first- or second-line therapy in pleural or peritoneal mesothelioma; single-arm, response rate as the question |
| NCT07532902 | Phase 1 | Recruiting | 60 | BMS-986504 basket trial in MTAP-deleted solid tumours; oxaliplatin is only a background therapy, so low relevance |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 14609447 | 2003 | Phase II trial | Clin Lung Cancer | Multicentre study of gemcitabine plus oxaliplatin in 25 patients with mesothelioma |
| 12525529 | 2003 | Phase II trial | J Clin Oncol | Raltitrexed plus oxaliplatin in 70 patients (15 pretreated, 55 chemotherapy-naive); described as an active regimen |
| 15639727 | 2005 | Phase II trial | Lung Cancer | Vinorelbine plus oxaliplatin as first-line therapy in untreated mesothelioma |
| 11989592 | 2001 | Phase II pilot | Tumori | Oxaliplatin plus raltitrexed in inoperable pleural mesothelioma |
| 19091133 | 2008 | Observational / retrospective | J Occup Med Toxicol | Gemcitabine plus oxaliplatin in patients pretreated with pemetrexed |
| 15893013 | 2005 | Phase II trial | Lung Cancer | Raltitrexed plus oxaliplatin as second-line therapy was inactive: no objective responses in 14 patients, stable disease in 4 |
| 15261443 | 2004 | Review | Lung Cancer | Review of chemotherapy for pleural mesothelioma; response rates above 30% rarely achieved with established agents |
| 12610498 | 2003 | Review | Br J Cancer | Review of phase II-III chemotherapy studies in pleural mesothelioma |
| 11836672 | 2002 | Review | Semin Oncol | Antifolate-based regimens, including raltitrexed/oxaliplatin, in mesothelioma |
| 31455014 | 2019 | Preclinical / mechanistic | Int J Mol Sci | Effect of cisplatin, oxaliplatin and pemetrexed on immune checkpoint expression, relevant to combination with immunotherapy |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN13237P | Eloxatin 5mg/ml Concentrate for solution for infusion | Injection, solution, concentrate | Not available in the data |
| SIN14231P | Oxitan Injection 5mg/ml | Injection | Not available in the data |
| SIN14242P | Oliplat Injection 5 mg/ml | Injection, solution, concentrate | Not available in the data |
| SIN14481P | Oxaliplatin Sandoz Concentrate for Solution for Infusion 5mg/ml | Infusion, solution concentrate | Not available in the data |
| SIN16046P | Oxaccord Oxaliplatin Concentrate for Solution for Infusion USP 5 mg/ml | Infusion, solution concentrate | Not available in the data |
A further 7 valid licences are registered (12 in total), all single-ingredient injectable products.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (platinum class) |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Full blood count, liver and renal function; neurological assessment for peripheral neuropathy |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Disease associations flagged in the knowledge graph (not label text): kidney disease, liver disease, gallbladder disease, peripheral nervous system disease and peripheral neuropathy, and interstitial lung disease and pulmonary fibrosis.
- Drug Interactions: 100 interactions were recorded. One is classed Major: dolasetron. The rest listed are Moderate, including famotidine, amphotericin B, loperamide, mesalazine, balsalazide, bisacodyl, metronidazole, clarithromycin, vancomycin, kanamycin, levofloxacin, naltrexone, palonosetron and several laxatives or bowel-preparation agents.
Please also refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The evidence for mesothelioma consists of small Phase II studies, one of which found no responses, and no Phase 3 trial compares oxaliplatin with standard cisplatin/pemetrexed. Package-insert safety data are also missing, so a safety screen cannot yet be completed. The other predicted indications are weaker still. Epithelioid mesothelioma and female breast carcinoma have limited or indirect evidence, and the sarcomatoid, visceral pleura and rhabdomyosarcoma predictions rest almost entirely on the model.
To proceed, the following is needed:
- Package insert warnings and contraindications from the Singapore regulator (HSA)
- Detailed mechanism of action data
- Head-to-head or randomised evidence against the standard cisplatin/pemetrexed regimen
- Results from the completed and unknown-status Phase II trials (NCT00859469, NCT00996385)
- A review of the knowledge-graph disease associations (renal, hepatic, neuropathy, lung) against the label
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.