Oxaliplatin
| Evidence Level: L2 | Predicted Indications: 4 |
Table of Contents
- Oxaliplatin
- Pharmacist Assessment Report
- Oxaliplatin: From Metastatic Colon Cancer to Malignant Pleural Mesothelioma
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Canada Market Information
- Cytotoxicity
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Oxaliplatin: From Metastatic Colon Cancer to Malignant Pleural Mesothelioma
One-Sentence Summary
Oxaliplatin is a platinum-based chemotherapy drug originally used for metastatic colon cancer. The TxGNN model predicts it may be effective for malignant pleural mesothelioma, with 3 clinical trials (2 directly relevant Phase 2 studies) and 20 publications currently supporting this direction. The evidence consists mainly of small, single-arm Phase 2 studies.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Metastasis from malignant tumour of colon (the Health Canada licence records contain no indication text) |
| Predicted New Indication | Malignant pleural mesothelioma |
| TxGNN Prediction Score | 0.9968 |
| Evidence Level | L2 |
| Canada Market Status | Marketed (marketed DINs: 5 of 5) |
| Number of DINs | 5 (marketed: 5) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on general knowledge, oxaliplatin is a third-generation platinum agent that forms DNA adducts. These adducts block DNA replication and transcription and lead to cancer cell death.
Platinum agents such as cisplatin and carboplatin are the backbone of standard mesothelioma chemotherapy, so a class-level rationale exists. Oxaliplatin has shown activity in Phase 2 settings when combined with gemcitabine, raltitrexed, vinorelbine and bortezomib.
However, no Phase 3 randomised trial shows that oxaliplatin is better than the standard platinum-pemetrexed regimen. Results are also mixed: one raltitrexed-oxaliplatin study in second-line patients reported no objective responses. The high TxGNN score is therefore a hypothesis-generating signal, not proof of benefit.
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; open-label, results not 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 with standard-of-care therapy in MTAP-deleted solid tumours; oxaliplatin is likely only background therapy (low relevance) |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 14609447 | 2003 | Phase II trial | Clin Lung Cancer | Gemcitabine plus oxaliplatin in 25 patients with malignant pleural mesothelioma |
| 12525529 | 2003 | Phase II trial | J Clin Oncol | Raltitrexed plus oxaliplatin described as an active regimen (70 patients, 15 pretreated) |
| 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 mesothelioma |
| 19091133 | 2008 | Observational / Phase II | J Occup Med Toxicol | Gemcitabine plus oxaliplatin in patients pretreated with pemetrexed |
| 15893013 | 2005 | Phase II trial | Lung Cancer | Raltitrexed-oxaliplatin as second-line therapy was inactive (14 patients, no objective responses); closed early |
| 12610498 | 2003 | Review | Br J Cancer | Chemotherapy for mesothelioma; response rates above 30% rarely reached with established drugs |
| 15261443 | 2004 | Review | Lung Cancer | Update of phase II-III chemotherapy data in mesothelioma |
| 31455014 | 2019 | Review / preclinical | Int J Mol Sci | Effect of oxaliplatin and other chemotherapy on immune checkpoint expression; relevant to chemo-immunotherapy combinations |
| 10936465 | 2000 | Review | Crit Rev Oncol Hematol | Overview of oxaliplatin clinical activity across tumour types |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02458403 | Oxaliplatin Injection, USP | Not specified | Not specified |
| 02444763 | Oxaliplatin | Not specified | Not specified |
| 02435071 | Oxaliplatin Injection | Not specified | Not specified |
| 02457423 | Oxaliplatin Injection, USP | Not specified | Not specified |
| 02436957 | Oxaliplatin Injection | Not specified | Not specified |
All five licences are valid single-ingredient 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 | Please refer to the package insert; typically a complete blood count, liver and renal function, and neurological assessment |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Disease-related cautions (knowledge graph, not label text): The knowledge graph links oxaliplatin to caution in kidney disease, liver disease, gallbladder disease, peripheral nervous system disease and peripheral neuropathy, and interstitial lung disease and pulmonary fibrosis. These links should be checked against the official label. Lung disease is particularly relevant for a pleural mesothelioma population.
- Drug Interactions: 100 interactions were identified. The only one rated Major is dolasetron, which matters because antiemetics are routinely used with chemotherapy. Moderate interactions include:
- Famotidine
- Amphotericin B
- Loperamide
- Mesalazine and balsalazide
- Metronidazole
- Clarithromycin
- Palonosetron
- Vancomycin
- Kanamycin
- Levofloxacin
- Naltrexone
- Several laxatives and bowel-preparation agents
Label warnings and contraindications from the Health Canada package insert are not yet available.
Conclusion and Next Steps
Decision: Hold
Rationale: Evidence is limited to small, single-arm Phase 2 studies (about 25 to 70 patients each) with mixed results. No Phase 3 trial shows an advantage over the standard platinum-pemetrexed regimen. The label safety review also could not be completed. The other predicted mesothelioma subtypes are weaker still: epithelioid is L3, and sarcomatoid and visceral pleura tumour are L4 with no direct trials.
To proceed, the following is needed:
- Health Canada package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- Comparative evidence, such as a randomised study against standard platinum-pemetrexed, or evidence for use after pemetrexed failure
- Results from the completed trial NCT00859469 and a status update on NCT00996385
- Review of the neuropathy, kidney, liver and interstitial lung disease cautions, and the dolasetron interaction, for the mesothelioma population
- Confirmation of the approved indication text and dosage forms for each Canadian DIN
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.