Oxaliplatin
| Evidence Level: L2 | Predicted Indications: 4 |
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 3 clinical trials (2 directly relevant Phase 2 studies) and 20 publications currently supporting this direction. The evidence is limited to small, non-randomized Phase 2 studies.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Metastasis from malignant tumor of colon (from the knowledge graph; no approved indication text is available in the US license records) |
| Predicted New Indication | Malignant pleural mesothelioma |
| TxGNN Prediction Score | 99.68% |
| Evidence Level | L2 |
| US Market Status | Cancelled only (all 9 licenses cancelled) |
| Number of NDAs | 9 (all are ANDA generic applications) |
| Recommended Decision | Hold (research question) |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, oxaliplatin is a third-generation platinum compound that forms DNA crosslinks (adducts), which block DNA replication and trigger apoptosis. It has proven efficacy in colorectal cancer, particularly with 5-FU.
Platinum compounds such as cisplatin and carboplatin are already the backbone of mesothelioma chemotherapy, so activity through DNA damage is mechanistically plausible. Oxaliplatin has a different toxicity profile from cisplatin (less nephrotoxicity, but more neurotoxicity), so it could be an alternative where cisplatin is unsuitable. Phase 2 studies have tested it with gemcitabine, raltitrexed, vinorelbine and bortezomib. However, no Phase 3 randomized trial shows it is better than the standard cisplatin/pemetrexed regimen.
Two related predictions (epithelioid and sarcomatoid mesothelioma) and a visceral pleura tumor prediction are supported only by indirect evidence, so they are not the focus of this report.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00996385 | Phase 2 | Unknown | 29 | Bortezomib (Velcade) plus oxaliplatin (Eloxatin) in previously treated pleural or peritoneal mesothelioma; open-label, single-arm, up to 6 cycles; results not available |
| NCT00859469 | Phase 2 | Completed | 29 | Oxaliplatin plus gemcitabine as first- or second-line chemotherapy in pleural or peritoneal mesothelioma; primary question is response rate; non-randomized |
| NCT07532902 | Phase 1 | Recruiting | 60 | Basket trial of BMS-986504 with standard-of-care therapy in MTAP-deleted solid tumors; oxaliplatin is only part of the background regimen, so it is indirectly relevant |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 14609447 | 2003 | Phase II trial | Clin Lung Cancer | Multicenter study of gemcitabine plus oxaliplatin in 25 patients with malignant pleural 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 mesothelioma |
| 19091133 | 2008 | Observational study | J Occup Med Toxicol | Oxaliplatin with or without gemcitabine 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, and the trial was closed |
| 12610498 | 2003 | Review | Br J Cancer | Review of chemotherapy for malignant pleural mesothelioma; response rates above 30% rarely achieved with older cytotoxic drugs |
| 11836672 | 2002 | Review | Semin Oncol | Antifolate-based regimens, including raltitrexed/oxaliplatin, in mesothelioma |
| 10930799 | 2000 | Review of trials | Eur J Cancer | Institut Gustave Roussy experience in 163 mesothelioma patients, including raltitrexed-oxaliplatin |
| 31455014 | 2019 | Review/preclinical | Int J Mol Sci | Effect of cisplatin, oxaliplatin and pemetrexed on immune checkpoint expression in mesothelioma; supports combination with immunotherapy |
US Market Information
All 9 US licenses are ANDA generic applications, and all are cancelled. Approved indication text is not available in the license records.
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| ANDA207325 | Oxaliplatin | Injection, solution | Gland Pharma Limited |
| ANDA078817 | Oxaliplatin | Injection, solution | Sandoz Inc |
| ANDA204368 | Oxaliplatin | Injection, solution | BluePoint Laboratories |
| ANDA091358 | Oxaliplatin | Injection, solution | Mylan Institutional LLC |
| ANDA217348 | Oxaliplatin | Injection, solution | Meitheal Pharmaceuticals Inc. |
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 | CBC with differential, liver and renal function; neurological assessment for peripheral neuropathy |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Disease-related cautions (from the knowledge graph, not label text): kidney disease, liver disease, gallbladder disease, peripheral nervous system disease and peripheral neuropathy, interstitial lung disease, and pulmonary fibrosis. Peripheral neuropathy is consistent with the known neurotoxicity noted above.
- Drug Interactions: 100 interactions were identified. Among the listed examples, dolasetron is rated Major. Moderate interactions include famotidine, amphotericin B, loperamide, mesalazine, balsalazide, bisacodyl, metronidazole, clarithromycin, vancomycin, kanamycin, levofloxacin, palonosetron, naltrexone, and several laxatives or bowel-preparation agents (lactulose, lactitol, sodium sulfate, polyethylene glycol, picosulfuric acid).
Please refer to the package insert for official warnings and contraindications.
Conclusion and Next Steps
Decision: Hold (research question)
Rationale: Several Phase 2 studies show oxaliplatin-based combinations have some activity in pleural mesothelioma, but they are small and non-randomized. One second-line study found no objective responses. No Phase 3 trial shows an advantage over standard cisplatin/pemetrexed. Also, all US oxaliplatin licenses are cancelled, which complicates any near-term development path.
To proceed, the following is needed:
- Package insert warnings and contraindications, which are currently missing and block safety screening
- Detailed mechanism of action data
- Results from the completed Phase 2 trial (NCT00859469) and a comparison against cisplatin/pemetrexed, ideally in a randomized trial
- Clarification of current US regulatory status and the availability of marketed oxaliplatin products
- Subtype-specific data (epithelioid vs. sarcomatoid) before pursuing the related predictions
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.