Oxaliplatin

證據等級: L5

預測適應症: 4 個

Oxaliplatin: From Colorectal Cancer to Malignant Pleural Mesothelioma

One-Sentence Summary

Oxaliplatin is a third-generation platinum-based chemotherapy agent, internationally established as part of the FOLFOX regimen for metastatic colorectal cancer. The TxGNN model predicts it may also be effective for Malignant Pleural Mesothelioma, with 6 clinical trials and 20 publications currently supporting this direction, including a completed Phase II trial directly testing oxaliplatin in this population.

Quick Overview

Item	Content
Original Indication	Not on file in this evidence pack (no license record); internationally recognized for metastatic colorectal cancer (FOLFOX regimen)
Predicted New Indication	Malignant Pleural Mesothelioma
TxGNN Prediction Score	99.68%
Evidence Level	L2
US Market Status	Not Marketed
Number of NDAs	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Detailed formal mechanism-of-action data from DrugBank is currently a flagged data gap (DG002). Based on known pharmacology, oxaliplatin is a third-generation platinum compound that forms DNA-platinum adducts and interstrand cross-links, blocking DNA replication and transcription and inducing apoptosis in rapidly dividing cells — the same mechanistic class as cisplatin, which along with pemetrexed forms the current standard-of-care backbone for malignant pleural mesothelioma (MPM).

Oxaliplatin’s original clinical use in colorectal cancer relies on this same DNA cross-linking cytotoxicity. Because MPM is also treated with platinum-based combination chemotherapy as its backbone, there is strong mechanistic overlap between the two indications: both are solid tumors relying on DNA-damage-induced apoptosis for treatment response.

This mechanistic rationale is further reinforced by real-world clinical development history — multiple completed Phase II trials have already tested oxaliplatin in combination with gemcitabine or raltitrexed specifically in MPM patients, providing direct (not merely theoretical) support for the TxGNN prediction.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00859469	Phase 2	Completed	29	Oxaliplatin + gemcitabine as first- or second-line therapy for pleural/peritoneal mesothelioma; directly evaluates response rate to this combination
NCT00996385	Phase 2	Unknown	29	Bortezomib (Velcade) + oxaliplatin (Eloxatin) in previously treated pleural/peritoneal mesothelioma
NCT03210298	N/A (registry)	Unknown	1000	Multicenter international PIPAC/PITAC registry documenting outcomes for peritoneal/pleural malignancies; not oxaliplatin-specific
NCT06310473	Phase 2	Not yet recruiting	30	Neoadjuvant chemoimmunotherapy for gastroesophageal junction/gastric cancer; relevance to MPM appears to be a keyword mismatch
NCT05107674	Phase 1	Recruiting	345	Dose-escalation study of CBL-B inhibitor NX-1607 in advanced malignancies; not an oxaliplatin trial
NCT07532902	Phase 1	Recruiting	60	Basket trial of BMS-986504 in MTAP-deleted solid tumors; not an oxaliplatin trial

Literature Evidence

PMID	Year	Type	Journal	Key Findings
12525529	2003	Phase 2 trial	J Clin Oncol	Raltitrexed + oxaliplatin combination shown active in diffuse malignant pleural mesothelioma (70 patients)
11989592	2001	Phase 2 trial	Tumori	Oxaliplatin + raltitrexed pilot study in inoperable MPM
14609447	2003	Phase 2 trial	Clin Lung Cancer	Multicenter Phase II of gemcitabine + oxaliplatin in MPM (n=25)
19091133	2008	Observational	J Occup Med Toxicol	Gemcitabine + oxaliplatin in pemetrexed-pretreated MPM patients
15639727	2005	Phase 2 trial	Lung Cancer	Vinorelbine + oxaliplatin as first-line therapy in MPM
15893013	2005	Phase 2 trial	Lung Cancer	Raltitrexed-oxaliplatin found inactive as second-line MPM therapy (negative result)
10930799	2000	Institutional review	Eur J Cancer	Institut Gustave Roussy 9-year experience with chemo/chemo-immunotherapy including raltitrexed-oxaliplatin in mesothelioma
15261443	2004	Review	Lung Cancer	Review of chemotherapy results and developments in MPM
11836672	2002	Review	Semin Oncol	Emerging role of antifolates, including the raltitrexed/oxaliplatin combination, in MPM
26526504	2015	Review	Cancer Treat Rev	Platinum + pemetrexed noted as standard of care in MPM; context for vinca alkaloid alternatives

US Market Information

This drug currently has no marketing license on file in this evidence pack (Market Status: Not Marketed; Total Licenses: 0).

Cytotoxicity

Item	Content
Cytotoxicity Classification	Conventional cytotoxic chemotherapy (platinum-based DNA cross-linking agent)
Myelosuppression Risk	Not specified in evidence pack — please refer to the package insert warnings and precautions
Emetogenicity Classification	Not specified in evidence pack — please refer to the package insert warnings and precautions
Monitoring Items	CBC with differential, renal function, and peripheral neuropathy assessment (standard for platinum-based agents)
Handling Protection	Requires cytotoxic drug handling precautions per standard chemotherapy handling protocols

Safety Considerations

Please refer to the package insert for safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Multiple completed Phase II trials (notably NCT00859469, and the published raltitrexed/gemcitabine-oxaliplatin combination studies) directly support the biological plausibility and clinical signal of oxaliplatin in malignant pleural mesothelioma, justifying an L2 evidence level. However, a Blocking-severity data gap exists at the drug level: TFDA-equivalent label warnings and contraindications (DG001) are unavailable, which prevents formal entry into the safety pre-assessment stage.

To proceed, the following is needed:

TFDA/regulatory label PDF with warnings and contraindications (DG001, Blocking)
Formal DrugBank mechanism-of-action data (DG002)
Confirmation of original approved indication and license status
Safety monitoring plan addressing known platinum-class risks (myelosuppression, peripheral neuropathy, renal function)
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.