Oxaliplatin

Evidence Level: L2

Predicted Indications: 4

Oxaliplatin

Pharmacist Assessment Report

Oxaliplatin: From Metastatic Colon Cancer to Malignant Pleural Mesothelioma

One-Sentence Summary

Oxaliplatin is a platinum-based chemotherapy agent originally used for metastatic colon cancer. The TxGNN model predicts it may be effective for malignant pleural mesothelioma, with 2 directly relevant Phase 2 clinical trials and several Phase 2 publications supporting this direction. No Phase 3 trial has shown it to be better than the current standard of care.

Quick Overview

Item	Content
Original Indication	Metastasis from malignant tumour of colon (the ARTG record compiled for this report has no indication text)
Predicted New Indication	Malignant pleural mesothelioma
TxGNN Prediction Score	0.9968
Evidence Level	L2
Australia Market Status	Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data
Number of PBS Items	1 (valid: 1)
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism of action data are not available in the data compiled for this report. Oxaliplatin is a third-generation platinum agent. Published literature describes it as forming DNA adducts (intrastrand cross-links) that inhibit DNA replication and transcription. It has shown activity in colorectal cancer, particularly with 5-fluorouracil.

Platinum-based chemotherapy is the established backbone of mesothelioma treatment. It is therefore mechanistically plausible that oxaliplatin could be active in pleural mesothelioma. Several Phase 2 studies support this: combinations with gemcitabine, vinorelbine and raltitrexed all showed some activity.

There are important caveats. No Phase 3 RCT shows oxaliplatin to be superior to the cisplatin/pemetrexed standard. One small second-line study of raltitrexed plus oxaliplatin (14 patients) reported no objective responses.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrolment	Key Findings
NCT00996385	Phase 2	Unknown	29	Bortezomib (Velcade) plus oxaliplatin in previously treated malignant pleural or peritoneal mesothelioma; up to 6 cycles, tumour response assessed by CT
NCT00859469	Phase 2	Completed	29	Oxaliplatin plus gemcitabine as first- or second-line therapy in pleural or peritoneal mesothelioma; primary question was response rate
NCT07532902	Phase 1	Recruiting	60	BMS-986504 basket trial with standard-of-care therapy in MTAP-deleted solid tumours; oxaliplatin is only a possible background agent (indirect relevance)

No Australian (ANZCTR) trial identifiers were found in the data compiled for this report.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
14609447	2003	Phase 2 trial	Clin Lung Cancer	Multicentre study of gemcitabine plus oxaliplatin in 25 patients with malignant pleural mesothelioma
15639727	2005	Phase 2 trial	Lung Cancer	Vinorelbine plus oxaliplatin as first-line therapy in untreated malignant pleural mesothelioma
12525529	2003	Phase 2 trial	J Clin Oncol	Raltitrexed plus oxaliplatin described as an active regimen in malignant mesothelioma (70 patients, pretreated and chemotherapy-naive)
11989592	2001	Pilot study	Tumori	Raltitrexed plus oxaliplatin in inoperable malignant pleural mesothelioma
19091133	2008	Observational / Phase 2	J Occup Med Toxicol	Oxaliplatin with or without gemcitabine in patients pretreated with pemetrexed
15893013	2005	Phase 2 trial	Lung Cancer	Raltitrexed plus oxaliplatin as second-line therapy was inactive: no objective responses in 14 patients
15261443	2004	Review	Lung Cancer	Review of chemotherapy for malignant pleural mesothelioma, with newer combinations appearing more promising
12610498	2003	Review	Br J Cancer	Review of Phase II-III chemotherapy studies in malignant pleural mesothelioma
31455014	2019	Review	Int J Mol Sci	Effect of cisplatin, oxaliplatin and pemetrexed on immune checkpoint expression in mesothelioma
10936465	2000	Review	Crit Rev Oncol Hematol	Overview of oxaliplatin clinical activity across tumour types

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 4542C	Oxaliplatin SUN	Solution concentrate for I.V. infusion, 200 mg in 40 mL	Not available in the compiled data

Cytotoxicity

Item	Content
Cytotoxicity Classification	Conventional cytotoxic (platinum class)
Myelosuppression Risk	Please refer to the Product Information (PI) warnings and precautions
Emetogenicity Classification	Please refer to the Product Information (PI) warnings and precautions
Monitoring Items	Full blood count, liver and renal function, and neurological assessment (peripheral neuropathy), per the PI
Handling Protection	Must follow cytotoxic drug handling regulations

Safety Considerations

Contraindication-related conditions (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 identified in total. Of the 20 listed in the compiled data, one is rated Major: dolasetron. The remainder are Moderate, including famotidine, amphotericin B, loperamide, mesalazine, balsalazide, bisacodyl, metronidazole, clarithromycin, palonosetron, vancomycin, kanamycin, naltrexone, levofloxacin, lactulose, lactitol, picosulfuric acid, sodium sulfate and polyethylene glycol with electrolytes.

Label-based warnings and contraindications were not available. Please refer to the TGA-approved Product Information (PI) for full safety information.

Conclusion and Next Steps

Decision: Hold

Rationale: Evidence for pleural mesothelioma is limited to small, mostly older Phase 2 studies (about 25 to 70 patients each), with mixed results, including one inactive second-line study. No Phase 3 data show an advantage over the cisplatin/pemetrexed standard, and the label safety information has not been reviewed. Other predicted indications (epithelioid, sarcomatoid and visceral pleural mesothelioma, breast carcinoma and rhabdomyosarcoma subtypes) have weaker evidence, mostly indirect or absent.

To proceed, the following is needed:

Review of the TGA Product Information for warnings, contraindications and approved indications (the ARTG indication text is missing)
Mechanism of action data
Comparative evidence against the current standard of care (cisplatin/pemetrexed, including immunotherapy-based regimens), ideally a randomised trial
A clinically meaningful position for oxaliplatin in a specific population, such as patients who cannot receive cisplatin or have progressed after pemetrexed
Safety planning for patients with renal, hepatic, neurological or lung conditions, and review of the Major interaction with dolasetron
Disclaimer

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