Cisplatin
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Cisplatin: From Ovarian Cancer to Female Breast Carcinoma
One-Sentence Summary
Cisplatin is a platinum-based chemotherapy drug, originally used to treat ovarian cancer and related ovarian tumours. The TxGNN model predicts it may be effective for female breast carcinoma, with 20 clinical trials and 20 publications compiled for this direction. Most trials are indirect, and only a few compare cisplatin directly.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Ovarian cancer (approved indication text not available in the Singapore licence records) |
| Predicted New Indication | Female breast carcinoma |
| TxGNN Prediction Score | 97.39% |
| Evidence Level | L2 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Hold |
Note: The data compiled for this report also covers nine other predicted indications. This report focuses on the top-ranked prediction (female breast carcinoma) and mentions the others briefly in the conclusion.
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available. Based on known pharmacology, cisplatin forms DNA crosslinks that cause replication stress and cell death (apoptosis). This effect is especially relevant in tumours with defective homologous recombination DNA repair, such as those with BRCA1/2 or PALB2 mutations, and in triple-negative breast cancer.
Ovarian cancer and breast cancer share a biological link through BRCA-related DNA repair deficiency. The original indication list even includes hereditary breast ovarian cancer syndrome. Tumours that cannot repair DNA crosslinks should be more sensitive to platinum drugs, which supports the model's prediction. The cited literature on PALB2 and on cisplatin response in breast tumours is consistent with this reasoning.
Clinical Trial Evidence
The table lists the trials most relevant to cisplatin in breast cancer. Many of the other trials compiled are early-phase studies of new agents or high-dose regimens where cisplatin's own contribution cannot be isolated.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01670500 | Phase 2 | Completed | 118 | Neoadjuvant cisplatin vs. doxorubicin/cyclophosphamide in newly diagnosed breast cancer with germline BRCA mutations; direct comparison of cisplatin (no results summarised in the data) |
| NCT03201861 | Phase 3 | Recruiting | 762 | Weekly paclitaxel plus cisplatin as adjuvant chemotherapy in high-risk, HER2-negative early breast cancer; no results yet |
| NCT02365805 | Phase 2 | Completed | 30 | Neoadjuvant chemotherapy tailored by BRCA1 levels in HER2-negative breast cancer; small study |
| NCT00003032 | Phase 3 | Completed | 224 | High-dose chemotherapy with stem cell support vs. standard therapy in metastatic breast cancer; cisplatin is likely one component, and the approach is dated |
| NCT00535509 | Not specified | Completed | 285 | Neoadjuvant FEC100/cisplatin-docetaxel with or without trastuzumab in HER2-positive locally advanced breast cancer |
| NCT00002836 | Phase 3 | Completed | 184 | High-dose chemotherapy with G-CSF for stem cell mobilisation in metastatic or high-risk breast cancer |
| NCT00002772 | Phase 3 | Terminated | 602 | Intensive sequential chemotherapy vs. high-dose chemotherapy with stem cell support in primary breast cancer |
| NCT02897375 | Phase 1 | Completed | 71 | Palbociclib with cisplatin or carboplatin in advanced solid tumours |
| NCT02658214 | Phase 1 | Completed | 32 | Durvalumab and tremelimumab with first-line chemotherapy, including triple-negative breast cancer |
| NCT00002854 | Phase 1 | Completed | 33 | Pilot of sequential high-dose combination chemotherapy including cisplatin; cisplatin's contribution cannot be isolated |
Literature Evidence
No randomised controlled trials were found in the compiled breast cancer literature. The items below are mostly reviews, small clinical series and preclinical studies.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 2643295 | 1989 | Clinical series | Am J Clin Oncol | Cisplatin plus etoposide in 31 patients with refractory metastatic breast cancer: 3 complete and 8 partial responses among 29 evaluable patients |
| 39216513 | 2024 | Review | Mutat Res Rev Mutat Res | Molecular determinants of cisplatin response and resistance in breast tumours, and nanotechnology-based strategies |
| 39536542 | 2024 | Review | Pathol Res Pract | Role of lncRNAs in cisplatin response and resistance in breast cancer |
| 27448297 | 2016 | Review | Tumour Biol | miRNA-mediated cisplatin resistance in breast cancer |
| 34998857 | 2022 | Preclinical | Toxicol Appl Pharmacol | Timed (chronotherapy) cisplatin in a mouse model of triple-negative mammary carcinoma |
| 41053085 | 2025 | Preclinical | Cell Death Dis | USP9X and WWP1 regulate IGF2BP2 and affect triple-negative breast cancer progression and cisplatin sensitivity |
| 37067747 | 2023 | Preclinical | Cell Oncol | Gallium maltolate is synergistic with cisplatin in breast carcinoma cells |
| 37914960 | 2024 | Preclinical | Breast Cancer | SLC38A5 promotes glutamine metabolism and reduces cisplatin chemosensitivity |
| 32066812 | 2020 | Preclinical | Sci Rep | Nano-graphene oxide carrying cisplatin and doxorubicin improves anticancer activity |
| 8400329 | 1993 | Clinical pharmacology | Breast Cancer Res Treat | Pharmacokinetic and pharmacodynamic interactions of intensive cyclophosphamide, cisplatin and BCNU in breast cancer |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN00762P | DBL Cisplatin Injection 1 mg/ml (Hospira Australia) | Injection | Not available in the licence records |
| SIN05418P | Cisplatin Injection 1 mg/ml (Bridgewest Perth Pharma) | Injection | Not available in the licence records |
Both registrations are valid single-ingredient products with no cancelled licences.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (platinum-based DNA-crosslinking agent) |
| Myelosuppression Risk | Medium to high; please refer to the package insert warnings and precautions |
| Emetogenicity Classification | High |
| Monitoring Items | Complete blood count with differential, renal function, electrolytes (including magnesium), liver function, and hearing assessment |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Drug Interactions: The interaction screening returned 100 interacting drugs in total, and the first 20 are listed in the data compiled for this report. Almost all are rated Moderate, with one Minor (ascorbic acid). The main groups are:
- Proton pump inhibitors (rabeprazole, omeprazole, esomeprazole, lansoprazole, dexlansoprazole)
- Corticosteroids (hydrocortisone, dexamethasone, triamcinolone, betamethasone, beclomethasone)
- Amphotericin B products (conventional, lipid complex, cholesteryl sulfate, liposomal)
- Mesalazine and balsalazide
- Metronidazole, exenatide and kanamycin
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: Mechanistically, cisplatin is plausible for breast cancer, especially BRCA/PALB2-related and triple-negative disease. However, the direct evidence consists of one small-to-moderate completed Phase 2 trial (NCT01670500, no results summarised) and one ongoing Phase 3 trial without results. There are no breast-specific RCT publications. In addition, the Singapore package insert warnings and contraindications are not available, so safety screening cannot be completed.
To proceed, the following is needed:
- Results of NCT01670500 and, when available, NCT03201861
- Singapore package insert warnings and contraindications (download and review the HSA documents)
- Detailed mechanism of action data
- Approved indication text for the two Singapore registrations
- Definition of the target population (e.g., BRCA-mutated or triple-negative breast cancer) and a plan for monitoring toxicity
Other predicted indications in the compiled data:
- Choriocarcinoma of ovary, gonadal germ cell tumour, adult germ cell tumour (L1, Proceed with Guardrails): these have many Phase 2/3 trials of cisplatin-based regimens such as BEP, and they are close to the existing ovarian indications. They may be stronger repurposing candidates than breast carcinoma.
- Ovarian primitive germ cell tumour (L3, Proceed with Guardrails): the evidence is mostly extrapolated from the wider germ cell tumour trials.
- Five testicular yolk sac tumour histologic patterns (L5, Hold): model prediction only, with no trials or literature.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.