Gemcitabine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Gemcitabine: From Ovarian Cancer to Female Breast Carcinoma
One-Sentence Summary
Gemcitabine is a nucleoside-analog chemotherapy drug, originally used for ovarian cancer and related ovarian tumours. The TxGNN model predicts it may be effective for female breast carcinoma, with 34 clinical trials and 20 publications currently retrieved for this direction, including completed Phase 3 trials.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Ovarian cancer (the Singapore licence records contain no approved indication text) |
| Predicted New Indication | Female breast carcinoma |
| TxGNN Prediction Score | 99.98% |
| Evidence Level | L1 (see note below) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 11 |
| Recommended Decision | Proceed with Guardrails |
Note on evidence level: Completed Phase 3 trials exist (NCT00006459, NCT00093795), which meets the L1 criterion by count. However, enrollment and results for NCT00006459 are not reported in the data compiled for this report. Several other Phase 3 trials have unknown status. The level should be confirmed against published trial results.
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the compiled data. Based on known information, gemcitabine is a nucleoside analog that inhibits DNA synthesis and ribonucleotide reductase. It is a cytotoxic drug that acts on rapidly dividing cells, so its action is not specific to one tumour type.
Its efficacy in ovarian cancer is established, and the same mechanism can plausibly apply to breast cancer. Reviews in the retrieved literature describe single-agent response rates of 16% to 37% in metastatic breast cancer. They also describe complementary activity with taxanes, platinum agents, anthracyclines and trastuzumab. The very high TxGNN score is consistent with this clinical picture.
Clinical Trial Evidence
The table lists the most relevant trials: completed Phase 3 and Phase 2 studies in breast cancer, plus a few others of interest.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00006459 | Phase 3 | Completed | Not reported | Gemcitabine plus paclitaxel vs paclitaxel in unresectable, locally recurrent or metastatic breast cancer |
| NCT00093795 | Phase 3 | Completed | 4894 | Adjuvant comparison of three regimens in node-positive breast cancer, including dose-dense AC followed by paclitaxel plus gemcitabine |
| NCT00408408 | Phase 3 | Unknown | 1206 | Neoadjuvant trial adding capecitabine or gemcitabine to docetaxel before AC, with or without bevacizumab |
| NCT00070278 | Phase 3 | Unknown | 800 | Neoadjuvant epirubicin/cyclophosphamide followed by paclitaxel with or without gemcitabine in poor-risk early breast cancer |
| NCT00039546 | Phase 3 | Unknown | Not reported | tAnGo: gemcitabine added to paclitaxel-containing, epirubicin-based adjuvant chemotherapy in ER/PgR-poor early breast cancer |
| NCT00003540 | Phase 2 | Completed | 30 | Single-agent gemcitabine in metastatic breast cancer previously treated with doxorubicin and paclitaxel |
| NCT00006007 | Phase 2 | Completed | 59 | Pemetrexed plus gemcitabine in metastatic breast cancer (single arm) |
| NCT00110084 | Phase 2 | Completed | 50 | Weekly nab-paclitaxel plus gemcitabine in metastatic breast cancer |
| NCT00244933 | Phase 2 | Completed | 19 | Gemcitabine plus genistein in metastatic breast cancer |
| NCT06027268 | Phase 2 | Active, not recruiting | 36 | Trilaciclib, pembrolizumab, gemcitabine and carboplatin in metastatic triple-negative breast cancer |
Literature Evidence
No randomised controlled trials were retrieved. The list below is mostly narrative reviews and clinical studies.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40779028 | 2025 | Phase I clinical study | Breast Cancer Res Treat | Carboplatin, gemcitabine and mifepristone in advanced breast and recurrent ovarian cancer |
| 15685819 | 2004 | Review | Oncology (Williston Park) | Gemcitabine plus paclitaxel in metastatic breast cancer; phase II response rate 52% (114 of 221 patients) |
| 15685821 | 2004 | Review | Oncology (Williston Park) | Gemcitabine plus platinum in metastatic breast cancer |
| 15685820 | 2004 | Review | Oncology (Williston Park) | Gemcitabine plus docetaxel in metastatic breast cancer |
| 14768404 | 2003 | Review | Oncology (Williston Park) | Gemcitabine, anthracycline and taxane combinations for advanced breast cancer |
| 12138397 | 2002 | Review | Semin Oncol | Single-agent response rates of 16% to 37%; higher with combinations |
| 12057045 | 2002 | Clinical study | Clin Breast Cancer | Neoadjuvant gemcitabine therapy for breast cancer |
| 14754469 | 2004 | Review | Clin Breast Cancer | Gemcitabine plus trastuzumab in HER2-overexpressing metastatic breast cancer |
| 16001951 | 2005 | Review | Expert Rev Anticancer Ther | Gemcitabine's mechanism (self-potentiation, masked chain termination, DNA repair inhibition) and Phase II activity in metastatic breast cancer |
| 12057039 | 2002 | Preclinical | Clin Breast Cancer | Gemcitabine with trastuzumab in breast and lung cancer cell lines |
Singapore Market Information
All 11 licences are valid single-ingredient injectables, and none carries approved indication text in the data compiled for this report. The table lists 5 of them.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN09416P | GEMZAR 200mg Powder for Solution for Infusion | Injection, powder, for solution | Not recorded |
| SIN13229P | GEMZAR 1gm Powder for Solution for Infusion | Injection, powder, for solution | Not recorded |
| SIN14925P | GEMITA Lyophilised Powder for Solution for Injection 200 mg/vial | Injection, powder, lyophilised | Not recorded |
| SIN15887P | GEMITA Concentrate for Solution for Infusion 38mg/ml | Infusion, solution concentrate | Not recorded |
| SIN14444P | Gemcitabine Sandoz Concentrate for Solution for Infusion 40mg/ml | Infusion, solution concentrate | Not recorded |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (nucleoside analog / antimetabolite) |
| Myelosuppression Risk | Medium to high. The knowledge graph links gemcitabine with leukopenia, thrombocytopenia and anaemia |
| Emetogenicity Classification | Low to moderate |
| Monitoring Items | Complete blood count with differential, liver and renal function |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Please refer to the package insert warnings and precautions for full details.
Safety Considerations
- Disease associations from the knowledge graph (not label text): kidney disease, liver disease, gallbladder disease, thrombocytopenia, leukopenia, anaemia (including macrocytic anaemia), interstitial lung disease, infectious disease, pyoureter, and haemolytic-uremic syndrome (including the typical form).
- Drug Interactions: 100 interactions were found in total. Of the 20 listed, naltrexone is rated Moderate and levofloxacin Minor. The rest (for example morphine, metformin, prednisone, simvastatin, aprepitant, palonosetron, vancomycin) have no severity rating.
- Case report: gemcitabine-induced retinopathy has been described in the literature (PMID 28961673).
Package insert warnings and contraindications could not be retrieved, so please refer to the package insert for authoritative safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Completed Phase 3 and several completed Phase 2 trials in breast cancer, supported by multiple reviews, make this a well-founded direction. The retrieved literature contains no RCT publications, and the safety label data are missing, so the proposal should advance only with controls.
To proceed, the following is needed:
- The package insert (warnings and contraindications) from the HSA website, which is a blocking gap for safety screening
- Published results of the Phase 3 trials (NCT00006459, NCT00093795) to confirm efficacy and the evidence level
- Detailed mechanism-of-action data from DrugBank
- Confirmation of the approved indications for the Singapore licences, since none are recorded
- A haematological monitoring plan and cytotoxic handling procedures
Other predicted indications (all lower priority):
- Endometrial mixed adenocarcinoma and endometrial mucinous adenocarcinoma have limited supporting evidence (L3, "Research Question"). That evidence concerns endometrial or ovarian cancer in general, not these subtypes.
- Rectum mucinous, colon mucinous, villoglandular endometrioid, cervical mucinous, gallbladder mucinous, rete ovarii, and mucin-rich endometrioid adenocarcinoma have no direct evidence (L4–L5, Hold).
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.