Gemcitabine
| Evidence Level: L5 | Predicted Indications: 8 |
Table of Contents
Gemcitabine: Rectum mucinous adenocarcinoma
One-Sentence Summary
Gemcitabine is a cytotoxic nucleoside analog originally used for ovarian cancer. The TxGNN model predicts it may be effective for rectum mucinous adenocarcinoma.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Rectum mucinous adenocarcinoma |
| TxGNN Prediction Score | 0.9977 |
| Evidence Level | L5 |
| Canada Market Status | Marketed (marketed DINs: 2 of 2) |
| Number of DINs | 2 (marketed: 2) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known information, gemcitabine is a nucleoside (pyrimidine) analog that inhibits DNA synthesis and ribonucleotide reductase. Its efficacy in ovarian cancer has been established, and this cytotoxic mechanism is not tissue-specific, so it may be applicable to breast carcinoma.
The link is supported by clinical experience. Gemcitabine combined with paclitaxel has shown activity in metastatic breast cancer, and reviews describe single-agent response rates of 16% to 37% and higher rates in combination with platinum agents, taxanes, vinorelbine or anthracyclines. The very high TxGNN score is consistent with this body of evidence.
Several trials also enrol breast and ovarian cancer patients together (for example, carboplatin, gemcitabine and mifepristone), which reflects the shared use of this drug across both tumour types.
Clinical Trial Evidence
The data include more than 30 trials. The most relevant are listed below. Three are Phase 3: the gemcitabine plus paclitaxel trial and two adjuvant/neoadjuvant trials. Only the first has a relevance grade of A, and its enrollment is not available in the data. Because of that missing detail, I could not confirm two completed Phase 3 RCTs, so the L1 level assigned in the source data should be checked.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00006459 | Phase 3 | Completed | N/A | Gemcitabine plus paclitaxel vs paclitaxel in unresectable, locally recurrent or metastatic breast cancer |
| NCT00093795 | Phase 3 | Completed | 4894 | Three adjuvant regimens in node-positive breast cancer, including dose-dense AC followed by paclitaxel plus gemcitabine |
| NCT00408408 | Phase 3 | Unknown | 1206 | Neoadjuvant capecitabine or gemcitabine added to docetaxel before AC, with or without bevacizumab |
| NCT00070278 | Phase 3 | Unknown | 800 | Neoadjuvant epirubicin/cyclophosphamide then paclitaxel with or without gemcitabine in poor-risk early breast cancer |
| NCT00039546 | Phase 3 | Unknown | N/A | tAnGo: gemcitabine added to paclitaxel/epirubicin-based adjuvant therapy in ER/PgR-poor early breast cancer |
| NCT00006007 | Phase 2 | Completed | 59 | Pemetrexed plus gemcitabine in metastatic breast cancer |
| NCT00110084 | Phase 2 | Completed | 50 | Nab-paclitaxel plus gemcitabine in metastatic breast cancer |
| NCT00244933 | Phase 2 | Completed | 19 | Gemcitabine plus genistein in stage IV breast cancer |
| NCT06027268 | Phase 2 | Active, not recruiting | 36 | Trilaciclib, pembrolizumab, gemcitabine and carboplatin in metastatic triple-negative breast cancer |
| NCT07528768 | Phase 2 | Not yet recruiting | 750 | Gemcitabine vs paclitaxel in women of African ancestry with metastatic triple-negative breast cancer |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40779028 | 2025 | Phase 1 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; response rate of 52% in phase II trials |
| 15685821 | 2004 | Review | Oncology (Williston Park) | Gemcitabine with platinum agents gives significant clinical benefit and response rates |
| 15685820 | 2004 | Review | Oncology (Williston Park) | Gemcitabine plus docetaxel, with partly non-overlapping toxicities |
| 14768404 | 2003 | Review | Oncology (Williston Park) | Gemcitabine, anthracycline and taxane combinations in advanced breast cancer |
| 12138397 | 2002 | Review | Semin Oncol | Single-agent response rates of 16% to 37%; role confirmed in about 20 phase II trials |
| 14754469 | 2004 | Review | Clin Breast Cancer | Gemcitabine plus trastuzumab in HER2-positive metastatic breast cancer |
| 12057045 | 2002 | Review | Clin Breast Cancer | Neoadjuvant gemcitabine in breast cancer |
| 12057039 | 2002 | Preclinical | Clin Breast Cancer | Gemcitabine and trastuzumab in breast and lung cancer cell lines |
| 28961673 | 2017 | Case report (adverse event) | Retina | Gemcitabine-induced retinopathy |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02412292 | GEMCITABINE INJECTION | Not stated | Not stated |
| 02402831 | GEMCITABINE INJECTION | Not stated | Not stated |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (nucleoside analog / antimetabolite) |
| Myelosuppression Risk | Medium to high. Knowledge-graph contraindication links include thrombocytopenia, leukopenia and anaemia, so haematological monitoring is important |
| 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 also refer to the package insert warnings and precautions.
Safety Considerations
- Contraindication signals from the knowledge graph (not label text): kidney disease, liver disease, gallbladder disease, thrombocytopenia, leukopenia, anaemia, macrocytic anaemia, interstitial lung disease, infectious disease, pyoureter, and haemolytic-uremic syndrome (including the typical form).
- Drug interactions: 100 interactions were recorded. The only graded ones are Naltrexone (Moderate) and Levofloxacin (Minor). The others are listed without a severity grade, including pantoprazole, omeprazole, lansoprazole, metformin, simvastatin, morphine, prednisone, aprepitant, palonosetron and vancomycin.
- Literature signal: a case report describes gemcitabine-induced retinopathy.
Please refer to the package insert for label warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Several Phase 2 and Phase 3 trials, plus multiple reviews, support gemcitabine-based regimens in breast cancer, and the drug is already marketed in Canada. The package insert safety information has not yet been reviewed, and the Canadian licences list no approved indication text, so the decision should be conditional.
To proceed, the following is needed:
- Review of Health Canada package insert warnings and contraindications
- Mechanism of action data from DrugBank
- Confirmation of the Phase 3 results (NCT00006459 enrollment and outcomes) to validate the evidence level
- Approved indication text and dosage forms for the two Canadian DINs
- A haematological monitoring plan, with attention to the myelosuppression signals
- A review of the interactions rated Moderate and the ungraded ones
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.