Gemcitabine
| Evidence Level: L5 | Predicted Indications: 8 |
Table of Contents
Gemcitabine: Rectum mucinous adenocarcinoma
One-Sentence Summary
Gemcitabine is a cytotoxic nucleoside analogue originally used to treat ovarian cancer. with 36 clinical trials and 20 publications currently supporting this direction, including Phase 3 trials of gemcitabine-containing regimens.
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 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the compiled data. Based on known pharmacology, gemcitabine is a nucleoside analogue that inhibits DNA synthesis. It does so by inhibiting ribonucleotide reductase and causing chain termination after it is incorporated into DNA. This cytotoxic action acts on rapidly dividing tumour cells.
Ovarian cancer and breast cancer are both common solid tumours in women, and both respond to DNA-damaging chemotherapy. Because gemcitabine’s mechanism does not depend on a tissue-specific target, it can reasonably apply to breast tumour cells. Gemcitabine plus paclitaxel is an established regimen in metastatic breast cancer, which is consistent with the TxGNN prediction.
Clinical Trial Evidence
The data include 36 trials. The 10 most relevant are listed below.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00006459 | Phase 3 | Completed | Not listed | Gemcitabine plus paclitaxel vs paclitaxel in unresectable, locally recurrent or metastatic breast cancer |
| NCT00093795 | Phase 3 | Completed | 4894 | Adjuvant regimens in node-positive breast cancer, including dose-dense AC followed by paclitaxel plus gemcitabine |
| NCT00039546 | Phase 3 | Unknown | Not listed | tAnGo: gemcitabine added to paclitaxel/epirubicin/cyclophosphamide adjuvant chemotherapy in ER/PgR-poor early breast cancer |
| 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 then paclitaxel with or without gemcitabine in poor-risk early breast cancer |
| NCT00006007 | Phase 2 | Completed | 59 | Pemetrexed plus gemcitabine in metastatic breast cancer |
| NCT00003540 | Phase 2 | Completed | 30 | Single-agent gemcitabine in metastatic breast cancer previously treated with doxorubicin and paclitaxel |
| NCT00110084 | Phase 2 | Completed | 50 | 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
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 15685819 | 2004 | Review | Oncology (Williston Park) | Gemcitabine plus paclitaxel in metastatic breast cancer; response rate was 52% across phase II trials |
| 15685821 | 2004 | Review | Oncology (Williston Park) | Gemcitabine with platinum compounds in metastatic breast cancer; clinical benefit and response rates reported |
| 15685820 | 2004 | Review | Oncology (Williston Park) | Gemcitabine plus docetaxel in metastatic breast cancer, based on complementary mechanisms and partly non-overlapping toxicity |
| 14768404 | 2003 | Review | Oncology (Williston Park) | Gemcitabine, anthracycline and taxane combinations in advanced breast cancer |
| 16001951 | 2005 | Review | Expert Rev Anticancer Ther | Gemcitabine is active in metastatic breast cancer alone and in combinations, with a favourable toxicity profile |
| 12138397 | 2002 | Review | Semin Oncol | Single-agent response rates of 16%-37% in metastatic breast cancer; nearly 20 phase II trials |
| 14754469 | 2004 | Review | Clin Breast Cancer | Gemcitabine plus trastuzumab in HER2-positive metastatic breast cancer |
| 12057045 | 2002 | Clinical study | Clin Breast Cancer | Neoadjuvant gemcitabine therapy for breast cancer |
| 12057039 | 2002 | Preclinical | Clin Breast Cancer | Gemcitabine with trastuzumab in breast and lung cancer cell lines |
| 24295415 | 2013 | Review | Future Oncol | Liposomal delivery of chemotherapeutics, using gemcitabine and paclitaxel as examples |
India Market Information
All 20 registrations are valid single-ingredient injectable products. The five below are examples. The records contain no approved-indication text.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 99309 | Gemcitapar 200mg Injection | Vial of 1 injection | Not stated in the records |
| 16075 | Abingem 1000mg Injection | Vial of 1 powder for injection | Not stated in the records |
| 98788 | Gemciglan 1gm Injection | Vial of 1 injection | Not stated in the records |
| 98818 | Gembine 1000mg Injection | Vial of 1 injection | Not stated in the records |
| 38121 | Cytogem 1000mg Injection | Vial of 1 injection | Not stated in the records |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (pyrimidine nucleoside antimetabolite) |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Complete blood count, liver function and kidney function |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Contraindication-related conditions (knowledge graph): kidney disease, liver disease, gallbladder disease, thrombocytopenia, leukopenia, anaemia (including macrocytic anaemia), interstitial lung disease, infectious disease, pyoureter, and hemolytic-uremic syndrome (including the typical form). These come from drug-disease relationships in the knowledge graph, not from label text.
- Drug Interactions: 339 interactions are recorded. The only graded ones in the first 20 listed are naltrexone (moderate) and levofloxacin (minor). The others in that list have no grade, including calcitriol, doxycycline, pantoprazole, glimepiride, morphine, metformin and omeprazole.
- Reported adverse events in the literature: a case report of gemcitabine-induced retinopathy.
Package insert warnings and contraindications were not available for this report. Please refer to the package insert for the full safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Several Phase 3 trials of gemcitabine-containing regimens in breast cancer, together with multiple Phase 2 studies and reviews, support this prediction. The Phase 3 trials are combination studies, and several have an unknown status, so the L1 level rests mainly on the completed trials NCT00006459 and NCT00093795. The haematological and organ-related safety signals call for careful monitoring.
To proceed, the following is needed:
- Package insert warnings and contraindications from the India regulatory source, which are currently missing
- Detailed mechanism of action data
- Published results and the enrolment figure for the Phase 3 trial NCT00006459
- Confirmation of whether breast cancer is an approved indication for the India registrations
- Subtype-specific evidence, such as triple-negative disease, and a safety monitoring plan for patients with kidney, liver or bone marrow impairment
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.