Cytarabine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Cytarabine: From Acute Leukaemia to Small Cell Lung Carcinoma
One-Sentence Summary
Cytarabine is a pyrimidine nucleoside analogue chemotherapy drug, originally used for acute lymphoblastic and acute myeloid leukaemias. The TxGNN model predicts it may be effective for small cell lung carcinoma, but the data compiled for this report contain no registered clinical trials and no small-cell-specific clinical publications for this use. The evidence is limited to a model prediction, older non-small-cell lung cancer studies and laboratory work.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Acute lymphoblastic leukaemia and acute myeloid leukaemia (including several subtypes). The Singapore licence records contain no indication text, so this comes from the knowledge graph. |
| Predicted New Indication | Small cell lung carcinoma |
| TxGNN Prediction Score | 99.78% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data are not available in the data compiled for this report. Cytarabine is, however, a well-known pyrimidine nucleoside analogue that inhibits DNA synthesis in cells in S-phase. This makes a rapidly dividing tumour such as small cell lung carcinoma a plausible target in principle.
The original indications are acute leukaemias, where cytarabine is among the most effective agents. The literature compiled here also notes that many solid tumours are insensitive to it. This is partly attributed to high levels of cytidine deaminase, which breaks the drug down, and low levels of the activating enzyme.
The retrieved literature mainly concerns non-small cell lung cancer. It includes phase II trials of cytarabine plus cisplatin from 1990, which reported a response rate of about 14% with significant bone marrow toxicity. A 1987 report on high-dose cytarabine in small cell lung cancer is listed, but no abstract is available. The high TxGNN score is a prediction only and does not on its own show clinical benefit.
Clinical Trial Evidence
Currently no related clinical trials registered for small cell lung carcinoma.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 2156598 | 1990 | Phase II trial (NSCLC) | Cancer | High-dose cytarabine plus cisplatin in 37 patients with advanced NSCLC; response rate 14%; grade IV myelosuppression in 32%; 4 deaths on study |
| 2157307 | 1990 | Phase II trial (NSCLC) | Tumori | Cisplatin, vindesine and low-dose cytarabine in 32 patients with advanced NSCLC |
| 2158614 | 1990 | Randomised phase II (NSCLC) | Med Pediatr Oncol | Cisplatin-cytarabine versus cisplatin-vinblastine in 151 patients with advanced NSCLC |
| 3030547 | 1987 | Clinical report (SCLC) | Cancer Treat Rep | High-dose cytarabine in small cell lung cancer (no abstract available) |
| 1360876 | 1992 | In vitro cell-line study | Cancer Chemother Pharmacol | Drug sensitivity patterns in SCLC cell lines (focus on doxorubicin, etoposide and vincristine) |
| 1332622 | 1992 | Review | Gan To Kagaku Ryoho | Gemcitabine and DMDC, structurally related to cytarabine; many solid tumours are insensitive to cytarabine |
| 28223673 | 2017 | Case report | Gan To Kagaku Ryoho | Meningeal carcinomatosis with small cell lung carcinoma treated with a multidisciplinary approach |
| 2820740 | 1987 | Pilot study (NSCLC) | Eur J Cancer Clin Oncol | Cisplatin plus cytarabine in advanced NSCLC (no abstract available) |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN17149P | CYTARINE KABI SOLUTION FOR INJECTION OR INFUSION 100MG/ML | Injection, solution | Not stated in the licence record |
| SIN05521P | CYTARABINE SOLUTION FOR INJECTION 100 MG/ML | Injection | Not stated in the licence record |
| SIN14293P | CYBIN INJECTION 100mg/ml | Injection, solution, concentrate | Not stated in the licence record |
All three registrations are valid single-ingredient injectable products.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (pyrimidine nucleoside antimetabolite) |
| Myelosuppression Risk | High. Grade IV myelosuppression occurred in 32% of patients in a cytarabine-cisplatin NSCLC trial. |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Complete blood count with differential, liver and renal function |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Contraindication-related conditions (from the knowledge graph, not label text): kidney disease, liver disease, pancreatitis, gallbladder disease, thrombocytopenia, leukopenia, neutropenia, agranulocytosis, anaemia, peripheral neuropathy, fungal infection, diarrhoeal disease and pulmonary oedema, among others.
- Drug Interactions: The interaction search returned 100 records, and the entries reviewed are listed below.
- Moderate: naltrexone.
- Minor: levofloxacin.
- Severity not classified: mannitol, pantoprazole, glimepiride, doxycycline, clotrimazole, morphine, metformin, omeprazole, sucralfate, lansoprazole, vancomycin, atropine, lactulose, nizatidine, triamcinolone, prednisone, simvastatin and nystatin.
The package insert warnings and contraindications were not available, so please refer to the package insert for authoritative safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is very high, but no clinical trials exist for small cell lung carcinoma. The only direct small-cell publication is a 1987 report without an available abstract, and the other studies are in NSCLC or in vitro. Known marrow toxicity and the reported limited activity of cytarabine in solid tumours argue for caution.
To proceed, the following is needed:
- Retrieval and review of the 1987 small cell lung cancer study (PMID 3030547) for response and toxicity data
- Package insert warnings and contraindications from the HSA website
- Detailed mechanism-of-action data from DrugBank
- Preclinical evidence in SCLC models, including enzyme expression (deoxycytidine kinase and cytidine deaminase) and nucleoside transporter levels
- A comparison against current standard SCLC therapy before any trial design
Other predicted indications (for reference): Nine further indications were evaluated, and all are rated Hold except neuroblastoma, which is rated Research Question. All of these have indirect or no supporting evidence.
- Primary pulmonary lymphoma (L4, 99.78%): indirect evidence from high-dose methotrexate plus cytarabine regimens in primary CNS lymphoma.
- Well-differentiated fetal adenocarcinoma of the lung (L5, 99.76%): prediction only.
- Pulmonary blastoma (L5, 99.76%): prediction only.
- Upper aerodigestive tract neoplasm (L4, 99.49%): one randomised study of high-dose cytarabine with cisplatin and 5-FU in head and neck cancer (PMID 12110494).
- Ganglioneuroblastoma (L5, 99.36%): prediction only.
- Vertebral anomalies with endocrine and T-cell dysfunction (L5, 99.32%): prediction only, likely a graph artefact.
- Retroperitoneal neoplasm (L4, 99.23%): case reports of myeloid sarcoma and lymphoma only.
- Neuroblastoma (L4, 99.19%; Research Question): preclinical sensitivity data. The three listed trials do not test cytarabine for this disease.
- CLL/SLL with somatic hypermutation (L5, 98.96%): prediction only.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.