Cytarabine
| Evidence Level: L4 | Predicted Indications: 9 |
Table of Contents
Cytarabine: From Antimetabolite Chemotherapy to Small Cell Lung Carcinoma
One-Sentence Summary
Cytarabine is a cytotoxic pyrimidine antimetabolite that is marketed in the US as an injectable. The TxGNN model predicts it may be effective for small cell lung carcinoma (SCLC), with a very high score. However, the supporting evidence is indirect: 3 registered trials (none testing cytarabine in SCLC) and 20 publications, mostly older, small studies.
Quick Overview
| Item | Content |
|---|---|
| Predicted New Indication | Small cell lung carcinoma |
| TxGNN Prediction Score | 99.78% |
| Evidence Level | L4 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 15 (the listed products are ANDA generics) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, cytarabine is an S-phase pyrimidine antimetabolite. It interferes with DNA synthesis in rapidly dividing cells. Mechanistically, this may be applicable to a fast-proliferating tumour such as SCLC.
SCLC is highly proliferative and often chemosensitive at first, so a cell-cycle-specific antimetabolite is biologically plausible. The high TxGNN score (0.998) partly reflects this.
The clinical data, however, are indirect. The listed trials concern non-small cell lung cancer (NSCLC) or intrathecal pemetrexed, not cytarabine in SCLC. The older SCLC literature consists of small studies in which cytarabine was added to other chemotherapy or used as a single agent. These reports do not establish efficacy.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03101579 | Phase 1 | Completed | 13 | Intrathecal pemetrexed for NSCLC leptomeningeal metastasis. Different drug and histology (relevance C). |
| NCT00863512 | Phase 3 | Terminated | 34 | Adjuvant chemotherapy vs observation in early-stage NSCLC. Cytarabine’s role is not evident (relevance C). |
| NCT03507244 | Phase 1/2 | Completed | 34 | Intrathecal pemetrexed plus radiotherapy for leptomeningeal metastasis from solid tumours. Not cytarabine and not SCLC (relevance C). |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 232239 | 1979 | Clinical study (SCLC) | Med Pediatr Oncol | 20 untreated SCLC patients received cyclophosphamide, Adriamycin and subcutaneous cytarabine, plus thoracic and whole-brain radiotherapy. |
| 6095640 | 1984 | Clinical study (SCLC) | Am J Clin Oncol | Continuous-infusion Ara-C alone in 10 heavily pretreated patients gave no responses and severe toxicity. A second study added Ara-C to CAV in 25 extensive-stage patients. |
| 2841844 | 1988 | Clinical study (SCLC) | Am J Clin Oncol | VP-16 plus infusional Ara-C in 17 patients with relapsed SCLC. Three early deaths were due to progressive tumour. |
| 6264785 | 1981 | Case series | Am J Med | Meningeal carcinomatosis as a complication in 60 patients with SCLC receiving intensive chemotherapy. |
| 28223673 | 2017 | Case report | Gan To Kagaku Ryoho | SCLC with meningeal carcinomatosis managed with a multidisciplinary approach. |
| 11331076 | 2001 | Preclinical | Biochem Pharmacol | Drug-resistant SCLC cell lines showed collateral sensitivity to gemcitabine and cytarabine. |
| 2156598 | 1990 | Phase II (NSCLC) | Cancer | High-dose cytarabine plus cisplatin in 37 NSCLC patients gave a 14% response rate. Grade IV myelosuppression occurred in 32%. |
| 2157307 | 1990 | Phase II (NSCLC) | Tumori | Cytarabine, cisplatin and vindesine in 32 advanced NSCLC patients. |
| 2820740 | 1987 | Pilot study (NSCLC) | Eur J Cancer Clin Oncol | Cisplatin plus cytarabine pilot in advanced NSCLC. |
| 9561978 | 1998 | Review/Case series | Arch Neurol | Combined-modality therapy for carcinomatous meningitis secondary to NSCLC. |
US Market Information
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| ANDA208485 | Cytarabine | Injection, solution | Meitheal Pharmaceuticals Inc. |
| ANDA075383 | Cytarabine | Injection, solution | Hospira, Inc. |
| ANDA072945 | Cytarabine | Injection, solution | Hospira, Inc. |
| ANDA206189 | Cytarabine | Injection, solution | Meitheal Pharmaceuticals Inc. |
A lyophilized powder injection form is also recorded for the drug.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (pyrimidine antimetabolite, S-phase specific) |
| Myelosuppression Risk | High. In a high-dose cytarabine plus cisplatin study, grade IV myelosuppression occurred in 32% and grade III in 14% of patients. Severe toxicity was also reported in heavily pretreated SCLC patients. |
| Emetogenicity Classification | Not specified in the data. Nausea and vomiting were a principal non-haematological toxicity in the literature. |
| Monitoring Items | CBC with differential, liver and renal function |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score is very high, but no trial tests cytarabine in SCLC. The three registered trials are all relevance grade C, and the SCLC literature is limited to small, decades-old studies. Cytarabine is not part of current SCLC practice in this evidence set, and the toxicity burden is substantial. A rank-2 prediction (primary pulmonary lymphoma) is flagged as a research question because cytarabine is an established component of lymphoma regimens. That evidence is class-level rather than disease-specific.
To proceed, the following is needed:
- Package insert warnings and contraindications, which currently block safety screening
- Mechanism of action data (e.g., from DrugBank)
- Full-text review of the older SCLC studies for response rates, survival and toxicity
- Comparison against current SCLC standard-of-care regimens
- Any modern prospective data on cytarabine in SCLC, or a preclinical study to support one
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any clinical use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.