Cytarabine
| 證據等級: L5 | 預測適應症: 9 個 |
目錄
Cytarabine: From Acute Myeloid Leukemia to Small Cell Lung Carcinoma
One-Sentence Summary
Cytarabine (Ara-C) is a pyrimidine nucleoside antimetabolite long established as a backbone agent for acute myeloid leukemia and other hematologic malignancies. The TxGNN model predicts it may be effective for Small Cell Lung Carcinoma (SCLC), with 3 clinical trials (none directly testing cytarabine) and 20 publications, largely from the 1970s–1990s, currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in local regulatory data (drug is not marketed locally); globally established for acute myeloid leukemia and other hematologic malignancies |
| Predicted New Indication | Small Cell Lung Carcinoma |
| TxGNN Prediction Score | 99.78% |
| Evidence Level | L3 |
| Norway Market Status | 未上市 (Not Marketed) |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, cytarabine is a cell-cycle (S-phase) specific pyrimidine nucleoside analog that incorporates into DNA and inhibits DNA polymerase, and its efficacy in acute leukemia has been proven for decades. Mechanistically it has also been explored — mostly in older literature — for solid tumors with rapid proliferation, including lung cancer.
Small cell lung carcinoma is characterized by a very high growth fraction, which in principle makes it a plausible target for an S-phase-specific cytotoxic agent like cytarabine. Historical combination regimens (e.g., cyclophosphamide/doxorubicin/cytosine arabinoside plus radiotherapy, and cytarabine plus cisplatin/vindesine) were tested in NSCLC and SCLC in the late 1970s through 1990s, showing measurable but modest activity, often limited by significant hematologic toxicity.
However, none of the clinical trials currently linked to this prediction directly test cytarabine — they primarily evaluate intrathecal pemetrexed or unrelated NSCLC adjuvant regimens. The supporting mechanistic rationale therefore relies on older cohort/pilot studies rather than modern, disease-specific trial designs, which limits confidence in this prediction.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03507244 | Phase 1/2 | Completed | 34 | Intrathecal pemetrexed with concurrent involved-field radiotherapy for leptomeningeal metastasis from solid tumors; does not test cytarabine, disease overlap only |
| NCT03101579 | Phase 1 | Completed | 13 | Intrathecal pemetrexed for recurrent leptomeningeal metastasis from NSCLC; cytarabine mentioned only as a comparator class, not tested |
| NCT00863512 | Phase 3 | Terminated | 34 | Adjuvant chemotherapy (vinorelbine, cisplatin, docetaxel, gemcitabine, pemetrexed) in early-stage NSCLC; cytarabine not part of regimen, trial terminated |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 2157307 | 1990 | Phase 2 trial | Tumori | Cytarabine + cisplatin + vindesine in 32 advanced NSCLC patients; 18% response rate |
| 2156598 | 1990 | Phase 2 trial | Cancer | High-dose cytarabine + cisplatin in 37 chemo-naive NSCLC patients; 14% response rate, Grade III/IV myelosuppression in 46% |
| 2820740 | 1987 | Pilot trial | Eur J Cancer Clin Oncol | Cisplatin + cytarabine combination pilot study in advanced NSCLC |
| 232239 | 1979 | Cohort/combined modality | Med Pediatr Oncol | 20 SCLC patients treated with cyclophosphamide/Adriamycin + subcutaneous cytosine arabinoside plus radiotherapy |
| 6095640 | 1984 | Historical trial | Am J Clin Oncol | Continuous-infusion Ara-C alone (no response, severe toxicity) and Ara-C added to CAV regimen in SCLC |
| 2841844 | 1988 | Historical trial | Am J Clin Oncol | Etoposide + infusional Ara-C in relapsed/refractory SCLC (17 patients) |
| 348088 | 1978 | Review | Antibiot Chemother | Review of Ara-C analogs and strategies to prolong biological activity against cytidine deaminase deactivation |
| 9561978 | 1998 | Case series | Arch Neurol | Combined modality therapy for carcinomatous meningitis secondary to NSCLC |
| 6264785 | 1981 | Case report | Am J Med | Meningeal carcinomatosis in SCLC patients receiving intensive chemotherapy |
| 28223673 | 2017 | Case report | Gan To Kagaku Ryoho | Multidisciplinary treatment of meningeal carcinomatosis in SCLC |
Norway Market Information
This drug currently has no marketing authorizations recorded in the reviewed regulatory data (market status: 未上市 / Not Marketed, 0 authorizations).
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (pyrimidine nucleoside antimetabolite / S-phase-specific antileukemic agent) |
| Myelosuppression Risk | High — historical NSCLC combination data report Grade IV myelosuppression in 32% and Grade III in 14% of patients treated with high-dose cytarabine + cisplatin |
| Emetogenicity Classification | Moderate to High (dose-dependent; nausea/vomiting reported as principal non-hematologic toxicity in high-dose regimens) |
| Monitoring Items | CBC with differential, liver and renal function, neurological exam (high-dose neurotoxicity), ocular exam (conjunctivitis risk with high-dose regimens) |
| 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: A blocking data gap exists — local prescribing warnings/contraindications are unavailable, which prevents entry into S1 safety pre-assessment. In addition, none of the linked clinical trials directly test cytarabine for SCLC, and the supporting evidence is largely historical (1970s–1990s) with modest efficacy and significant myelosuppression; the drug is also not currently marketed locally.
To proceed, the following is needed:
- Local product label / regulatory safety data (warnings, contraindications, DDI) — currently blocking
- Detailed mechanism of action (MOA) data from DrugBank
- Modern, disease-specific clinical evidence directly evaluating cytarabine in SCLC (current linked trials do not test the drug)
- Route of administration compatibility assessment
- Local market/import pathway assessment given current "not marketed" status
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.