Mercaptopurine
| Evidence Level: L3 | Predicted Indications: 8 |
Table of Contents
Mercaptopurine: Myeloid leukemia
One-Sentence Summary
Mercaptopurine is a purine antimetabolite used as a cytotoxic chemotherapy agent in leukemia. The TxGNN model predicts it may be effective for myeloid leukemia, with a prediction score of 0.9994. The data compiled for this report include 15 clinical trials and 20 publications, but most trials test multi-drug regimens, so the evidence level is L3.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Myeloid leukemia |
| TxGNN Prediction Score | 0.9994 |
| Evidence Level | L3 |
| India Market Status | Listed in a compiled Indian medicine price dataset (7 of 7) – CDSCO approval status is not included in this data |
| Number of Listed Products | 7 (valid: 7) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Mercaptopurine is a purine antimetabolite. Its thioguanine nucleotide metabolites are incorporated into DNA and RNA and inhibit de novo purine synthesis. This is toxic to rapidly dividing cells such as leukemic blasts. Detailed mechanism-of-action data are not otherwise available in the compiled data, so this description rests on the general pharmacology of the drug class.
Myeloid leukemia is a blood cancer that, like lymphoid leukemia, depends on rapid cell division, so an agent that disrupts purine synthesis is mechanistically plausible. Published reports support this direction. A cohort study gave oral 6-mercaptopurine with methotrexate as maintenance therapy to acute myeloid leukemia patients who could not have a transplant (PMID 26425037). A prospective pilot study tested low-dose metronomic oral 6-mercaptopurine in elderly acute myeloid leukemia (PMID 27275453).
The evidence is capped at L3. No randomized trial isolates mercaptopurine as the variable. The Phase 3 trials listed are multi-drug regimens, so mercaptopurine’s own contribution cannot be separated out.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00003934 | Phase 3 | Completed | 420 | Acute promyelocytic leukemia. Maintenance with intermittent tretinoin plus mercaptopurine and methotrexate versus tretinoin alone; arsenic trioxide added in consolidation |
| NCT06199557 | Phase 1/2 | Recruiting | 48 | Hydroxyurea or 6-mercaptopurine combined with valproic acid in AML or high-risk MDS patients unfit for standard therapy |
| NCT05506332 | Phase 1 | Recruiting | 10 | Venetoclax plus 6-mercaptopurine in relapsed or refractory AML |
| NCT00492856 | Phase 3 | Completed | 105 | Maintenance versus observation in low- and intermediate-risk acute promyelocytic leukemia (S0521) |
| NCT02521493 | Phase 3 | Active, not recruiting | 280 | Risk-stratified therapy for AML in Down syndrome; the role of mercaptopurine is not confirmed |
| NCT02688140 | Phase 3 | Completed | 133 | Arsenic trioxide with ATRA and idarubicin versus AIDA in high-risk acute promyelocytic leukemia |
| NCT00482833 | Phase 3 | Completed | 276 | Arsenic trioxide with ATRA versus AIDA in non-high-risk acute promyelocytic leukemia |
| NCT00136084 | Phase 3 | Completed | 238 | Two multi-agent regimens with different cytarabine doses in newly diagnosed AML or myelodysplasia |
| NCT00866918 | Phase 3 | Completed | 106 | Risk-adapted treatment with arsenic trioxide in childhood acute promyelocytic leukemia |
| NCT00551460 | Phase 2 | Completed | 78 | ATRA, arsenic trioxide and gemtuzumab in high-risk acute promyelocytic leukemia |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 26425037 | 2015 | Cohort | Journal of Korean Medical Science | Oral 6-mercaptopurine and methotrexate maintenance in transplant-ineligible AML patients in first remission |
| 27275453 | 2016 | Prospective pilot | South Asian Journal of Cancer | Metronomic oral 6-mercaptopurine in elderly AML |
| 38828002 | 2024 | Cohort | Therapeutic Advances in Hematology | Dual induction with ALL-like consolidation in childhood AML at multiple Chinese centres |
| 32459546 | 2020 | Retrospective | Pediatric Hematology and Oncology | Sequential cytarabine and 6-mercaptopurine in juvenile myelomonocytic leukemia |
| 22715121 | 2012 | Phase 2 trial | Blood | ATRA, idarubicin and arsenic trioxide as initial therapy in acute promyelocytic leukemia |
| 33183436 | 2021 | Review | Journal of Nanoscience and Nanotechnology | 6-mercaptopurine nanomedicine in leukemia treatment |
| 12057059 | 2000 | Review | Current Treatment Options in Oncology | Treatment of acute promyelocytic leukemia |
| 34442422 | 2021 | Review | Journal of Personalized Medicine | NUDT15 polymorphisms and thiopurine toxicity |
| 3513537 | 1986 | Clinical study | American Journal of Clinical Oncology | Hydroxyurea with 6-mercaptopurine in chronic granulocytic leukemia |
| 2676034 | 1989 | Review | Blood Reviews | Purine metabolism as a target for leukemia chemotherapy |
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 144363 | Merkglob 50mg Tablet | Strip of 10 tablets | Not stated in the compiled data |
| 180387 | Puri Nethol 50mg Tablet | Strip of 10 tablets | Not stated in the compiled data |
| 81393 | Empurine 50mg Tablet | Strip of 10 tablets | Not stated in the compiled data |
| 41061 | Captomer 50mg Tablet | Strip of 10 tablets | Not stated in the compiled data |
| 180830 | Purinetone 50mg Tablet | Strip of 10 tablets | Not stated in the compiled data |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (purine antimetabolite) |
| Myelosuppression Risk | High; neutropenia, thrombocytopenia, leukopenia and anaemia are listed as concerns in the compiled data |
| Emetogenicity Classification | Low |
| Monitoring Items | Complete blood count with differential, liver function, renal function, bilirubin |
| Handling Protection | Follow cytotoxic drug handling regulations |
Safety Considerations
- Conditions of concern: The compiled data list kidney disease, liver disease, pancreatitis, gallbladder disease, cholestasis, hyperbilirubinemia (including Gilbert syndrome), thrombocytopenia, neutropenia, leukopenia, agranulocytosis, anaemia and hepatosplenic T-cell lymphoma. These come from drug–disease relation data, not from label text, and should be checked against the package insert.
- Drug Interactions: 296 interacting drugs are recorded. Moderate-level interactions include mesalazine, balsalazide, olsalazine, sulfasalazine and naltrexone. Levofloxacin is rated minor.
- Pharmacogenetic variation in thiopurine-metabolising enzymes (TPMT, NUDT15) affects the risk of severe bone marrow suppression (PMID 34442422).
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Cohort and pilot data support oral mercaptopurine maintenance in acute myeloid leukemia, and several Phase 3 trials cover leukemia regimens. However, no randomized trial tests mercaptopurine itself in myeloid leukemia, so the evidence is level L3 and should be treated as a research question.
To proceed, the following is needed:
- A trial or analysis that isolates mercaptopurine’s contribution in myeloid leukemia
- Package insert warnings and contraindications for the Indian-marketed products
- A safety monitoring plan covering blood counts and TPMT/NUDT15 genotyping
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.