Vincristine
| Evidence Level: L4 | Predicted Indications: 3 |
Table of Contents
Vincristine: From Established Oncology Indications to Ganglioneuroblastoma
One-Sentence Summary
Vincristine is a vinca-alkaloid chemotherapeutic agent widely used in combination regimens for pediatric and hematologic malignancies (specific original-indication text and MOA are not present in this evidence pack). The TxGNN model predicts it may be effective for Ganglioneuroblastoma, with 4 clinical trials and 6 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available — no India regulatory license records are on file for this drug in the evidence pack |
| Predicted New Indication | Ganglioneuroblastoma |
| TxGNN Prediction Score | 99.31% |
| Evidence Level | L4 |
| India Market Status | ✗ Not Marketed |
| Number of Registrations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in this evidence pack. Based on general pharmacological knowledge, vincristine is a vinca-alkaloid that binds tubulin and inhibits microtubule assembly, arresting cell division in mitosis. It is a long-standing component of combination chemotherapy regimens (e.g., VAC, CYVADIC, VCR-based induction) for a range of pediatric and hematologic malignancies.
Ganglioneuroblastoma is a neuroblastic tumor closely related biologically to neuroblastoma, and the evidence pack itself demonstrates that vincristine is already routinely used within multi-agent chemotherapy regimens for this tumor family. One literature entry (PMID 8255850) directly documents a spinal ganglioneuroblastoma achieving complete remission with a vincristine-containing regimen, and the Phase 3 trial NCT03126916 explicitly enrolls “high-risk neuroblastoma or ganglioneuroblastoma.” This existing real-world use pattern, rather than a novel biological hypothesis, is the primary support for the TxGNN prediction’s plausibility.
Because no original-indication text or DrugBank MOA data were retrievable in this pack, a formal mechanistic-similarity comparison between the original and predicted indications cannot yet be completed — this should be closed out with DrugBank/label data before final sign-off.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01798004 | Phase 1 | Completed | 150 | Busulfan/melphalan myeloablative consolidation after induction chemotherapy in newly diagnosed high-risk neuroblastoma |
| NCT06172296 | Phase 3 | Recruiting | 478 | Dinutuximab added to intensive multimodal therapy (induction chemo, surgery, radiation, transplant, immunotherapy) in newly diagnosed high-risk neuroblastoma |
| NCT03126916 | Phase 3 | Recruiting | 750 | 131I-MIBG or ALK inhibitor (lorlatinib) added to standard therapy in newly diagnosed high-risk neuroblastoma or ganglioneuroblastoma |
| NCT03786783 | Phase 2 | Active, not recruiting | 42 | Pilot induction regimen with dinutuximab + sargramostim combined with chemotherapy in newly diagnosed high-risk neuroblastoma |
Note: these trials primarily target the broader “high-risk neuroblastoma” spectrum; only NCT03126916 explicitly names ganglioneuroblastoma as an eligible diagnosis.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 8255850 | 1993 | Case report | Postgraduate Medical Journal | Unresectable spinal ganglioneuroblastoma achieved histologically confirmed complete remission with vincristine-containing combination chemotherapy (doxorubicin, cyclophosphamide, etoposide, ifosfamide, cisplatin) alone, without surgery or radiotherapy |
| 7421294 | 1980 | Case series | J Thorac Cardiovasc Surg | 31 patients with intrathoracic ganglioneuroblastoma treated with resection, radiation, and/or chemotherapy; long-term follow-up up to 25 years |
| 31342649 | 2019 | Prospective clinical trial | Pediatric Blood & Cancer | Image-defined risk factors used to guide timing of surgical resection in low-risk neuroblastoma, reducing treatment-related complications |
| 15701990 | 2005 | Case report | J Pediatr Hematol Oncol | Ganglioneuroblastoma presenting with obstructive jaundice, a rare initial feature of neuroblastic tumors |
| 8888754 | 1996 | Case report | J Pediatr Hematol Oncol | Stage 4 multifocal ganglioneuroblastoma with rare gastric involvement in an infant |
| 3071124 | 1988 | Case report | Hinyokika Kiyo | Multimodality treatment of adrenal ganglioneuroblastoma with giant regional lymph node metastasis |
India Market Information
Vincristine is currently not marketed in India according to the regulatory data in this evidence pack — no license or registration entries are on file (total_licenses: 0). No product-level table can be generated until India regulatory records are obtained.
Cytotoxicity
Vincristine is a conventional cytotoxic chemotherapy agent (vinca alkaloid class), so this section applies.
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (Vinca alkaloid, microtubule/mitotic inhibitor) |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Please refer to the package insert warnings and precautions |
| Handling Protection | Must follow standard cytotoxic/hazardous drug handling regulations |
Safety Considerations
Drug Interactions: DDI screening identified 505 total interactions. Notable examples include:
- Major: Clarithromycin
- Moderate: Aprepitant, Dexamethasone, Metronidazole, Eliglustat, Naltrexone, Glycerol phenylbutyrate, Miconazole, Rolapitant, Rosuvastatin, Simvastatin, Tinidazole, Troglitazone
- Minor: Levofloxacin
- Unknown severity (requires further review): Calcitriol, Pantoprazole, Clotrimazole, Morphine, Metformin, Omeprazole
Package-insert-level warnings and contraindications are not yet available in this evidence pack (flagged as a blocking data gap — see below).
Conclusion and Next Steps
Decision: Hold
Rationale: A blocking data gap exists — India/local product-label warnings and contraindications are not yet available, which prevents this candidate from entering the S1 safety pre-assessment stage. While the TxGNN score is high (99.31%) and existing literature/trials show vincristine is already used within combination regimens for neuroblastoma-spectrum tumors including ganglioneuroblastoma, no completed Phase 2/3 RCT specifically evaluates vincristine for ganglioneuroblastoma, and original indication/MOA data are also missing.
To proceed, the following is needed:
- India product label / TFDA-equivalent warnings and contraindications (DG001, Blocking)
- Confirmed mechanism of action from DrugBank API (DG002, High)
- Confirmed original indication list for the drug
- Route compatibility assessment (currently pending, not yet evaluated)
- Clarification of whether trial results for “high-risk neuroblastoma” (broad) can be reasonably extrapolated to ganglioneuroblastoma specifically, or whether ganglioneuroblastoma-specific outcome data is required
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.