Dacarbazine
| Evidence Level: L4 | Predicted Indications: 1 |
Table of Contents
Dacarbazine: From Cancer Chemotherapy to Upper Aerodigestive Tract Neoplasm
One-Sentence Summary
Dacarbazine is an injectable DNA-alkylating chemotherapy agent that is marketed in the US as generic products. The TxGNN model predicts it may be effective for upper aerodigestive tract neoplasm, with a very high score of 99.26%. Evidence for this specific drug and indication is thin: 1 clinical trial and 19 publications were retrieved, but the trial tested a related drug (temozolomide) and none of the literature directly shows dacarbazine working in this indication.
Quick Overview
| Item | Content |
|---|---|
| Predicted New Indication | Upper aerodigestive tract neoplasm |
| TxGNN Prediction Score | 99.26% |
| Evidence Level | L4 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 4 records listed (3 unique ANDA numbers; all generics) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for dacarbazine is not available in the input. From general pharmacology, dacarbazine is a DNA-alkylating (methylating) agent. It is metabolically activated to MTIC, which damages tumor-cell DNA.
Temozolomide acts through the same MTIC species. The only linked clinical trial studied temozolomide in advanced aerodigestive tract cancers (head and neck, esophageal, non-small-cell lung, and colorectal) selected for MGMT promoter methylation. That gives class-level, indirect support for the idea that this type of alkylating agent may act in these tumors. It says nothing about dacarbazine itself.
The 99.26% TxGNN score is a computational prediction only, and it does not replace clinical evidence. The approved-indication text was not available in the input, so the link between dacarbazine’s labeled uses and this new indication could not be assessed.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00423150 | Phase 2 | Terminated | 86 | Temozolomide (not dacarbazine) in advanced aerodigestive tract, colorectal, and lung cancers selected for MGMT promoter methylation. The termination reason and efficacy results are not provided. |
This is indirect evidence only, because the study drug differs from dacarbazine and the record does not show a randomized design.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 41481311 | 2026 | RCT (Phase 3) | JAMA Oncology | Toripalimab vs dacarbazine as first-line therapy in acral melanoma. Dacarbazine was the comparator, in a different indication. |
| 23443801 | 2013 | Phase 2 trial | Molecular Cancer Therapeutics | Publication of NCT00423150: temozolomide in advanced aerodigestive tract and colorectal cancers with MGMT promoter methylation. This is a related drug, not dacarbazine. |
| 7826911 | 1994 | Clinical study | Annals of Oncology | Dacarbazine plus 5-fluorouracil chemotherapy in advanced medullary thyroid cancer. This is a neuroendocrine head-and-neck-region tumor, not an aerodigestive tract cancer. |
| 20627492 | 2010 | Review | Clinical Oncology | Overview of medullary thyroid carcinoma. |
| 25772801 | 2015 | Review | J Clin Neurosci | Temozolomide in aggressive pituitary tumors (related drug, different disease). |
| 12113649 | 2002 | Review | Am J Clin Dermatol | Current concepts in melanoma management. |
| 8346929 | 1993 | Review (Japanese) | Gan to Kagaku Ryoho | Chemotherapy for head and neck angiosarcoma, including the CYVADIC regimen, which contains dacarbazine. Prognosis remains extremely poor. |
| 34654328 | 2024 | Cohort (6 patients) | Ear, Nose & Throat Journal | Clinicopathological and genetic features of head and neck malignant paragangliomas. |
| 11163509 | 2001 | Retrospective cohort | Int J Radiat Oncol Biol Phys | Radiotherapy of esthesioneuroblastoma, a rare intranasal tumor. Radiotherapy only, not dacarbazine. |
Most of the retrieved literature is indirect: it involves a different drug, a different disease, or both. None of it shows dacarbazine efficacy in upper aerodigestive tract neoplasm.
US Market Information
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| ANDA075259 | Dacarbazine | Injection, powder, for solution | Meitheal Pharmaceuticals Inc. |
| ANDA075371 | Dacarbazine | Injection, powder, for solution | Fresenius Kabi USA, LLC |
| ANDA075812 | Dacarbazine | Injection, powder, lyophilized, for solution | Hikma Pharmaceuticals USA Inc. |
All products are injectable. One record (ANDA075371) appeared twice in the input and is listed once here.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (alkylating agent) |
| Myelosuppression Risk | Expected to be significant for this class. Please refer to the package insert for specifics. |
| Emetogenicity Classification | Moderate to high (typical for dacarbazine-type alkylators). Confirm against the package insert. |
| Monitoring Items | CBC with differential, liver and renal function |
| Handling Protection | Must follow cytotoxic drug handling regulations |
These entries are based on general drug-class knowledge, not on data in the Evidence Pack. Please refer to the package insert warnings and precautions.
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is very high, but the only linked trial tested temozolomide, was terminated, and has no efficacy conclusion. No dacarbazine-specific evidence exists for this indication, so the evidence level is L4.
To proceed, the following is needed:
- FDA package insert warnings and contraindications, which are required for any safety screening.
- Mechanism-of-action data for dacarbazine (for example, from DrugBank).
- Dacarbazine-specific clinical or preclinical evidence in upper aerodigestive tract tumors.
- The trial’s termination reason and results for NCT00423150, to judge how far the temozolomide class-level signal carries over.
- A clear definition of which tumor subtypes fall under “upper aerodigestive tract neoplasm”.
- Route compatibility assessment (dacarbazine is injectable only).
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.