Procarbazine
| Evidence Level: L3 | Predicted Indications: 5 |
Table of Contents
Procarbazine: From Hodgkin Lymphoma to Follicular Lymphoma
One-Sentence Summary
Procarbazine is an oral alkylating-type chemotherapy agent, originally used to treat Hodgkin lymphoma. The TxGNN model predicts it may be effective for follicular lymphoma, but the supporting evidence is limited: 2 related clinical trials (neither directly demonstrating procarbazine efficacy) and 12 publications, mostly small series, reviews and older cohorts.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hodgkin lymphoma (including classic Hodgkin lymphoma and related subtypes). The India licence records contain no approved indication text. |
| Predicted New Indication | Follicular lymphoma |
| TxGNN Prediction Score | 0.9946 |
| Evidence Level | L3 |
| India Market Status | Listed in a compiled Indian medicine price dataset (5 of 5) – CDSCO approval status is not included in this data |
| Number of Listed Products | 5 (valid: 5) |
| Recommended Decision | Hold (research question) |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, procarbazine is an oral alkylating-type agent already used in lymphoma regimens such as those for Hodgkin lymphoma. Its efficacy in that setting is established, and mechanistically it may be applicable to other B-cell lymphomas such as follicular lymphoma.
The literature offers some support. A review titled “Procarbazine for non-Hodgkin’s lymphoma” describes two patients with relapsed or refractory follicular lymphoma who achieved a complete and durable remission with prolonged daily procarbazine. The PEP-C metronomic oral regimen (prednisone, etoposide, procarbazine, cyclophosphamide) has also been studied in relapsed or refractory lymphoma.
However, modern follicular lymphoma care relies on anti-CD20 antibody-based regimens. Procarbazine’s role today is unclear, and the evidence is limited to case-level reports and small studies.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00003113 | Phase 2 | Terminated | 6 | Oral combination chemotherapy with G-CSF in elderly patients with intermediate- or high-grade non-Hodgkin’s lymphoma. Procarbazine plausibly part of the regimen (to be verified). Terminated after 6 patients, so no meaningful efficacy evidence. |
| NCT00577993 | Phase 3 | Completed | 210 | Fludarabine, mitoxantrone and dexamethasone (FND) plus rituximab in stage IV indolent lymphoma. Procarbazine is not evident in the regimen, so this is useful only as a treatment-landscape comparator. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 16690522 | 2006 | Review / case report | Leuk Lymphoma | Two relapsed/refractory follicular lymphoma patients achieved complete, durable remission with prolonged daily procarbazine |
| 22507790 | 2012 | Cohort / Phase 2 | Hematology | PEP-C low-dose metronomic oral regimen (including procarbazine) for refractory/relapsed lymphoma |
| 11672513 | 2001 | RCT | J Hematother Stem Cell Res | Chemotherapy plus interferon-alpha2b versus chemotherapy alone in follicular lymphoma (procarbazine role not stated in the available abstract) |
| 1702144 | 1991 | Randomized trial | J Clin Oncol | ProMACE-CytaBOM superior to ProMACE-MOPP in advanced diffuse aggressive lymphoma (includes follicular large-cell histology; MOPP-type arm contains procarbazine) |
| 16230674 | 2005 | Review | J Clin Oncol | New treatment options have changed survival in follicular lymphoma |
| 12017536 | 2002 | Review | Oncology (Williston Park) | Role of mitoxantrone in non-Hodgkin’s lymphoma |
| 6370065 | 1984 | Cohort | Ann Intern Med | Prolonged initial remission in nodular mixed lymphoma treated with various regimens |
| 8426197 | 1993 | Cohort | J Clin Oncol | Clinical features and prognosis of follicular large-cell lymphoma |
| 2788716 | 1989 | Cohort | J Clin Oncol | Combination chemotherapy followed by involved-field radiotherapy in localized aggressive lymphomas |
| 6366124 | 1983 | Review | J Clin Oncol | Histologic conversion in non-Hodgkin’s lymphomas |
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 178891 | P Carzine 50mg Capsule (Alkem Laboratories Ltd) | Strip of 10 capsules | Not specified |
| 177184 | Procarb 50mg Tablet (Vhb Life Sciences Inc) | Strip of 10 tablets | Not specified |
| 250048 | Zinocarb 50mg Capsule (Miracalus Pharma Pvt Ltd) | Strip of 10 capsules | Not specified |
| 104228 | Hodpro 50mg Capsule (Neon Laboratories Ltd) | Strip of 10 capsules | Not specified |
| 153267 | Neozine 50mg Capsule (Vhb Life Sciences Inc) | Strip of 10 capsules | Not specified |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (alkylating-type agent) |
| Myelosuppression Risk | High. Knowledge-graph contraindication links include thrombocytopenia, leukopenia and anaemia, consistent with marrow toxicity. |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | CBC with differential and platelets, liver and renal function |
| Handling Protection | Follow cytotoxic drug handling regulations |
Safety Considerations
- Contraindication-related disease associations (knowledge graph, not label text): liver failure, liver disease, kidney disease, gallbladder disease, thrombocytopenia, leukopenia, anaemia (including macrocytic anaemia), blood coagulation disease, peripheral neuropathy and other peripheral nervous system disease, infectious disease (including fungal infection and dermatophytosis), pyoureter, and substance abuse/dependence.
- Drug Interactions: 433 interactions recorded. Major interactions in the data include isometheptene, bupropion, morphine, lorcaserin, diethylpropion, phentermine, fenfluramine, dexfenfluramine, mazindol, ephedrine, and the 5-HT3 antagonists dolasetron, palonosetron, ondansetron and granisetron. Moderate interactions include epinephrine (various forms) and metoclopramide. Levofloxacin is a minor interaction.
- Long-term risks: The literature shows procarbazine carcinogenicity in animal bioassays, and gonadal toxicity (including azoospermia) in survivors of procarbazine-containing regimens.
Package insert warnings and contraindications were not available; please refer to the package insert for label safety information.
Conclusion and Next Steps
Decision: Hold (research question)
Rationale: Evidence for follicular lymphoma is limited to a small case-level report, a metronomic regimen cohort, and older regimens, with no trial directly demonstrating procarbazine efficacy. Standard care now relies on anti-CD20-based regimens, and procarbazine carries significant marrow and long-term toxicity. The high TxGNN score is not yet supported by robust clinical data.
To proceed, the following is needed:
- Package insert warnings and contraindications from the India market labels (a blocking gap for safety screening)
- Mechanism of action data (e.g. from DrugBank)
- Verification of the regimen composition in NCT00003113
- Comparative evidence against current anti-CD20-based standards in follicular lymphoma
- Evaluation of the lower-ranked predictions (neuroblastoma, ganglioneuroblastoma, retroperitoneal neoplasm, and a rare vertebral/endocrine/T-cell syndrome), which have little or no clinical support at this stage
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.