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Bending the Curve Trial by Trial
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Nitrosoureas, triazenes, alkyl sulfonates, aziridines and related alkylatorsIn useSynthetic

Procarbazine

Also known as Matulane

An oral methylhydrazine. The current US label lists it, with other anticancer drugs, for Stage III or IV Hodgkin lymphoma. It is also the P in the PCV regimen for gliomas.

From discovery to approval

  1. 1963 · Earliest report found

    A 2007 review says procarbazine was first synthesised in the late 1950s during a search for a new monoamine oxidase inhibitor and soon developed as an anticancer agent. The earliest paper found, by W. Bollag and E. Grunberg in 1963, reports tumour-inhibiting methylhydrazine derivatives.[2][3][4][5]

  2. 1969-07-22 · FDA regular · 6 years after first description

    Procarbazine hydrochloride capsules (Matulane), NDA 016785, original approval, classed as a new molecular entity with priority review in the Drugs@FDA history. The original label is not available there, so the indication at approval is not stated here; the current label lists Stage III or IV Hodgkin lymphoma in combination with other anticancer drugs. The type regular is an inference: no accelerated-approval wording was found.[6]

How it works

The US label says the precise mode of action is not clearly defined. After metabolic activation it may inhibit methyl transfer into transfer RNA, blocking protein, DNA and RNA synthesis, and auto-oxidation may form free radicals that damage DNA by alkylation.[1]

Where it came from and why

The review says the compound was made in a search for a monoamine oxidase inhibitor, a goal unrelated to cancer. The 1963 report by Bollag and Grunberg is titled as describing a new class of cytotoxic agents. The sources read do not say how the antitumour activity was noticed.

Cancers

  • Hodgkin lymphoma

    The current US label lists it with other anticancer drugs for Stage III or IV Hodgkin lymphoma. It is the P in MOPP: a 1986 report of 20 years of MOPP followed 198 patients.[1]

  • Anaplastic oligodendroglioma and low-grade glioma (PCV regimen)

    Procarbazine, lomustine and vincristine (PCV) was added to radiotherapy in randomised trials in anaplastic oligodendroglioma (EORTC 26951) and in grade 2 glioma.[7]

  • Glioblastoma at first relapse

    Procarbazine was the comparator for temozolomide in a randomised phase II study of 225 patients with glioblastoma at first relapse.[8]

Worth knowing

  • In a 1986 analysis of MOPP in Hodgkin disease, 157 of 188 patients (84%) achieved a complete response, and 66% of them (101 patients) remained disease-free for more than 10 years after treatment.[9]
  • In the long-term follow-up of EORTC 26951 (368 patients with anaplastic oligodendroglial tumours), median overall survival was 42.3 months with radiotherapy plus PCV and 30.6 months with radiotherapy alone (hazard ratio 0.75; 95% CI 0.60 to 0.95).[7]
  • In long-term results of a randomised trial in grade 2 glioma (251 patients), median overall survival was 13.3 years with radiotherapy plus PCV and 7.8 years with radiotherapy alone (hazard ratio for death 0.59; P = 0.003).[10]
  • A 2004 review says late toxicities, especially secondary leukaemias and sterility, led to the withdrawal of procarbazine from combination regimens for Hodgkin lymphoma, and that it was reintroduced in dose-intensified BEACOPP.[4]
  • A 2007 review says procarbazine was first granted approval in 1965 (the country is not named) and later marketed in around 84 countries. The Drugs@FDA history shows the US original approval on 22 July 1969, and the current US label gives 1969 as the initial US approval.[2]

References

  1. Leadiant Biosciences, Inc. Matulane (procarbazine hydrochloride) capsules: prescribing information. DailyMed, set ID 1aa75a3a-18c9-49e1-91a6-293d0b7da756, published 14 October 2026. Source
  2. Armand JP, Ribrag V, Harrousseau JL, Abrey L. Reappraisal of the use of procarbazine in the treatment of lymphomas and brain tumors. Ther Clin Risk Manag. 2007;3(2):213-24. PubMedDOI
  3. BOLLAG W, GRUNBERG E. Tumour inhibitory effects of a new class of cytotoxic agents: methylhydrazine derivatives. Experientia. 1963;19:130-1. PubMedDOI
  4. Massoud M, Armand JP, Ribrag V. Procarbazine in haematology: an old drug with a new life?. Eur J Cancer. 2004;40(13):1924-7. PubMedDOI
  5. DeVita VT Jr, Lewis BJ, Rozencweig M, Muggia FM. The chemotherapy of Hodgkin's disease: past experiences and future directions. Cancer. 1978;42(2 Suppl):979-90. PubMedDOI
  6. U.S. Food and Drug Administration. Drugs@FDA: Approval date(s) and history, letters, labels, reviews for NDA 016785 (procarbazine hydrochloride; Matulane). Page read 2026-10-26. Source
  7. van den Bent MJ, Brandes AA, Taphoorn MJ, Kros JM, Kouwenhoven MC, Delattre JY, et al. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol. 2013;31(3):344-50. PubMedDOI
  8. Yung WK, Albright RE, Olson J, Fredericks R, Fink K, Prados MD, et al. A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer. 2000;83(5):588-93. PubMedDOI
  9. Longo DL, Young RC, Wesley M, Hubbard SM, Duffey PL, Jaffe ES, et al. Twenty years of MOPP therapy for Hodgkin's disease. J Clin Oncol. 1986;4(9):1295-306. PubMedDOI
  10. Buckner JC, Shaw EG, Pugh SL, Chakravarti A, Gilbert MR, Barger GR, et al. Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma. N Engl J Med. 2016;374(14):1344-55. PubMedDOI