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Other cytotoxics, enzymes and natural productsNever marketedSyntheticNeeds review

Mitoguazone

Also known as MGBG, methyl-GAG, methylglyoxal bis(guanylhydrazone)

A synthetic bis(guanylhydrazone) that inhibits polyamine biosynthesis. Initial clinical trials were stopped in the mid-1960s because of severe side effects; later trials used doses every one to two weeks and included lymphoma. No regulatory approval or marketing was found.

From discovery to approval

  1. 1961 · Earliest report found

    The earliest paper found that names the compound is a 1961 report by Regelson and Holland, titled as an initial clinical study of parenteral methylglyoxal bis(guanylhydrazone) diacetate. A 1962 paper by Freireich, Frei and Karon is titled as describing it as a new agent active against acute myelocytic leukaemia. Neither has an abstract.[2][3][4][5][6]

  2. No approval is recorded on this site.

How it works

A known inhibitor of polyamine biosynthesis, acting through competitive inhibition of S-adenosylmethionine decarboxylase.[1]

Where it came from and why

No source read says why it was made. A 1989 review says initial clinical trials were stopped in the mid-1960s because of severe side effects, and a 1983 review says that after two decades of neglect, doses of 500 to 600 mg/m2 every 7 to 14 days were very well tolerated.

Cancers

  • Acute leukaemia

    The 1962 and 1965 papers are titled as describing activity against acute myelocytic leukaemia and treatment of acute leukaemia (titles only).[3]

  • AIDS-related lymphoma

    A multicentre phase II trial in 35 patients with relapsed or refractory disease: among 26 assessable patients the objective response rate was 23% (95% CI 6.9 to 39.3).[7]

Worth knowing

  • A 1983 review reported useful antitumour activity in advanced malignant lymphoma and carcinomas of the head and neck, oesophagus and lung (non-small cell), and said its cytotoxic mechanism and toxic effects are not shared by most other cancer drugs.[6]
  • In a phase II study of 18 patients with AIDS-related non-Hodgkin lymphoma given low-dose CHOP plus mitoguazone, the response rate was 79% (complete 43%, partial 36%) among 14 evaluable patients; the authors wrote that these preliminary results suggest no major improvement in response over CHOP without mitoguazone.[8]
  • A 1989 minireview mentions psoriasis vulgaris as an additional field of application then expected for the drug.[5]

References

  1. Ferioli ME, Berselli D, Caimi S. Effect of mitoguazone on polyamine oxidase activity in rat liver. Toxicol Appl Pharmacol. 2004;201(2):105-11. PubMedDOI
  2. REGELSON W, HOLLAND JF. Initial clinical study of parenteral methylglyoxal bis(guanylhydrazone) diacetate. Cancer Chemother Rep. 1961;11:81-6. PubMed
  3. FREIREICH EJ, FREI E 3rd, KARON M. Methylglyoxal bis (guanylhydrazone): a new agent active against acute myelocytic leukemia. Cancer Chemother Rep. 1962;16:183-6. PubMed
  4. LEVIN RH, HENDERSON E, KARON M, FREIREICH EJ. TREATMENT OF ACUTE LEUKEMIA WITH METHYLGLYOXAL-BIS-GUANYLHYDRAZONE (METHYL GAG). Clin Pharmacol Ther. 1965;6:31-42. PubMedDOI
  5. Hoffmann H, Gutsche W, Amlacher R, Schulze W, Werner W, Lenk H, et al. [Mitoguazone (methylglyoxal bis(guanylhydrazone))--its status and prospects]. Arch Geschwulstforsch. 1989;59(2):135-48. PubMed
  6. Warrell RP Jr, Burchenal JH. Methylglyoxal-bis(guanylhydrazone) (Methyl-GAG): current status and future prospects. J Clin Oncol. 1983;1(1):52-65. PubMedDOI
  7. Levine AM, Tulpule A, Tessman D, Kaplan L, Giles F, Luskey BD, et al. Mitoguazone therapy in patients with refractory or relapsed AIDS-related lymphoma: results from a multicenter phase II trial. J Clin Oncol. 1997;15(3):1094-103. PubMedDOI
  8. Tulpule A, Espina BM, Pedro Santabarbara AB, Palmer M, Schiflett J, Boswell W, et al. Treatment of AIDS related non-Hodgkin's lymphoma with combination mitoguazone dihydrochloride and low dose CHOP chemotherapy: results of a phase II study. Invest New Drugs. 2004;22(1):63-8. PubMedDOI