Skip to content
Bending the Curve Trial by Trial
?

Other antitumour antibioticsObsoleteNatural productNeeds review

Plicamycin

Also known as Mithramycin, Mithracin

An aureolic acid antibiotic once given by injection for testicular cancer and for hypercalcaemia of malignancy. Drugs@FDA lists its US application, Mithracin, as discontinued.

From discovery to approval

  1. 1960 · Earliest report found

    The earliest papers found are two 1960 clinical reports in Cancer Chemotherapy Reports, on its human toxicology and on its evaluation in solid tumours of adults (titles only). A 2009 review says it is made by Streptomyces argillaceus. The cited papers do not state when or by whom it was isolated.[2][3][1][4][5]

  2. 1970-05-05 · FDA regular

    Plicamycin for injection (Mithracin), Pfizer, NDA 050109, original approval, classed as a new molecular entity (Type 1) with priority review in the Drugs@FDA history, which now lists the product as discontinued. The label is not available there, so the indication at approval is not stated here. LiverTox says plicamycin has not been approved for cancer chemotherapy in the United States; the conflict is not resolved. The type regular is an inference: no accelerated-approval wording was found.[6]

How it works

A 2009 review says it binds G-C-rich DNA sequences and inhibits the binding of transcription factors such as Sp1, and that repeated use can cause kidney, liver and blood toxicity.[1]

Where it came from and why

The papers cited do not state why mithramycin was selected for testing. Its early reports in the 1960s concern disseminated solid tumours and embryonal carcinoma of the testis (titles), and later reports describe its use for hypercalcaemia.

Cancers

  • Testicular cancer

    In a 1995 follow-up, the investigators gave mithramycin to 62 patients with advanced testicular carcinoma as initial chemotherapy between 1963 and 1975: 13 complete regressions (23%) occurred among 56 who received more than one course.[5]

  • Hypercalcaemia of malignancy

    Not a cancer but a complication of cancer. In a randomised crossover trial of 48 patients with tumour-related hypercalcaemia, pamidronate normalised serum calcium more often than plicamycin (88% against 45% of evaluable patients).[7]

Worth knowing

  • In a 1995 follow-up of 13 patients with complete regression of testicular carcinoma, the authors write that a median follow-up of 23 years "implies that these patients are cured"; 85% of the 13 never had a recurrence.[5]
  • In 1992 a randomised crossover trial of 48 patients found pamidronate more effective and better tolerated than plicamycin for tumour-related hypercalcaemia; vomiting occurred in 36% of the evaluable plicamycin patients and in none given pamidronate.[7]
  • LiverTox (updated 2020) says plicamycin has not been approved as cancer chemotherapy in the United States and continues to be used on an investigational basis, whereas Drugs@FDA lists an original approval of Mithracin on 5 May 1970 with no indication shown.[8]

References

  1. Demain AL, Sanchez S. Microbial drug discovery: 80 years of progress. J Antibiot (Tokyo). 2009;62(1):5-16. PubMedDOI
  2. CURRERI AR, ANSFIELD FJ. Mithramycin-human toxicology and preliminary therapeutic investigation. Cancer Chemother Rep. 1960;8:18-22. PubMed
  3. PARKER GW, WILTSIE DS, JACKSON CB Jr. The clinical evaluation of PA-144(mithramycin) in solid tumors of adults. Cancer Chemother Rep. 1960;8:2083-99. PubMed
  4. Kennedy BJ, Griffen WO Jr, Lober P. Specific effect of mithramycin on embryonal carcinoma of the testis. Cancer. 1965;18(12):1631-6. PubMedDOI
  5. Kennedy BJ, Torkelson JL. Long-term follow-up of stage III testicular carcinoma treated with mithramycin (plicamycin). Med Pediatr Oncol. 1995;24(5):327-8. PubMedDOI
  6. U.S. Food and Drug Administration. Drugs@FDA: Approval date(s) and history, letters, labels, reviews for NDA 050109 (Mithracin, plicamycin; Pfizer). Page read 2026-10-29. Source
  7. Thürlimann B, Waldburger R, Senn HJ, Thiébaud D. Plicamycin and pamidronate in symptomatic tumor-related hypercalcemia: a prospective randomized crossover trial. Ann Oncol. 1992;3(8):619-23. PubMedDOI
  8. Plicamycin [no author listed]. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Contribution date 19 February 2020. PubMed 31644044. Source