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Bending the Curve Trial by Trial
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Anthracyclines and anthracenedionesUsed in a few countriesDerivative of an earlier drugNeeds review

Pirarubicin

Also known as THP-adriamycin, Tetrahydropyranyladriamycin, THP

A tetrahydropyranyl derivative of doxorubicin (THP) given by injection. Randomised and phase 2 studies in lymphoma and childhood leukaemia are reported, including by a Japanese study group; the sources read do not say where it is approved.

From discovery to approval

  1. 1982 · Earliest report found

    A 1982 Cancer Research paper by Tsuruo and colleagues called 4'-O-tetrahydropyranyladriamycin (THP-ADM) a new derivative of Adriamycin, equally or more effective against several mouse tumours. A 1979 paper titled 'Tetrahydropyranyl derivatives of daunomycin and adriamycin' has no abstract. A 1987 review says it was designed from the structure of baumycins.[2][3][4][1][5]

  2. No approval is recorded on this site.

How it works

The sources read describe effects, not a molecular mechanism: it inhibited growth of cultured L1210 cells at lower concentrations than doxorubicin did, and a 1987 review says it is rapidly taken up by doxorubicin-sensitive and resistant leukaemic cells.[1]

Where it came from and why

The 1987 review reports that it had stronger effects than adriamycin against mouse L1210 and P388 leukaemia, B16 melanoma and colon 38 adenocarcinoma, with cardiac toxicity as low as that of aclacinomycin.

Cancers

  • Lymphoid malignancies

    In 38 adults with acute lymphoblastic leukaemia or non-Hodgkin lymphoma given 10 mg/m2 for 5 days, 7 complete and 15 partial responses were seen in 35 evaluable patients (overall response rate 62.8%).[6]

  • Diffuse large B-cell lymphoma

    A randomised phase 3 noninferiority trial of 81 patients under 70 compared R-THP-COP with R-CHOP and found a complete response rate of 85% in both groups.[5]

  • Childhood acute lymphoblastic leukaemia

    A Japanese study group trial randomised 276 children with B-ALL to a regimen with pirarubicin (25 mg/m2 x 11) or daunorubicin (30 mg/m2 x 11) and compared toxicities.[7]

Family and partners

Derived from: Doxorubicin

Worth knowing

  • The 1985 mouse study found that 50% growth inhibition of cultured L1210 cells needed 0.003 microgram/ml of THP and 0.016 microgram/ml of doxorubicin.[4]
  • In the childhood leukaemia trial acute haematological toxicity was greater with pirarubicin, while the authors found it appeared less cardiotoxic and gave a comparable event-free survival rate.[7]
  • In the phase 3 lymphoma trial 5-year overall survival was 87% with R-CHOP and 82% with R-THP-COP (hazard ratio 0.89, 95% CI 0.31 to 2.49), with no grade 3 cardiac events in either group.[5]
  • A 2017 cell study in HL-60 leukaemia cells reports that pirarubicin-induced apoptosis involves generation of hydrogen peroxide.[8]

References

  1. Umezawa K, Kunimoto S, Takeuchi T. Experimental studies of new anthracyclines: aclacinomycin, THP-adriamycin and ditrisarubicins. Biomed Pharmacother. 1987;41(5):206-13. PubMed
  2. Umezawa H, Takahashi Y, Kinoshita M, Naganawa H, Masuda T, Ishizuka M, et al. Tetrahydropyranyl derivatives of daunomycin and adriamycin. J Antibiot (Tokyo). 1979;32(10):1082-4. PubMedDOI
  3. Tsuruo T, Iida H, Tsukagoshi S, Sakurai Y. 4'-O-tetrahydropyranyladriamycin as a potential new antitumor agent. Cancer Res. 1982;42(4):1462-7. PubMed
  4. Matsushita Y, Kumagai H, Yoshimoto A, Tone H, Ishikura T, Takeuchi T, et al. Antitumor activities of (2"R)-4'-O-tetrahydropyranyl-adriamycin (THP) and its combination with other antitumor agents on murine tumors. J Antibiot (Tokyo). 1985;38(10):1408-19. PubMedDOI
  5. Hara T, Yoshikawa T, Goto H, Sawada M, Yamada T, Fukuno K, et al. R-THP-COP versus R-CHOP in patients younger than 70 years with untreated diffuse large B cell lymphoma: A randomized, open-label, noninferiority phase 3 trial. Hematol Oncol. 2018;36(4):638-644. PubMedDOI
  6. Takagi T, Oguro M. (2"-R)-4'-o-tetrahydropyranyladriamycin, a new anthracycline derivative; its effectiveness in lymphoid malignancies. Cancer Chemother Pharmacol. 1987;20(2):151-4. PubMedDOI
  7. Hori H, Kudoh T, Nishimura S, Oda M, Yoshida M, Hara J, et al. Acute and late toxicities of pirarubicin in the treatment of childhood acute lymphoblastic leukemia: results from a clinical trial by the Japan Association of Childhood Leukemia Study. Int J Clin Oncol. 2017;22(2):387-396. PubMedDOI
  8. Mizutani H, Hotta S, Nishimoto A, Ikemura K, Miyazawa D, Ikeda Y, et al. Pirarubicin, an Anthracycline Anticancer Agent, Induces Apoptosis Through Generation of Hydrogen Peroxide. Anticancer Res. 2017;37(11):6063-6069. PubMedDOI