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Phase II trial of pirarubicin in the treatment of advanced bladder cancer

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Summary

Doxorubicin is one of the standard drugs in the chemotherapy of advanced urothelial tumors. Pirarubicin, a new anthracycline, turned out to be equally active and less toxic than its parent compound in preclinical studies. Twenty one patients with either metastatic or inoperable locally advanced bladder carcinoma were treated with intravenous infusion of pirarubicin: 25 mg/m2/day for 3 days every 4 weeks in the first 15 patients and 20 mg/m2/day for 3 days every 3 weeks in the others. Fifteen patients were not pretreated and 6 received prior chemotherapy (5 patients with doxorubicin containing regimen). Twenty patients were evaluable for response; there were 2 partial response, 8 stable disease and 10 progressive disease. All pretreated patients progressed. Hematological toxicity was moderate, however there was one toxic death with grade 4 neutropenia which occured in a heavily pretreated patient receiving a dose of 25 mg/m2/day for 3 days. There was no clinical cardiac toxicity. Single agent Pirarubicin displays an objective response rate of 10% (95% of CI 0 to 23%) which reaches 14% (95% CI 0 to 29%) when non pretreated patients are analyzed separately. This rate is in the range of doxorubicin activity.

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References

  1. Yagoda A: Chemotherapy of urothelial tract tumors. Cancer 60:574–585, 1987

    Google Scholar 

  2. Sternberg CN, Yagoda A, Scher HI, Watson RC, Geller NL, Herr HW, Morse MJ, Sagoni PC, Vaughan ED, Bander N, Weiselberg L, Rosado K, Smart T, Shiow-Yun L, Penenberg D, Fair WR, Whitmore WF: Methotrexate, Vinblastine, Doxorubicin and Cisplatin for advanced transitional cell carcinoma of the urothelium. Cancer 64:2448–2458, 1989

    Google Scholar 

  3. Geller NL, Sternberg CN, Penenberg DL, Scher HI, Yagoda A: Prognostic factors for survival of patients with advanced urothelial tumors treated with Methotrexate, Vinblastin, Doxorubicin and Cisplatin chemotherapy. Cancer 67:1525–1531, 1991

    Google Scholar 

  4. Boutan-Laroze A, Mahjoubi M, Droz JP, Charrot P, Farget P, Kerbrat P, Caty A, Voisin PM, Spielmann M, Rey A, Giraud B: M-VAC (Methotrexate, Vinblastin, Doxorubicin and Cisplatin) for advanced carcinoma of the bladder. Eur J Cancer 27:1690–1694, 1991

    Google Scholar 

  5. Tsurno T, Iida H, Tsukagoshi S, Sakurai Y: 4′-0-Tetra-hydropyramyladriamycin as a potential new antitumor agent. Cancer research 42:1462–1467, 1982

    Google Scholar 

  6. Majima H: Phase I studies of (2″R)-4′-0-Tetrahyro-pyramyladriamycin (THP) in Japan. In: Advances in experimental and clinical chemotherapy. 15th ICC, Turkey, 1987, pp 31–34

  7. Sridhar KS, Samy TS, Koch G, Agarwal P, Duncan RC, Ganz W, Benedetto P, Feun L, Savaraj N, Gross J, Krishan A, Zubrod CG: Phase I study of 4′-0-Tetrahydropyramyladriamycin. In: Advances in experimental and clinical chemotherapy. 15th ICC, Turkey, 1987, pp 11–26

  8. Okuma K, Furuta I, Ota K: Acute cardiotoxicity of anthracyclines — analysis by using Holter EKG. JPN J cancer chemother 11:901–911, 1984

    Google Scholar 

  9. Herait P, Poutignat N, Schneider M, Brienza S, Misset JL, Mathe G, Armand JP: cardiac tolerance of 4′-0-Tetrahydropyramyladriamycin (THP-ADM, 1609 RB) updated results. Invest New Drugs 7:394, 1989

    Google Scholar 

  10. Miller AB, Hoogstraten B, Staquet M, Winder A: Reporting results of cancer treatment. Cancer 47:207–214, 1981

    Google Scholar 

  11. Alexander J, Dainiak N, Berger HJ: Serial assessment of Doxorubicin cardiotoxicity with quantitative radionuclide angiocardiography. N Engl J Med 300:278–283, 1979

    Google Scholar 

  12. Kaplan E, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481, 1958

    Google Scholar 

  13. Fossa SD, Splinter T, Roozendaal KJ: A phase II study of 4′-0-epiadriamycin in advanced urothelial transitional cell cancer — EORTC — GU protocol. In: Robustelli della cuna, Banadonna G (eds), advances in clinical oncology. Edimes. Italy, 1989, pp 107–118

    Google Scholar 

  14. Gagliano R, Levin H, Elbolkainy MN: Adriamycin Versus adriamycin plus cisdichlorodiaminoplatinum (II) in advanced transitional cell bladder carcinoma. A southwest oncology group study. Am J Clin Oncol 6:215–218, 1983

    Google Scholar 

  15. Niijima T: Phase II collaborative study of (2″R) 4′-0-Tetrahydropyramyladriamycin (THP) for urological malignancies: urological cooperative study group of THP-ADM. JPn J Cancer chemother 13:224–231, 1986

    Google Scholar 

  16. Akaza H, Kotake T, Niijima T, Aso Y, and the Clinical Study Group of THP for Urological Malignant Tumors. Cooperative study of Pirarubicin against urological cancers and future direction of its combination use. Am J Clin Oncol 13 (supp 1):11–14, 1990

    Google Scholar 

  17. O'Bryan R, Baker L, Gottlieb J, Rivkin S, Balcerzak S, Grumet G, Salmon S, Moon T, Hoogstraten B: Dose response evaluation of adriamycin in human neoplasia. Cancer 39:1940–1948, 1977

    Google Scholar 

  18. Logothetis C, Dexeus F, Sella A: Escalated (ESC) M-VAC (MTX 30 mg/m2, Adriamycin 60 mg/m2, Vinblastin 4 mg/m2, Cisplatin 100 mg/m2) with recombinant human granulocytes macrophage colony stimulating factor ((rh GM-CSF) schering corp.) for patients (pts) with advanced and chemotherapy (CHT) refractory urothelium tumors. A phase I study. J Clin Oncol 8:1050–1055, 1990

    Google Scholar 

  19. Miller A, Schmidt C: Clinical pharmacology and toxicity of 4′-0-Tetrahydropyramyladriamycin. Cancer Res 47:1461–1465, 1987

    Google Scholar 

  20. Munck JN, Timus M, Bennoun M, Tapiero H: Plasma and cellular levels of adriamycin and 4′-0-Tetrahydropyramyladriamycin in human. In: progress in cancer chemo-immunotheraépy, Fr-Jpn conf antibiotics in tumor pharmacol. Paris, 1983, pp 55–58

  21. Rougier P, Munck JN, Elias D, Herait P, Bognel C, Gosse C, Lasser E: Intraarterial hepatic chemotherapy with Pirarubicin: Preclinical and clinical studies. Am J Clin Oncol 13:81–84(1990)

    Google Scholar 

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Mahjoubi, M., Kattan, J., Ghosn, M. et al. Phase II trial of pirarubicin in the treatment of advanced bladder cancer. Invest New Drugs 10, 317–321 (1992). https://doi.org/10.1007/BF00944188

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