Advertisement

Cancer Chemotherapy and Pharmacology

, Volume 35, Issue 2, pp 174–178 | Cite as

A phase I/II study of 4′-O-tetrahydropyranyl-doxorubicin, 5-fluorouracil, and high-dose leucovorin as first-line therapy in advanced breast cancer patients

  • Herbert Stöger
  • Thomas Bauernhofer
  • Marianne Schmid
  • Ferdinand Ploner
  • Renate Moser
  • Elke Derstvenscheg
  • Peter Steindorfer
  • Martini Wilders-Truschnig
  • Iris Kuss
  • Hellmut Samonigg
Clinical Trial Report Breast Cancer, 4′-O-Tetrahydropyranyl-Doxorubicin, Fluorouracil/Leucovorin, Weekly Schedule

Abstract

A total of 50 patients were treated weekly with 5-fluorouracil (FU), leucovorin (LV), and 4′-O-tetrahydropyranyl-doxorubicin (THP) as first-line chemotherapy for advanced breast cancer (ABC). In phase I the doses of LV (500 mg/m2, day 1) and FU (350 mg/m2, day 1) were held constant, while the dose of THP (day 1) was escalated, from the initial dose of 10 mg/m2 up to the maximum tolerated dose (MTD). Twenty-eight patients entered phase I, and MTD for THP was defined as 35 mg/m2 in this combination. Dose-limiting toxicities were myelosuppression and hepatotoxicity. In phase II, another 22 patients were treated with THP at a dose level of 30 mg/m2. Including 4 patients already treated at this dose in the first part, 25 patients were evaluable for response: 1 patient obtained a complete response (CR) and 13 showed a partial response (PR), giving an objective response rate of 56%. The median duration of response was 9.1+ months and median survival, 15.5+ months. Side effects were generally mild, with ECOG grade I and II leukopenia in 51% of all cycles and grade III in 3% of the courses. Other toxicity included nausea and vomiting (54% and 8%, respectively) and alopecia (24%), all restricted to ECOG grade I and II. Our results suggest that weekly THP/LV-FU represents an active regimen for first-line treatment of ABC with relative low toxicity.

Key words

Breast cancer 4′-O-Tetrahydropyranyl-doxorubicin Fluorouracil/Leucovorin Weekly schedule 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Allegra JC, Sholar PW, Drake JC, Bagley C, Lippman ME, Chabner BA (1986) A phase II trial for the treatment of metastatic breast cancer with 5-fluorouracil and leucovorin (abstract). Proceedings of the Symposium on Development of Folates and Folic Acid Antagonists in Cancer Chemotherapy. Innisbrook, Tarpon Springs, p 5Google Scholar
  2. 2.
    Bonnadonna G, Valagussa P (1983) Chemotherapy of breast cancer. Current views and results. Int J Radiat Oncol Biol Phys 9: 279–297Google Scholar
  3. 3.
    Carter SK (1975) Adriamycin, a review. J Natl Cancer Inst 35: 1265Google Scholar
  4. 4.
    Dantchev D, Bourut C, Maral R, Mathé G (1983) Cardiotoxicity and alopecia of 12 different anthracyclines in the golden hamster model. Proceedings of the 13th International Congress of Chemotherapy. Spitzy, Karrer, Vienna, pp 15–19Google Scholar
  5. 5.
    Fujita H (1984) Chemical modification of anticancer agents from the viewpoint of their pharmacokinetics. Gan to Kagaku Ryoho 11: 733–740Google Scholar
  6. 6.
    Hayward JL, Carbone PP, Heuson JC, Kumaoka S, Segaloff A, Rubens RD (1977) Assessment of response to therapy in advanced breast cancer. Cancer 39: 1289Google Scholar
  7. 7.
    Hellman S, Harris J, Canellos GP, et al (1982) Cancer of the breast. In: De Vita V, Hellman S, Rosenberg S (eds) Cancer, principles and practice of oncology. Lippincott, Philadelphia, pp 914–970Google Scholar
  8. 8.
    Henderson IC, Cancellos GP (1980) Cancer of the breast — the past decade. N Engl J Med 302: 17–30; 78–90Google Scholar
  9. 9.
    Henderson IC, Hayes DF, Come S, et al (1987) New agents and new medical treatments for advanced breast cancer. Semin Oncol 14: 34–64Google Scholar
  10. 10.
    Hoogstraten B, Fabian C (1979) A reappraisal of single drugs in advanced breast cancer. Cancer Clin Trials 2: 101–109Google Scholar
  11. 11.
    Kimura K (1986) A phase II study of (2″R)-4′-O-tetrahydropyranyl-adriamycin (THP) in patients with hematological malignancies. Jpn J Cancer Chemother 3: 368–375Google Scholar
  12. 12.
    Machover D, Goldschmidt E, Chollet P et al (1986) Treatment of advanced colorectal and gastric carcinoma with 5-fluorouracil and high-dose folinic acid. J Clin Oncol 4: 685–696Google Scholar
  13. 13.
    Majima H, Iguchi H, Tone H (1986) Pharmacokinetics studies on THP-ADM (Tetrahydropyranyl-adriamycin). Jpn J Cancer Chemother 13: 542–548Google Scholar
  14. 14.
    Marini G, Marcipati P, Zaniboni A, Cervi GC, Gorni F, Simoncini E (1985) Treatment of advanced breast cancer with 5-fluorouracil and high dose folinic acid: preliminary results. Chemiotherapia 4: 135–138Google Scholar
  15. 15.
    Miller AB, Scheulen ME, Kleeberg UR, et al (1988) Phase I study of pirarubicin. J Cancer Res Clin Oncol 114: 91–94Google Scholar
  16. 16.
    Petrelli N, Herrera L, Rustum YM, et al (1987) A prospective randomized trial of 5-fluorouracil versus 5-fluorouracil and highdose leucovorin versus 5-fluorouracil and methotrexate in previously untreated patients with advanced colorectal carcinoma. J Clin Oncol 5: 1559–1565Google Scholar
  17. 17.
    Saito T, Kasai Y, Wakui A, et al (1986) Phase II study of (2″R)-4′-O-tetrahydropyranyladriamycin. Jpn J Cancer Chemother 13: 1060–1069Google Scholar
  18. 18.
    Samonigg H, Kasparek AK, Stoger H, et al (1990) 4′-O-Tetrahydropyranyl-doxorubicin in advanced breast cancer: a phase II study. Cancer Chemother Pharmacol 26: 293–296Google Scholar
  19. 19.
    Scheithauer W, Samonigg H, Depisch D, et al (1989) Pirarubicin (4′-O-tetrahydropyranyl-doxorubicin) for treatment of metastatic breast cancer. Contrib Oncol 37: 89–93Google Scholar
  20. 20.
    Swain SM, Lippman ME, Eagan EF, Drake JC, Steinberg SM, Allegra CJ (1989) Fluorouracil and high-dose leucovorin in previously treated patients with metastatic breast cancer. J Cin Oncol 7: 890–899Google Scholar
  21. 21.
    Tormey DC (1975) Adriamycin (NSC-123127) in breast cancer: an overview of studies. Cancer Chemother Rep 6: 319–327Google Scholar
  22. 22.
    Tormey DC, Gelman R, Band PR, Sears M, Rosenthal SN, Dewys W, Perlia C, Rice MA (1982) Comparison of induction chemotherapies for metastatic breast cancer. Cancer 50: 1235–1244Google Scholar
  23. 23.
    Umezawa H, Takahashi Y, Kinoshita M et al (1979) Tetrahydropyranyl derivates of daunomycin and adriamycin. J Antibiot (Tokyo) 10: 1082–1084Google Scholar
  24. 24.
    Von Hoff DD, Layard MW, Basa P, et al (1979) Risk factors for doxorubicin induced congestive heart failure. Ann Intern Med 91: 710–717Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Herbert Stöger
    • 1
  • Thomas Bauernhofer
    • 1
  • Marianne Schmid
    • 1
  • Ferdinand Ploner
    • 1
  • Renate Moser
    • 1
  • Elke Derstvenscheg
    • 1
  • Peter Steindorfer
    • 2
  • Martini Wilders-Truschnig
    • 1
  • Iris Kuss
    • 1
  • Hellmut Samonigg
    • 1
  1. 1.Department of Internal Medicine, Division of OncologyKarl Franzens University GrazGrazAustria
  2. 2.Department of SurgeryKarl Franzens University GrazGrazAustria

Personalised recommendations