Skip to main content
SpringerLink
Log in

Oral Idarubicin in Solid Tumour Chemotherapy

  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Summary

Idarubicin has an established place in the treatment of acute myelogenous leukaemia but is not widely used in the treatment of adult solid tumours. Unlike the anthracyclines now used to treat solid tumours, idarubicin has the advantage of being active after oral administration. In preclinical studies, idarubicin was active against human adenocarcinoma cell lines, including some that were resistant to doxorubicin. This activity was confirmed against human tumour xenografts in vivo.

Oral idarubicin is active against advanced breast cancer. The response rate is 24% and the drug is generally well tolerated. Both 1- and 3-day schedules of administration appear to be equally effective. Response rates are higher when oral idarubicin is given in combination with oral cyclophosphamide (44%). The combination of oral idarubicin with cyclophosphamide and fluorouracil is also tolerated well and has a 53% response rate. Two randomised studies, both small and without quality of life evaluation, compared oral idarubicin with doxorubicin. In the first study, the 2 treatments were equally effective but idarubicin had fewer side effects, while in the second, doxorubicin had a significantly higher response rate than idarubicin. Oral idarubicin has not shown useful activity in the other solid tumours against which it has been tested [small cell lung cancer and non-small cell lung cancer, ovarian, stomach, colorectal and prostatic cancer, melanoma and AIDS-related Kaposi’s sarcoma].

It is likely that idarubicin is less active but also better tolerated than doxorubicin in solid tumours. Oral idarubicin may, therefore, have a place in the palliative treatment of advanced breast cancer. It may be particularly appropriate for elderly patients or those who have difficulty tolerating intravenous treatment. This should be explored further in trials that include quality of life studies. At present, a role for oral idarubicin in the treatment of other solid tumours has not been established. However, alternative schedules of administration and means of controlling the absorption of oral idarubicin are worthy of investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Von Hoff DD. Uses of daunorubicin in patients with solid tumours. Semin Oncol 1984; XISuppl. 3: 23–7

    Google Scholar 

  2. Hayward JL, Carbone PP, Heuson J-C, et al. Assessment of response to therapy in advanced breast cancer. Eur J Cancer 1977; 18: 89–94

    Google Scholar 

  3. WHO handbook for reporting results of cancer treatment. Geneva, WHO Offset Publication no. 48, 1979

  4. Casazza AM. Experimental evaluation of anthracycline analogs. Cancer Treat Rep 1979; 63: 835–44

    PubMed  CAS  Google Scholar 

  5. Salmon SE, Liu RM, Casazza AM. Evaluation of new anthracycline analogs with the human tumor stem cell assay. Cancer Chemother Pharmacol 1981; 6: 103–11

    Article  PubMed  CAS  Google Scholar 

  6. Berens ME, Saito T, Welander CE, et al. Antitumour activity of new anthracycline analogues in combination with interferon alfa. Cancer Chemother Pharmacol 1987; 19: 301–6

    Article  PubMed  CAS  Google Scholar 

  7. Dodion P, Sanders C, Rombaut W, et al. Effect of daunorubicin, carminomycin, idarubicin and 4-demethoxydaunorubicinol against human normal myeloid stem cells and human malignant cells in vitro. Eur J Cancer Clin Oncol 1987; 23: 1909–14

    Article  PubMed  CAS  Google Scholar 

  8. Zijlstra JG, Meijer C, Timmer-Bosscha H, et al. Activity of (7) anthracycline related compounds in an doxorubicin sensitive human small cell lung cancer line and its doxorubicin resistant descendant. Eur J Resp Dis 1987; 70Suppl. 149: 5355

    Google Scholar 

  9. Schott B, Robert J. Comparative cytotoxicity, DNA synthesis inhibition and drug incorporation of eight anthracyclines in a model of doxorubicin-sensitive and -resistant rat glioblastoma cells. Biochem Pharmacol 1989; 38: 167–72

    Article  PubMed  CAS  Google Scholar 

  10. Woods KE, Ellis AL, Randolph JK, et al. Enhanced sensitivity of the rat hepatoma cell to the daunorubicin analogue 4-demethoxydaunorubicin associated with induction of DNA damage. Cancer Res 1989; 49: 4846–51

    PubMed  CAS  Google Scholar 

  11. Gillies HC, Herriott D, Liang R, et al. Pharmacokinetics of idarubicin (4-demethoxydaunorubicin; IMI-30; NSC 256439) following intravenous and oral administration in patients with advanced cancer. Br J Clin Pharmacol 1988; 23: 303–10

    Article  Google Scholar 

  12. Formelli F, Casazza AM, Di Marco A, et al. Fluorescence assay of tissue distribution of 4-demethoxydaunorubicin and 4-demethoxydoxorubicin in mice bearing solid tumours. Cancer Chemother Pharmacol 1979; 3: 261–9

    Article  PubMed  CAS  Google Scholar 

  13. Arcamone F, Bernardi L, Giardino R, et al. Synthesis and antitumor activity of 4-demethoxydaunorubicin, 4-demethoxy-7,9-diepidaunorubicin, and their b anomers. Cancer Treat Rep 1976; 60: 829–34

    PubMed  CAS  Google Scholar 

  14. Di Marco A, Casazza AM, Pratesi G. Antitumour activity of 4demethoxydaunorubicin administered orally. Cancer Treat Rep 1977; 61: 893–4

    PubMed  Google Scholar 

  15. Giuliani FC, Kaplan NO. The use of athymic mice in the screening of new anthracycline derivatives. In Sordat B, editor. Immune-deficient animals. Basel: Karger, 1984: 374–8

    Google Scholar 

  16. Casazza AM, Barbieri B, Fumagalli A, et al. Biologic activity of 4-demethoxy-13-dihydrodaunorubicin (4-dm-130H-DNR). [abstract 991]. Proc Am Assoc Cancer Res 24: 251, 1983

    Google Scholar 

  17. Phillips RM, Bibby MC, Double J. A critical appraisal of the predictive value of in vitro chemosensitivity assays. JNCI 1990; 82: 1457–68

    Article  PubMed  CAS  Google Scholar 

  18. Decoster G, Stein G, Holdener EE. Responses and toxic deaths in Phase I clinical trials. Ann Oncol 1990; 1: 175–81

    PubMed  CAS  Google Scholar 

  19. Marsoni, Hoth D, Simon R, et al. Clinical drug development. An analysis of phase II trial 1970–1985. Cancer Treat Rep 1987; 71: 71–80

    PubMed  CAS  Google Scholar 

  20. Swenerton KD, Legha SS, Smith T, et al. Prognostic factors in metastatic breast cancer treated with combination chemotherapy. Cancer Res 1979; 39: 1552–62

    PubMed  CAS  Google Scholar 

  21. Gregory WM, Smith P, Richards MA, et al. Chemotherapy of advanced breast cancer: outcome and prognostic factors. Br J Cancer 1993; 68: 988–95

    Article  PubMed  CAS  Google Scholar 

  22. Bonfante V, Ferrari L, Brambilla C, et al. New anthracycline analogs in advanced breast cancer. Eur J Cancer Clin Oncol 1986; 22: 1379–85

    Article  PubMed  CAS  Google Scholar 

  23. ten Bokkel Huinink WW, Clavel M, et al. Esorubicin v. idarubicin in advanced breast cancer. A randomized phase II study of the early clinical trials group. Clin Trials J 1987; 24: 143–9

    Google Scholar 

  24. Bastholt L, Dalmark M. Phase II study of idarubicin given orally in the treatment of anthracycline-naive advanced breast cancer patients. Cancer Treat Rep 1987; 71: 451–4

    PubMed  CAS  Google Scholar 

  25. Bastholt L, Dalmark M, Jakobsen A, et al. Weekly oral idarubicin in postmenopausal women with advanced breast cancer. Acta Oncologica 1990; 29: 143–6

    Article  PubMed  CAS  Google Scholar 

  26. Casper ES, Raymond V, Hakes TB, et al. Phase II evaluation of orally administered idarubicin in patients with advanced breast cancer. Cancer Treat Rep 1987; 71: 1289–90

    PubMed  CAS  Google Scholar 

  27. Chevallier B, Monnier A, Metz R, et al. Phase II study of oral idarubicin in elderly patients with advanced breast cancer. Am J Clin Oncol 1990; 13: 436–9

    Article  PubMed  CAS  Google Scholar 

  28. Hurteloup P, Armand JP, Schneider M, et al. Phase II trial of idarubicin (4-demethoxydaunorubicin) in advanced breast cancer. Eur J Cancer Clin Oncol 1989; 25: 423–8

    Article  PubMed  CAS  Google Scholar 

  29. Kolaric K, Mechl Z, Potrebica V, et al. Phase II study of oral 4demethoxydaunorubicin in previously treated (except anthracyclines) metastatic breast cancer patients. Oncology 1987; 44: 82–6

    Article  PubMed  CAS  Google Scholar 

  30. de Lena M, Brandi M, Bozzi D, et al. 4-demethoxydaunorubicin administered orally in advanced breast cancer. A phase II study. Tumori 1988; 74: 65–70

    PubMed  Google Scholar 

  31. Lionetto R, Pronzato P, Conte PF, et al. Idarubicin in advanced breast cancer: a phase II study. Cancer Treat Rep 1986; 70: 1439–43

    PubMed  CAS  Google Scholar 

  32. Lopez M, di Lauro L, Papaldo P, et al. Phase II trial with oral idarubicin in advanced breast cancer. Invest New Drugs 1986; 4: 39–42

    PubMed  CAS  Google Scholar 

  33. Martoni A, Pacciarini MA, Pannuti F. Activity of 4-demethoxydaunorubicin by the oral route in advanced breast cancer. Eur J Cancer Clin Oncol 1985; 21: 803–6

    Article  PubMed  CAS  Google Scholar 

  34. Possinger K, Wagner H, Worst P, et al. Oral administration of idarubicin as first line cytostatic therapy in patients with metastasized breast cancer and favourable prognosis. A trial of the phase II study group of the Association for Medical Oncology of the German Cancer Society. Onkologie 1991; 14: 31–4

    Article  PubMed  CAS  Google Scholar 

  35. Smith DB, Howell A. A phase II study of oral weekly 4-demethoxydaunorubicin in advanced breast cancer. Eur J Cancer Clin Oncol 1987; 23: 391–4

    Article  PubMed  CAS  Google Scholar 

  36. Stuart NSA, Cullen MH, Priestman MH, et al. A phase II study of oral idarubicin (4-demethoxydaunorubicin) in advanced breast cancer. Cancer Chemother Pharmacol 1988; 21: 351–4

    Article  PubMed  CAS  Google Scholar 

  37. Wander H-E, Meyer D, Schuff-Werner P, et al. Phase II trial of oral idarubicin (4-demethoxydaunorubicin) in advanced breast cancer. Onkologie 1986; 9: 236–8

    Article  PubMed  CAS  Google Scholar 

  38. Elbaek K, Ebbehoj E, Jakobsen A, et al. Pharmacokinetics of oral idarubicin in breast cancer patients with reference to antitumor activity and side effects. Clin Pharmacol Ther 1989; 45: 627–34

    Article  PubMed  CAS  Google Scholar 

  39. Kolaric K, Mechl Z. Combination of idarubicin and cyclophosphamide administered orally in untreated postmenopausal breast cancer patients. A phase II study. Oncology 1991; 48: 93–6

    Article  PubMed  CAS  Google Scholar 

  40. Lopez M, Vici P, Carpano S, et al. Combination chemotherapy with oral idarubicin and cyclophosphamide for metastatic breast cancer. J Cancer Res Clin Oncol 1991; 117: 61–4

    Article  PubMed  CAS  Google Scholar 

  41. Kolaric K, Potrebica V, Vukas D, et al. Combination chemotherapy with 5-fluorouracil, oral idarubicin, and cyclophosphamide (FIC) in metastatic breast cancer — an open phase II study. J Cancer Clin Oncol 1988; 114: 301–5

    Article  CAS  Google Scholar 

  42. Smith DB, Howell A. A phase II trial of oral idarubicin plus dimbromodulcitol in advanced breast cancer. Eur J Cancer Clin Oncol 1989; 25: 141–3

    Article  PubMed  CAS  Google Scholar 

  43. Mechl Z, Sopkova B, Nemec J, et al. Idarubicin and dibromodulcitol in the therapy of advanced breast cancer. Int J Exp and Clin Chemother 1989; 2: 47–50

    Google Scholar 

  44. Alberto P. Phase II study of an oral combination of doxifluridine, prednimustine and idarubicin (FUPRIDA) for first-line treatment of advanced breast cancer. Ann Oncol 1993; 4: 423–5

    PubMed  CAS  Google Scholar 

  45. Lopez M, Contegiacomo A, Vici P, et al. A prospective randomized trial of doxorubicin versus idarubicin in the treatment of advanced breast cancer. Cancer 1989; 64: 2431–6

    Article  PubMed  CAS  Google Scholar 

  46. Martoni A, Piana E, Guaraldi M, et al. Comparative phase II study of idarubicin versus doxorubicin in advanced breast cancer. Oncology 1990; 47: 427–32

    Article  PubMed  CAS  Google Scholar 

  47. Kris MG, Gralla RJ, Kelsen DP, et al. Phase II trial of oral 4-demethoxydaunorubicin in patients with non-small cell lung cancer. Am J Clin Oncol (CCT) 1985; 8: 377–9

    Article  CAS  Google Scholar 

  48. Hochster HS, Green MD, Blum RH, et al. Oral 4-demethoxydaunorubicin (idarubicin) in bronchogenic lung cancer; phase II trial. Invest New Drugs 1986; 4: 275–8

    Article  PubMed  CAS  Google Scholar 

  49. Ardizzoni A, Pronzato P, Repetto L, et al. Phase II trial of oral idarubicin advanced non-small cell lung cancer (NSCLC). Cancer Invest 1988; 6: 409–11

    Article  PubMed  CAS  Google Scholar 

  50. Presgrave P, Woods R, Kefford R, et al. A phase II trial of oral 4’demethoxydaunorubicin (DMDR) in inoperable lung cancer. Invest New Drugs 1988; 6: 219–21

    Article  PubMed  CAS  Google Scholar 

  51. Ettinger DS, Finkelstein DM, Doehower RC, et al. Phase II trial of N-methylformamide, spirogermanium, and 4-demethoxydaunorubicin in the treatment of non-small cell lung cancer (EST 3583): an Eastern Cooperative Oncology Group study. Medical and Pediatric Oncology 1989; 17: 197–201

    Article  PubMed  CAS  Google Scholar 

  52. Umsawasdi T, Holoye P, Jeffries D, et al. Phase II trial of idarubicin in extensive disease non-small-cell lung cancer. Am J Clin Oncol (CCT) 1989; 12: 519–20

    Article  CAS  Google Scholar 

  53. Cullen MH, Smith SR, Benfield GFA, et al. Testing new drugs in untreated small cell lung cancer may prejudice the results of standard treatment: a phase II study of oral idarubicin in extensive disease. Cancer Treat Rep 1987; 71: 1227–30

    PubMed  CAS  Google Scholar 

  54. Milroy R, Cummings J, Kaye SB, et al. Phase II clinical and pharmacological study of oral 4-demethoxydaunorubicin in advanced non-pretreated small cell lung cancer. Cancer Chemother Pharmacol 1987; 20: 75–7

    Article  PubMed  CAS  Google Scholar 

  55. Ardizzoni A, Pennucci C, Fusco V, et al. Oral chemotherapy for poor risk small-cell lung cancer patients with combined idarubicin and etoposide. Anticancer Res 1989; 9: 937–40

    PubMed  CAS  Google Scholar 

  56. Abad-Esteve A, Diaz-Rubio E, Jimeno JM, et al. Oral idarubicin for measurable gastric cancer. Am J Clin Oncol 1989; 12: 14–6

    Article  PubMed  CAS  Google Scholar 

  57. Presgrave P, Woods R, Dalley D, et al. A phase II trial of oral 4’demethoxydaunorubicin in advanced colorectal cancer. Am J Clin Oncol 1988; 11: 564–5

    Article  PubMed  CAS  Google Scholar 

  58. Kavanagh JJ, Larry MD, Copeland LT, et al. A phase II trial of 4-demethoxydaunorubicin in refractory epithelial ovarian cancer. Gynaecolog Oncol 1986; 24: 23–6

    Article  CAS  Google Scholar 

  59. Williams CJ. A phase II study of oral idarubicin in advanced recurrent or refractory ovarian carcinoma. Cancer Chemother Pharmacol 1990; 25: 304–5

    Article  PubMed  CAS  Google Scholar 

  60. Madsen EL, Bastolt L, Bertelsen K, et al. Weekly idarubicin in advanced prostatic cancer. A phase II study. Acta Oncol 1992; 31: 337–40

    Article  PubMed  CAS  Google Scholar 

  61. Martoni A, Pacciarini MA, Pannuti F. The new anthracycline 4demethoxydaunorubicin by oral route in advanced pretreated breast cancer and melanoma. A pilot study. Drugs Exp Clin Res 1985; 11: 127–31

    PubMed  CAS  Google Scholar 

  62. Lopez M, di Lauro L, Papaldo P. Phase II evaluation of oral idarubicin (4-demethoxydaunorubicin) in patients with disseminated malignant melanoma. Cancer Treat Rep 1986; 70: 911–2

    PubMed  CAS  Google Scholar 

  63. Chachoua A, Green M, Laubenstein L, et al. Phase II study of oral idarubicin in patients with AIDS-associated Kaposi’s sarcoma. Cancer Treat Rep 1987; 71: 775–6

    PubMed  CAS  Google Scholar 

  64. O’Connell J, Kris M, Gralla R, et al. Frequency and prognostic importance of pretreatment clinical characteristics in patients with advanced non-small cell lung cancer treated with combination chemotherapy. J Clin Oncol 1986; 4: 1604–14

    PubMed  Google Scholar 

  65. Slevin ML, Clark PI, Joel S, et al. A randomized trial to evaluate the effect of schedule on the activity of etoposide in small-cell lung cancer. J Clin Oncol 1989; 7: 1333–40

    PubMed  CAS  Google Scholar 

  66. Issell BF, Einhorn LH, Comis RL, et al. Multicenter phase II trial of etoposide in previously treated small cell carcinoma of the lung. Cancer Treat Rep 1985; 69: 127–8

    PubMed  CAS  Google Scholar 

  67. Souhami RL, Bradbury I, Geddes DM, et al. Prognostic significance of laboratory parameters measured at diagnosis in small cell lung cancer. Cancer Res 1985; 45: 2878–82

    PubMed  CAS  Google Scholar 

  68. Joss RA, Obrecht J-P, Alberto P, et al. Phase II trial of 4-demethoxydaunorubicin in patients with non-small cell lung cancer. Cancer Treat Rep 1984; 68: 563–4

    PubMed  CAS  Google Scholar 

  69. Ozols RF, Young RC. Chemotherapy of advanced ovarian cancer. Semin Oncol 1984; 11: 251–63

    PubMed  CAS  Google Scholar 

  70. Hubbard SM, Barkes P, Young RC. Adriamycin therapy for advanced ovarian carcinoma recurrent after chemotherapy. Cancer Treat Rep 1978; 62: 1375–7

    PubMed  CAS  Google Scholar 

  71. Thigpen JT, Buchsbaum HJ, Mangan C, et al. Phase II trial of adriamycin in the treatment of advanced or recurrent endometrial carcinoma. Cancer Treat Rep 1979; 63: 21–7

    PubMed  CAS  Google Scholar 

  72. Hakes TB, Daghestani AN, Dougherty JB, et al. Phase II study of 4-demethoxydaunorubicin in advanced ovarian carcinoma. Cancer Treat Rev 1985; 69: 559–60

    CAS  Google Scholar 

  73. Seymour MT, Mansi JC, Gallagher CJ, et al. Protracted oral etoposide in epithelial ovarian cancer: a phase II study in patients with relapsed or platinum resistant disease. Br J Cancer 1994; 69: 191–5

    Article  PubMed  CAS  Google Scholar 

  74. McGuire WP, Rowinski FK, Rosenheim NB, et al. Taxol: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann Intern Med 1989; 111: 273–9

    PubMed  CAS  Google Scholar 

  75. Hakes TB, Raymond V. Phase II study of idarubicin in advanced endometrial carcinoma. Cancer Treat Rep 1987; 71: 535–6

    PubMed  CAS  Google Scholar 

  76. Hakes TB, Dougherty JB, Raymond V. Phase II study of idarubicin in advanced cervical carcinoma. Am J Clin Oncol 1986; 9: 262–3

    Article  PubMed  CAS  Google Scholar 

  77. Moertel CG, Lavin PT. Phase II–III chemotherapy studies in advanced gastric cancer. Cancer Treat Rep 1979; 63: 1863

    PubMed  CAS  Google Scholar 

  78. Gastrointestinal Tumor Study Group. Phase II–III chemotherapy studies in advanced gastric cancer. Cancer Treat Rep 1979; 63: 1871

    Google Scholar 

  79. Einzig A, Kelsen D, Cheng E, et al. Phase II study of 4-demethoxydaunorubicin in patients with adenocarcinoma of the upper gastrointestinal tract. Cancer Treat Rep 1984; 68: 1415–6

    PubMed  CAS  Google Scholar 

  80. MacCormick R, Hirsch G, Gupta S, et al. A phase II study of idarubicin in the treatment of measurable gastric cancer. Cancer 1991; 67: 2988–9

    Article  PubMed  CAS  Google Scholar 

  81. Mittelman A, Magill GB, Raymond V, et al. Phase II trial of idarubicin in patients with pancreatic cancer. Cancer Treat Rep 1987; 71: 657–8

    PubMed  CAS  Google Scholar 

  82. Harper HD, Kemeny NE, Ahmed T, et al. Phase II trial of 4-demethoxydaunorubicin in advanced colorectal carcinoma. Cancer Treat Rep 1984; 68: 689–90

    PubMed  CAS  Google Scholar 

  83. Eisenberger MA, Simon R, O’Dwyer PJ, et al. A reevaluation of nonhormonal chemotherapy in the treatment of prostatic carcinoma. J Clin Oncol 1985; 3: 827–41

    PubMed  CAS  Google Scholar 

  84. Yagoda A. Chemotherapy of renal cell carcinoma. Semin Urol 1989; 7: 199–206

    PubMed  CAS  Google Scholar 

  85. Borden EC, Amato DA, Rosenbaum C, et al. Randomized comparison of three adriamycin regimens for metastatic soft tissue sarcomas. J Clin Oncol 1987; 5: 840–50

    PubMed  CAS  Google Scholar 

  86. Stanton G, Casper ES, Friedman B. Phase II trial of 4-demethoxydaunorubicin in patients with advanced malignant melanoma. Cancer Treat Rep 1985; 69: 915–6

    PubMed  CAS  Google Scholar 

  87. Scher HI, Yagoda A, Ahmed T, et al. Phase-II trial of 4-demethoxydaunorubicin (DMDR) for advanced hypernephroma. Cancer Chemother Pharmacol 1985; 14: 79–80

    Article  PubMed  CAS  Google Scholar 

  88. Dobbs NA, Twelves CJ, Ramirez A, et al. Patient acceptability and practical implications of pharmacokinetic studies in patients with advanced cancer. Eur J Cancer 1993; 29A: 1707–11

    Article  PubMed  CAS  Google Scholar 

  89. Kaye SB. P glycoprotein (P-gp) and drug resistance — time for reappraisal? Br J Cancer 1993; 67: 641–3

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. CRC Department of Medical Oncology, Alexander Stone Building, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland

    Christopher J. Twelves

Authors
  1. Christopher J. Twelves
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Twelves, C.J. Oral Idarubicin in Solid Tumour Chemotherapy. Clin. Drug Invest. 9 (Suppl 2), 39–54 (1995). https://doi.org/10.2165/00044011-199500092-00007

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00044011-199500092-00007

Keywords

Search

Navigation