Skip to main content

Advertisement

SpringerLink
Log in

Oral Idarubicin

A Review of its Pharmacological Properties and Clinical Efficacy in the Treatment of Haematological Malignancies and Advanced Breast Cancer

  • Adis Drug Evaluation
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Synopsis

Idarubicin is an anthracycline agent available as both oral and intravenous formulations. The oral formulation has demonstrated efficacy in the treatment of advanced breast cancer, low-grade non-Hodgkin’s lymphoma, myelodysplastic syndromes and as first-line induction therapy of acute myelogenous leukaemia where intravenous anthracycline treatment is precluded. It also has potential in ameliorating blast crisis of chronic myelogenous leukaemia and in multiple myeloma.

The most frequent adverse effects associated with oral idarubicin are those commonly found with anthracyclines, namely myelosuppression, nausea and vomiting, diarrhoea and mucositis. There appears to be minimal significant cardiotoxicity with oral idarubicin.

In summary, available data concerning oral idarubicin in haematological malignancies and advanced breast cancer are sufficiently encouraging to warrant further research. To maximise the use of oral idarubicin, future studies should define the optimal dose for elderly patients, its comparative efficacy with other available regimens and address quality-of-life and pharmacoeconomic issues associated with the substitution of oral for intravenous chemotherapy.

Pharmacodynamic Properties

Idarubicin is an analogue of daunorubicin, with greater lipophilicity and consequent improved absorption across the gastrointestinal mucosa and enhanced uptake into tumour cells. The major metabolite of idarubicin, idarubicinol, is pharmacologically active, with similar activity in vitro and in vivo to the parent compound. In murine experimental tumour systems, oral idarubicin produced equivalent activity to the intravenous formulation at an approximately 4-fold higher dose. In vivo cytotoxic activity was 4 to 8 times greater than that of either daunorubicin or doxorubicin in models of leukaemias and lymphomas.

The putative mechanism of cytotoxic activity of idarubicin is through interference with DNA synthesis, by means of intercalation between the DNA bases and inhibition of DNA topoisomerase II.

Animal studies indicate that intravenous idarubicin has less cardiotoxic potential than other anthracyclines, with oral administration further reducing cardiotoxicity.

The in vitro activity of idarubicin and idarubicinol is less affected than that of other anthracyclines in multidrug resistant human cancer and leukaemia cell lines compared with sensitive cells.

Pharmacokinetic Properties

Idarubicin is rapidly absorbed after oral administration, with drug concentrations detectable in plasma within 30 minutes. Peak plasma concentrations are observed after between 1 and 9 hours. The proportion of metabolite present in plasma relative to the parent drug is markedly greater after oral than after intravenous administration, reflecting first-pass hepatic metabolism.

Idarubicin and its metabolite are both extensively plasma protein bound, and the drug also undergoes extensive tissue uptake, reflected in a large apparent volume of distribution (1214 to 1889 L/m2).

The principal metabolite, idarubicinol, is formed by reduction of the ketone on carbon 13 in a reaction common to anthracyclines. Rapid transformation to idarubicinol probably accounts for the high total plasma clearance of idarubicin. The plasma elimination half-life (t½) of idarubicin after oral administration is 5 to 24 hours, and that for idarubicinol is between 13 and 60 hours.

Biliary excretion is the primary route of elimination of idarubicin, as for other anthracyclines, but the relative contribution of this route to idarubicin excretion remains to be determined. Urinary excretion is only a minor route of idarubicin, in common with other anthracyclines.

The bioavailability of idarubicin is independent of age, and it is unlikely that the pharmacokinetics of idarubicin are altered in elderly patients. Total plasma clearance is significantly reduced in patients with impaired renal function (creatinine clearance <60 ml/min); in addition, the terminal phase t½ of idarubicinol was prolonged.

Clinical Efficacy

Haematological Malignancies: Oral idarubicin has shown particular efficacy in some haematological malignancies. In noncomparative studies of oral idarubicin as induction monotherapy of acute myelogenous leukaemia (AML) in elderly patients, rates of complete response were between 5 and 40%, with overall or objective (complete plus partial response) responses observed in 10 to 80% of patients. When oral idarubicin was administered as induction therapy in combination with subcutaneous cytarabine, complete response rates were between 41 and 54%, with overall response rates of 47 to 62%. An attenuated- or low-dose oral regimen of idarubicin, etoposide and thioguanine also compared favourably with an oral/intravenous regimen of cytarabine, daunorubicin and thioguanine in terms of both response rates and survival.

The use of oral idarubicin monotherapy in the treatment of myelodysplastic syndromes in elderly patients appears warranted, although further investigation to determine optimal dosage regimens may be necessary. Oral idarubicin was also effective in a small trial of palliative therapy in patients with chronic myelogenous leukaemia in blast crisis, in whom quality of life is an important treatment outcome.

Although treatment-related adverse effects have at times led to somewhat equivocal results with oral idarubicin in patients with multiple myeloma, substantial overall response rates (58 to 66%) observed with oral combination therapy incorporating idarubicin merit further research.

Significant activity of oral idarubicin is apparent from trials in non-Hodgkin’s lymphoma, particularly in patients without prior therapy and with favourable (low-grade) histology. Overall responses to monotherapy ranged from 26 to 65%, with a median response duration of about 6 months. Combination regimens have also proved effective, but their risk-benefit profile in elderly patients remains to be fully established.

Advanced Breast Cancer: In early noncomparative trials, oral idarubicin monotherapy produced overall objective response rates ranging between 13 and 36% in patients with advanced breast cancer. The highest rate of complete response achieved was 11 % in a trial in chemotherapy-naive patients aged between 70 and 84 years. Most patients received intermittent regimens.

In trials comparing oral idarubicin 45 mg/m2/day with intravenous doxorubicin 75 mg/m2/day, differing results have been obtained: in one trial overall objective response rates were 30% with idarubicin and 32% with doxorubicin, with a similar duration of response and survival. However, a second study observed an overall response of 21% with idarubicin versus 46% with doxorubicin. Median response durations were similar, but median survival was 14 months with idarubicin and 20 months with doxorubicin.

Oral idarubicin in combination with cyclophosphamide has produced overall response rates of between 22 and 49%. The median duration of response in these trials was about 7 months. A 3-drug regimen combining oral idarubicin with cyclophosphamide and fluorouracil has also proven effective with a response rate of 53% reported.

Tolerability

Idarubicin appears to produce less cardiotoxicity than other anthracyclines, with clinically significant alterations in cardiac function observed infrequently.

Most patients treated with idarubicin experience myelosuppression, the severity of which is dose dependent. A review of 1399 patients treated with oral idarubicin for solid tumours evinced an incidence of deaths attributable to drug-related toxicity of 1%, although haemopoietic growth factors were not used in any patient. Haematological parameters appear to normalise in most patients after 3 to 4 week’ therapy.

Gastrointestinal adverse events occur frequently and may be more pronounced after oral idarubicin than after an equivalent intravenous dose. The most common events are nausea and vomiting occurring in up to 25 to 86% of patients. Diarrhoea develops in about 10 to 38% of patients receiving oral idarubicin, with mucositis apparent in about 9%. Alopecia occurred in about 35% of patients with solid tumours receiving oral idarubicin 40 to 45 mg/m2 per cycle, but was of moderate severity.

Dosage and Administration

For remission induction in patients with AML for whom intravenous therapy is unsuitable, oral idarubicin is effective at a dosage of 30 mg/m2 daily as mono-therapy or 15 to 30 mg/m2 daily for 3 days in combination regimens. In myelodysplastic syndromes, oral idarubicin 50 mg/m2 in 4 divided doses every 2 to 4 weeks or as a single 50mg dose every 3 to 4 weeks have been effective in elderly patients. In patients with non-Hodgkin’s lymphoma, effective doses ranged from 30 to 45 mg/m2 administered every 3 weeks.

In the treatment of advanced breast cancer, oral idarubicin at a dosage of about 45 mg/m2 every 3 or 4 weeks provides effective monotherapy for patients in whom the disease is refractory to first-line non-anthracycline chemotherapy.

Cardiotoxicity appears unlikely with cumulative oral doses up to 400 mg/m2. Cardiac, renal and hepatic function should be monitored during therapy, and regular peripheral blood counts taken. Dosage reduction may be necessary when bilirubin or creatinine levels are markedly increased.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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. Arcamone F, Bernardi I, Giardino P, et al. Synthesis and antitu-mor activity of 5-demethoxydaunorubicin, 4-demethoxy-7,9-diepidaunorubicin, and their anomers. Cancer Treat Res 1976; 60: 829–32

    CAS  Google Scholar 

  2. Hollingshead LM, Faulds D. Idarubicin: a review of its phar-macodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer. Drugs 1991 Oct; 42: 690–719

    PubMed  CAS  Google Scholar 

  3. Fields SM, Koeller JM. Idarubicin: a second-generation anthra-cycline. Drug Intell Clin Pharm 1991 May; 25: 505–17

    CAS  Google Scholar 

  4. Supino R, Necco A, Dasdia T, et al. Relationship between effects on nucleic acid synthesis in cell cultures and cytotoxicity of 4-demethoxy derivatives of daunorubicin and adriamycin. Cancer Res 1977; 37: 4523–8

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  6. Salmon SE, Liu RM, Casazza AM. Evaluation of new anthracycline analogs with the human tumor stem cell assay. Cancer Chemother Pharmacol 1981; 6: 103–10

    PubMed  CAS  Google Scholar 

  7. Hargrave RM, Davey MW, Davey RA, et al. Development of drug resistance is reduced with idarubicin relative to other anthracyclines. Anticancer Drugs 1995 Jun; 6: 432–7

    PubMed  CAS  Google Scholar 

  8. Minderman H, Buscaglia MD, Rustum YM. Schedule-dependent efficacy of idarubicin (Ida) and doxorubicin (dox). Leukemia 1994 Aug; 8: 1401–5

    PubMed  CAS  Google Scholar 

  9. Ames MM, Spreafico F. Selected pharmacologic characteristics of idarubicin and idarubicinol. Leukemia 1992; 6 Suppl. 1: 70–5

    PubMed  Google Scholar 

  10. Di Marco A, Casazza AM, Pratesi G. Antitumor activity of 4-demethoxydaunorubicin administered orally. Cancer Treat Rep 1977 Aug; 61(5): 893–4

    PubMed  Google Scholar 

  11. Bigioni M, Zunino F, Capranico G. Base mutation analysis of topoisomerase II-idarubicin-DNA ternary complex formation: evidence for enzyme subunit cooperativity in DNA cleavage. Nucleic Acids Res 1994 Jun 25; 22: 2274–81

    PubMed  CAS  Google Scholar 

  12. Smith PJ, Rackstraw C, Cotter F. DNA fragmentation as a consequence of cell cycle traverse in doxorubicin- and idarubicin-treated human lymphoma cells. Ann Hematol 1994; 69(1): S7–11

    PubMed  CAS  Google Scholar 

  13. Gieseler F, Biersack H, Brieden T, et al. Cytotoxicity of anthracyclines: correlation with cellular uptake, intracellular distribution and DNA binding. Ann Hematol 1994; 69 Suppl. 1: SI 3–7

    Google Scholar 

  14. Damiani D, Michieli M, Michelutti A, et al. P170 glycoprotein expression and impaired anthracycline retention in chronic myeloid leukaemia. Leuk Lymphoma 1995 Apr; 17: 289–94

    PubMed  CAS  Google Scholar 

  15. Miller TP, Grogan TM, Dalton WS, et al. P-Glycoprotein expression in malignant lymphoma and reversal of clinical drug resistance with chemotherapy plus high-dose verapamil. J Clin Oncol 1991 Jan; 9(1): 17–24

    PubMed  CAS  Google Scholar 

  16. Mankhetkorn S, Dubru F, Hesschenbrouck J, et al. Relation among the resistance factor, kinetics of uptake, and kinetics of the P-glycoprotein-mediated efflux of doxorubicin, daunorubicin, 8- (S)-fluoroidarubicin, and idarubicin in multidrug-resistant K562 cells. Mol Pharmacol 1996 Mar; 49: 532–9

    PubMed  CAS  Google Scholar 

  17. Toffoli G, Simone F, Gigante M, et al. Comparison of mechanisms responsible for resistance to idarubicin and daunorubicin in multidrug resistant LoVo cell lines. Biochem Pharmacol 1994 Nov 16; 48: 1871–81

    PubMed  CAS  Google Scholar 

  18. Toffoli G, Corona G, Simone F, et al. Cellular pharmacology of idarubicinol in multidrug-resistant LoVo cell lines. Int J Cancer 1996 Jul 3; 67: 129–37

    PubMed  CAS  Google Scholar 

  19. Michieli M, Michelutti A, Damiani D, et al. A comparative analysis of the sensitivity of multidrug resistant (MDR) and non-MDR cells to different anthracycline derivatives. Leuk Lymphoma 1993 Feb; 9: 255–64

    PubMed  CAS  Google Scholar 

  20. Tidefelt U, Prenkert M, Paul C. Comparison of idarubicin and daunorubicin and their main metabolites regarding intracellular uptake and effect on sensitive and multidrug-resistant HL60 cells. Cancer Chemother Pharmacol 1996; 38(5): 476–80

    PubMed  CAS  Google Scholar 

  21. Ross DD, Doyle LA, Yang W, et al. Susceptibility of idarubicin, daunorubicin, and their C-13 alcohol metabolites to transport-mediated multidrug resistance. Biochem Pharmacol 1995 Nov 9; 50: 1673–83

    PubMed  CAS  Google Scholar 

  22. Hegewisch-Becker S. MDR1 reversal: criteria for clinical trials designed to overcome the multidrug resistance phenotype. Leukemia 1996 Jul; 10 Suppl. 3: S32–8

    PubMed  Google Scholar 

  23. Hegewisch-Becker S, Hossfeld DK. The MDR phenotype in hematologic malignancies: prognostic relevance and future perspectives. Ann Hematol 1996; 72: 105–17

    PubMed  CAS  Google Scholar 

  24. Boiron JM, Belloc F, Montastruc M, et al. Flow cytometric study of idarubicin and daunorubicin accumulation and the effect of verapamil in leukemic cell lines and fresh cells from patients with acute non-lymphoblastic leukemia. Leuk Res 1994 May; 18: 313–8

    PubMed  CAS  Google Scholar 

  25. Damiani D, Michieli M, Michelutti A, et al. D-Verapamil downmodulates P170-associated resistance to doxorubicin, daunorubicin and idarubicin. Anticancer Drugs 1993 Apr; 4: 173–80

    PubMed  CAS  Google Scholar 

  26. Michieli M, Damiani D, Michelutti A, et al. Restoring uptake and retention of daunorubicin and idarubicin in P170-related multidrug resistance cells by low concentration D-verapamil, cyclosporin-A and SDZ PSC 833. Haematologica 1995; 79(6): 500–7

    Google Scholar 

  27. Tolomeo M, Gancitano RA, Musso MM, et al. Effects of idarubicin and idarubicinol in combination with cyclosporin A in cells displaying the multidrug resistant (MDR) phenotype. J Exp Clin Cancer Res 1995; 14 Suppl. 1: 134–5

    Google Scholar 

  28. Grey MR, Burgess R, Fisher A, et al. Idarubicin is superior to daunorubicin when used with the multidrug resistance modifier, PSC 833, in acute myeloid leukaemia [abstract]. Br J Haematol 1996 Apr; 93 Suppl. 1: 64

    Google Scholar 

  29. Camaggi CM, Strocchi E, Carisi P, et al. Idarubicin metabolism and pharmacokinetics after intravenous and oral administration in cancer patients: a crossover study. Cancer Chemother Pharmacol 1992 Aug; 30: 307–16

    PubMed  CAS  Google Scholar 

  30. Eksborg S, Söderberg M, Nilsson B, et al. Plasma pharmacokinetics of idarubicin and its 13-hydroxymetabolite after intra-venous and oral administration under fasting and non-fasting conditions. Acta Oncol 1990; 29(7): 921–5

    PubMed  CAS  Google Scholar 

  31. Elbaek K, Ebbehøj E, Jakobsen A, et al. Pharmacokinetics of oral idarubicin in breast cancer patients with reference to an-titumor activity and side effects. Clin Pharmacol Ther 1989 Jun; 45: 627–34

    PubMed  CAS  Google Scholar 

  32. Pannuti F, Camaggi CM, Strocchi E, et al. Low dose oral administration of 4-demethoxy-daunorubicin (idarubicin) in advanced cancer patients. Cancer Chemother Pharmacol 1986; 16(3): 295–9

    PubMed  CAS  Google Scholar 

  33. Smith DB, Margison JM, Lucas SB, et al. Clinical pharmacology of oral and intravenous 4-demethoxydaunorubicin. Cancer Chemother Pharmacol 1987; 19: 138–42

    PubMed  CAS  Google Scholar 

  34. Stewart DJ, Grewaal D, Green RM, et al. Bioavailability and pharmacology of oral idarubicin. Cancer Chemother Pharmacol 1991 Jan; 27: 308–14

    PubMed  CAS  Google Scholar 

  35. Tamassia V, Pacciarini MA, Moro E, et al. Pharmacokinetic study of intravenous and oral idarubicin in cancer patients. Int J Clin Pharmacol Res 1987; 7(5): 419–26

    PubMed  CAS  Google Scholar 

  36. Gillies HC, Herriot D, Liang R, et al. Pharmacokinetics of idarubicin (4-demethoxydaunorubicin; IMI-30; NCS 256439) following intravenous and oral administration in patients with advanced cancer. Br J Clin Pharmacol 1987 Mar; 23(3): 303–10

    PubMed  CAS  Google Scholar 

  37. Zanette L, Zucchetti M, Freshi A, et al. Pharmacokinetics of 4-demethoxydaunorubicin in cancer patients. Cancer Chemother Pharmacol 1990; 25: 445–8

    PubMed  CAS  Google Scholar 

  38. Friche E, Jensen PB, Roed H, et al. In vitro circumvention of anthracycline resistance in Ehrlich ascites tumour by anthra-cycline analogues. Biochem Pharmacol 1990; 39: 1721–6

    PubMed  CAS  Google Scholar 

  39. Robert J. Clinical pharmacokinetics of idarubicin. Clin Phar-macokinet 1993 Apr; 24: 275–88

    CAS  Google Scholar 

  40. Speth PAJ, van de Loo FAJ, Linssen PCM, et al. Plasma and human leukemic cell pharmacokinetics of oral and intravenous 4-demethoxydaunomycin. Clin Pharmacol Ther 1986 Dec; 40(6): 643–9

    PubMed  CAS  Google Scholar 

  41. Lasota WS, de Valeriola DL, Piccart MJ. Potential role of oral anthracyclines in older patients with cancer. Drugs Aging 1994 May; 4: 392–402

    PubMed  CAS  Google Scholar 

  42. Robert J, Rigal-Huguet F, Huet S, et al. Pharmacokinetics of idarubicin after oral administration in elderly leukemic patients. Leukemia 1990 Mar; 4: 227–9

    PubMed  CAS  Google Scholar 

  43. Robert J, Gianni L. Pharmacokinetics and metabolism of anthracyclines. Cancer Surv 1993; 17: 219–52

    PubMed  CAS  Google Scholar 

  44. Berman E, Wittes RE, Leyland-Jones B, et al. Phase I and clinical pharmacology studies of intravenous and oral administration of 4-demethoxydaunorubicin in patients with advanced cancer. Cancer Res 1983 Dec; 43: 6096–101

    PubMed  CAS  Google Scholar 

  45. Robert J, Rigal-Huguet F, Hurteloup P. Comparative pharmacokinetic study of idarubicin and daunorubicin in leukemia patients. Hematol Oncol 1992 Mar-Apr; 10: 111–6

    PubMed  CAS  Google Scholar 

  46. Strolin Benedetti M. Pharmacokinetics and metabolism of oral idarubicin. Res Clin Forum 1996; 18(3): 11–8

    Google Scholar 

  47. Camaggi CM, Carisi P, Strocchi E, et al. High-performance liquid Chromatographic analysis of idarubicin and fluorescent metabolites in biological fluids. Cancer Chemother Pharmacol 1992; 30: 303–6

    PubMed  CAS  Google Scholar 

  48. Alberts AS, Falkson G, Rapoport BL, et al. A phase II study of idarubicin and prednisone in multiple myeloma. Tumori 1990 Oct 31; 76: 465–6

    PubMed  CAS  Google Scholar 

  49. Hochster H, Green M, Liebes L, et al. Good tolerance of weekly oral idarubicin (4-demethoxydaunorubicin): a phase I study with pharmacology. Cancer Chemother Pharmacol 1990 Jul; 26: 297–300

    PubMed  CAS  Google Scholar 

  50. Harousseau JL. Oral agents for the treatment of AML: clinical experience with oral idarubicin. Res Clin Forum 1996; 18(3): 45–51

    Google Scholar 

  51. Burnett AK, Eden OB. The treatment of acute leukaemia. Lancet 1997 Jan 25; 349: 270–5

    PubMed  CAS  Google Scholar 

  52. Keldsen N, Karle H, Hansen NE, et al. Oral idarubicin in elderly patients with acute myeloid leukemia [letter]. Eur J Haematol 1990 Jul; 45: 60

    PubMed  CAS  Google Scholar 

  53. Musso M, Porretto F, Crescimanno A, et al. Maintenance low-dose oral idarubicin in elderly patients with acute myeloge-nous leukemia [abstract]. Eur J Cancer 1996; 32A Suppl. 1: 14

    Google Scholar 

  54. Berrebi A, Polliack A. Oral idarubicin in elderly acute leukemia and myelodysplastic syndromes. Leuk Lymphoma 1990; 2(5): 287–90

    Google Scholar 

  55. Boulat O, Chami S, Zerazhi H, et al. Faut-il traiter les leucemies aigues du sujet âgé de plus de 60 ans en 1995? Bull Cancer 1995; 82(6): 444

    Google Scholar 

  56. Harousseau JL, Rigal-Huguet F, Hurteloup P, et al. Treatment of acute myeloid leukemia in elderly patients with oral idarubicin as a single agent. Eur J Haematol 1989 Feb; 42: 182–5

    PubMed  CAS  Google Scholar 

  57. Lowenthal RM, Chesterman CN, Griffiths JD, et al. Oral idarubicin as single-agent treatment of acute nonlymphocytic leukemia in poor-risk patients. Cancer Treat Rep 1987 Dec; 71(12): 1279–81

    PubMed  CAS  Google Scholar 

  58. Musso M, Iannitto E, Quintini G, et al. Acute leukemia in elderly: treatment with oral idarubicin [abstract no. 186]. Eur J Cancer 1994; 30 Suppl. 1: 37

    Google Scholar 

  59. Harousseau JL, Huguet F, Reiffers J, et al. Oral idarubicin and low dose cytarabine as the initial treatment of acute myeloid leukemia in elderly patients. Leuk Lymphoma 1991; 15(2-3): 145–9

    Google Scholar 

  60. Helg C, Chapuis B, Grob J-P, et al. Poor risk acute myelogenous leukemia: treatment with a combination of oral idarubicin and low dose subcutaneous cytarabine [in French]. Schweiz Med Wochenschr 1990 Apr 14; 120: 548–52

    PubMed  CAS  Google Scholar 

  61. Pagano L, Sica S, Marra R, et al. Oral idarubicin plus cytosine arabinoside in the treatment of acute nonlymphoblastic leukemia in elderly patients. Haematologica 1991 Nov-Dec; 76: 517–8

    PubMed  CAS  Google Scholar 

  62. Taylor PRA, Jackson GH, Turner G, et al. The use of an all-oral chemotherapy (idarubicin and etoposide) in the treatment of acute myeloid leukaemia in the elderly: a report of toxicity and efficacy [abstract]. Br J Haematol 1996 Apr; 93 Suppl. 1: 64

    Google Scholar 

  63. Visentin FCA, Ganzina F, Smeets J, et al. Oral idarubicin in elderly patients with acute myelogenous leukemia: an opportunity? [abstract no. 73P] Eur J Cancer 1996; 32A Suppl. 1: 14

    Google Scholar 

  64. Ruutu T, Finnish Leukaemic Group. Results of a randomised comparison of oral etoposide, thioguanine and idarubicin (ETI) with thioguanine, cytarabine and daunorubicin (TAD) in elderly patients with acute myeloid leukaemia. Res Clin Forum 1996; 18(3): 53–8

    Google Scholar 

  65. Avvisati G, Lo Coco F, Diverio D, et al. AIDA (a11-trans retinoic acid + idarubicin) in newly diagnosed acute promyelocytic leukemia: a Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto (GIMEMA) Pilot Study. Blood 1996 Aug 15; 88: 1390–8

    PubMed  CAS  Google Scholar 

  66. Lo Coco F, Diverio D, Avvisati G, et al. High frequency of early molecular remission in acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (Italian GIMEMA-AIEOP ‘AIDA’ trial) [abstract]. Blood 1995 Nov 15; 86 Suppl. 1: 265a

    Google Scholar 

  67. Avvisati G, Mandelli F, Petti MC, et al. Idarubicin (4-demethoxydaunorubicin) as single agent for remission induction of previously untreated acute promyelocytic leukemia: a pilot study of the Italian cooperative group GIMEMA. Eur J Haematol 1990 Apr; 44: 257–60

    PubMed  CAS  Google Scholar 

  68. Berrebi A, Polliack A. Oral idarubicin in elderly acute leukemia and refractory anemia with excess of blasts. Heamatol Bluttransfus 1990; 33: 342–5

    CAS  Google Scholar 

  69. De Bock R, Van Hoof A, Van Hove W, et al. Oral idarubicin (IDA) for RAEB, RAEBt and acute leukemia (AL) post myelodysplastic syndrome (MDS): a phase II open study [abstract no. 794]. Proceedings of the 25th Annual Meeting of the American Society of Clinical Oncology; 1989 Mar; 8: 204

  70. Greenberg BR, Reynolds RD, Charron CB, et al. Treatment of myelodysplastic syndromes with daily oral idarubicin: a phase I-II study. Cancer 1993 Mar 15; 71: 1989–92

    PubMed  CAS  Google Scholar 

  71. Johnson E, Parapia LA. Successful oral chemotherapy with idarubicin in refractory anaemia with excess blasts. Eur J Haematol 1987; 39(3): 278–81

    PubMed  CAS  Google Scholar 

  72. Lowenthal RM, Lambertenghi-Deliliers G. Oral idarubicin as treatment for advanced myelodysplastic syndrome. Haematologica 1991 Sep-Oct; 76: 398–401

    PubMed  CAS  Google Scholar 

  73. Kelsey SM, Somasundram U, Hazel D, et al. Oral idarubicin and GM-CSF for the treatment of myelodysplastic syndromes [abstract]. Br J Haematol 1996 Apr; 93 Suppl. 1: 20

    Google Scholar 

  74. Morrison VA. Chronic leukemias. CA Cancer J Clin 1994 Nov-Dec; 44: 353–77

    PubMed  CAS  Google Scholar 

  75. Carella AM, Frassoni F, Podestà M, et al. Idarubicin, intermediate-dose cytarabine, etoposide, and granulocyte-colony-stimulating factor are able to recruit CD34+/HLA-DR-cells during early hematopoietic recovery in accelerated and chronic phases of chronic myeloid leukemia. J Hematother 1994 Fall; 3: 199–202

    PubMed  CAS  Google Scholar 

  76. Glasmacher A, Steinmetz HT, Kleinschmidt R, et al. Treatment of chronic myeloid leukaemia blast crisis with fludarabine, cytarabine, filgrastim and idarubicin (FLAG-IDA) [abstract]. Onkologie 1995 Oct; 18 Suppl. 2: 144

    Google Scholar 

  77. Lambertenghi-Deliliers G, Annaloro C, Cortellaro M, et al. Idarubicin in blastic crisis of chronic myelogenous leukemia. Haematologica 1991 Sep-Oct; 76: 406–8

    PubMed  CAS  Google Scholar 

  78. Davis CL, Rohatiner AZS, Amess JAL, et al. Oral idarubicin as a palliative agent in leukemia. Hematol Oncol 1991 Jan-Feb; 9: 59–60

    PubMed  CAS  Google Scholar 

  79. Choy CG, Niesvizky R, Michaeli J. Multiple myeloma: treatment recommendations. Clin Immunother 1995 Nov; 4: 346–60

    Google Scholar 

  80. Cook G, Sharp RA, Tansey P. A phase I/II trial of Z-Dex (oral idarubicin and dexamethasone), an oral equivalent of VAD, as initial therapy at diagnosis or progression in multiple myeloma. Br J Haematol 1996 Jun; 93 (Pt 2): 931–4

    PubMed  CAS  Google Scholar 

  81. Anderson H, Scarffe JH, Ranson M, et al. VAD chemotherapy as remission induction for multiple myeloma. Br J Cancer 1995; 71: 326–30

    PubMed  CAS  Google Scholar 

  82. Chisesi T, Capnist G, de Dominicis E, et al. A phase II study of idarubicin (4-demethoxydaunorubicin) in advanced myeloma. Eur J Cancer Clin Oncol 1988 Apr; 24: 681–4

    PubMed  CAS  Google Scholar 

  83. Franklin IM. Z-DEX (oral idarubicin and dexamethasone) in multiple myeloma [abstract]. ‘Emerging trends in the management of hematological malignancies’ 2nd Meeting of the European Haematology Association; 1996 May 31; Paris, France

  84. Gupta D, Kelsey SM, Littlewood TJ, et al. Oral idarubicin with CCNU and dexamethasone for relapsed myeloma: an effective oral regimen with minimal toxicity [abstract]. Br J Haematol 1996 Jun; 93 Suppl. 2: 301

    Google Scholar 

  85. Glasmacher A, Gieseler F, Haferlach T, et al. Oral idarubicin, vincristine and dexamethasone (VID) in the treatment of refractory and relapsed multiple myeloma [abstract no. 39]. Proceedings of the 33rd Annual Meeting of the American Society of Clinical Oncology; 1997 May 17-20; Denver, USA

  86. Brugnatelli S, Riccardi A, Ucci G, et al. Oral idarubicin and prednisone for advanced, previously untreated, multiple myeloma: a pilot study. Ann Oncol 1996 Jul; 7: 537–8

    PubMed  CAS  Google Scholar 

  87. Brugnatelli S, Riccardi A, Ucci G, et al. First line treatment for stage III, multiple myeloma (MM) with oral idarubicin (IDA) and prednisone (P) [abstract no. 289]. Tumori 1996 Jul-Aug; 82 Suppl.: 107

    Google Scholar 

  88. Eridani S, Slater NGP, Singh AK, et al. Intravenous and oral demethoxydaunorubicin (NSC256-439) in the treatment of acute leukemia and lymphoma: a pilot study. Blut 1985 Jun; 50: 369–72

    PubMed  CAS  Google Scholar 

  89. Case Jr DC, Hayes DM, Gerber M, et al. Phase II study of oral idarubicin in favorable histology non-Hodgkin’s lymphoma. Cancer Res 1990 Nov 1; 50: 6833–5

    PubMed  Google Scholar 

  90. Lopez M, di Lauro L, Papaldo P. Oral idarubicin in non-Hodgkin’s lymphomas. Invest New Drugs 1986; 4: 263–7

    PubMed  CAS  Google Scholar 

  91. Errante D, Sorio R, Zagonel V, et al. A phase II study of oral idarubicin (4-demethoxidaunorubicin) in previously untreated elderly patients with non-Hodgkin’s lymphoma. Am J Clin Oncol Cancer Clin Trials 1991 Jun; 14: 243–5

    CAS  Google Scholar 

  92. Steward WP, Smith DB, Crowther D. Weekly oral 4-demethoxydaunorubicin in patients with relapsed low grade non-Hodgkin’s lymphoma. Ann Oncol 1991 Sep; 2: 605–6

    PubMed  CAS  Google Scholar 

  93. Proctor SJ, Taylor PRA. The use of oral idarubicin, chlorambu-cil and dexamethasone in low-grade non-Hodgkin’s lymphoma. Res Clin Forum 1996; 18(3): 29–34

    Google Scholar 

  94. Mileti A, Pavone V, Guarini A, et al. Association of idarubicin and prednimustine. Preliminary study of 25 patients with non-Hodgkin’s lymphoma in the advanced stage [in Italian]. Haematologica 1994 Jan-Feb; 79 Suppl. 1: 130–2

    Google Scholar 

  95. de Graaf H, Willemse PHB, Sleijfer DT. Review: breast cancer in elderly patients. Age Ageing 1994; 23(5): 427–34

    PubMed  Google Scholar 

  96. 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 Cancer Clin Trials 1990 Oct; 13: 436–9

    CAS  Google Scholar 

  97. 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 May; 71(5): 451–4

    PubMed  CAS  Google Scholar 

  98. 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 Dec; 71(12): 1289–90

    PubMed  CAS  Google Scholar 

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

    PubMed  Google Scholar 

  100. Hurteloup P, Armand JP, Schneider M, et al. Phase II trial of idarubicin (4-demethoxydaunorubicin) in advanced breast cancer. The Clinical Screening Group of the European Organization for Research and Treatment of Cancer. Eur J Cancer Clin Oncol 1989 Mar; 25: 423–8

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  102. Lionetto R, Pronzato P, Conte PF, et al. Idarubicin in advanced breast cancer: a phase II study. Cancer Treat Rep 1986 Dec; 70(12): 1439–40

    PubMed  CAS  Google Scholar 

  103. Lopez M, di Lauro L, Papaldo P, et al. Phase II trial with oral idarubicin in advanced breast cancer. Invest New Drugs 1986; 4(1): 39–42

    PubMed  CAS  Google Scholar 

  104. Martoni A, Pacciarini MA, Pannuti F. The new anthracycline 4-demethoxydaunorubicin by oral route in advanced pre-treated breast cancer and melanoma: a pilot study. Drugs Exp Clin Res 1985; 11(2): 127–31

    PubMed  CAS  Google Scholar 

  105. Possinger K, Wagner H, Worst P, et al. Oral administration of idarubicin as first line cytostatic therapy in patients with me-tastasized 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 Feb; 14: 31–4

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  107. 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

    PubMed  CAS  Google Scholar 

  108. Bastholt L, Dalmark M, Jakobsen A, et al. Weekly oral idarubicin in postmenopausal women with advanced breast cancer: a phase II study. Acta Oncol 1990; 29: 143–6

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  110. Campos D, Puricelli G, Matweijuk M, et al. Antitumor activity of oral idarubicin in postmenopausal patients (pts) with met-astatic breast cancer (mbc) [abstract no. 262]. Proc Am Soc Clin Oncol 1995; 14: 141

    Google Scholar 

  111. 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 Dec 15; 64: 2431–6

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  113. Kolaric K, Mechl Z. Combination of idarubicin and cyclophos-phamide administered orally in untreated postmenopausal breast cancer patients: a phase II study. Oncology 1991 Mar-Apr; 48: 93–6

    PubMed  CAS  Google Scholar 

  114. 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(1): 61–4

    PubMed  CAS  Google Scholar 

  115. Marshall E, Mackay J, Ranson M, et al. Oral regimen, idarubicin (IDA) plus cyclophosphamide (CTX) in advanced breast cancer (ABC) patients (Pts): preliminary results of a phase I-II trial [abstract]. Proc Am Soc Clin Oncol 1995 Mar; 14: 141

    Google Scholar 

  116. Pronzato P, Bertelli G, Amoroso D, et al. Oral chemotherapy with idarubicin plus cyclophosphamide in advanced breast cancer. Chemotherapy Basel 1991 Nov-Dec; 37: 449–53

    CAS  Google Scholar 

  117. Barnadas A, Mendiola C, Casado A, et al. Combination of oral idarubicin and prednimustine in advanced breast cancer: a phase II study. Eur J Cancer 1997; 33(2): 313–5

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  119. Cersosimo RJ. Idarubicin: an anthracycline antineoplastic agent. Clin Pharm 1992 Feb; 11: 152–67

    PubMed  CAS  Google Scholar 

  120. Bonfante V, Ferrari L, Brambilla C, et al. New anthracyclone analogs in advanced breast cancer. Eur J Cancer Clin Oncol 1986; 22(11): 1379–85

    PubMed  CAS  Google Scholar 

  121. Villani F, Galimberti M, Comazzi R, et al. Evaluation of cardiac toxicity of idarubicin (4-demethoxydaunorubicin). Eur J Cancer Clin Oncol 1989 Jan; 25: 13–8

    PubMed  CAS  Google Scholar 

  122. Bertelli G, Amoroso D, Pronzato P, et al. Idarubicin: an evaluation of cardiac toxicity in 77 patients with solid tumors. An-ticancer Res 1988 Jul-Aug; 8: 645–6

    CAS  Google Scholar 

  123. Case Jr DC. Safety of oral idarubicin. Clin Drug Invest 1995; 9 Suppl. 2: 9–15

    Google Scholar 

  124. Goebel M. Oral idarubicin — an anthracycline derivative with unique properties. Ann Hematol 1993 Jan; 66: 33–43

    PubMed  CAS  Google Scholar 

  125. Keating MJ. Oral idarubicin in haematological malignancies: putative indications. Clin Drug Invest 1995; 9 Suppl. 2: 29–38

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Micaela M. Buckley & Harriet M. Lamb

Authors
  1. Micaela M. Buckley
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Harriet M. Lamb
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Harriet M. Lamb.

Additional information

Various sections of the manuscript reviewed by: A.M. Carella, Hematology and Autologous BMT Unit, Azienda Ospedaliera Ospedale San Martino, Genoa, Italy; D.C. Case Jr, Maine Cancer Center for Medicine, Portland, Maine, USA; A. Glasmacher, Medizinische Klinik und Poliklinik — Allgemeine Innere Medizin, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany; J.L. Harousseau, Service d’Hematologie Clinique, Centre Hospitalier Universitaire de Nantes, Nantes, France; M.J. Keating, M.D. Anderson Cancer Center, University of Texas, Houston, Texas, USA; G. Lambertenghi-Deliliers, Istituto di Scienze Mediche, Milan, Italy; M. Lopez, Divisione di Oncologia Medica II, Istituto Regina Elena, Rome, Italy; R.M. Lowenthal, Clinical Haematology and Medical Oncology Unit, Royal Hobart Hospital, Hobart, Tasmania, Australia; F. Mandelli, Sezione Ematologia, Dipartimento di Biopatologia Umana, Universita delgi Studi ‘La Sapienza’, Rome, Italy; A. Riccardi, Dipartimento di Medicina Intema e Terapia Medica, Universita di Pavia, Pavia, Italy; T. Ruutu, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Buckley, M.M., Lamb, H.M. Oral Idarubicin. Drugs & Aging 11, 61–86 (1997). https://doi.org/10.2165/00002512-199711010-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-199711010-00006

Keywords

Search

Navigation