Skip to main content
SpringerLink
Log in

Oral Fludarabine

  • Adis Drug Profile
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

  • ▴ Fludarabine is an antimetabolite antineoplastic agent used in the treatment of various haematological malignancies, particularly B-cell chronic lymphocytic leukaemia (CLL).

  • ▴ An oral formulation of fludarabine has recently become available in the majority of European countries for the treatment of patients with relapsed or refractory B-cell CLL after initial treatment with an alkylating agent-based regimen. It is the first oral formulation of a purine analogue available for clinical use in B-cell CLL.

  • ▴ Pharmacokinetic studies evaluating the bioavailability of oral fludarabine indicate that an oral dose of 40 mg/m2/day would provide similar systemic drug exposure to the standard intravenous dose of 25 mg/m2/day.

  • ▴ A phase II study evaluated the clinical efficacy of six to eight cycles of oral fludarabine 40 mg/m2/day for 5 days of each 28-day cycle in 78 patients with previously treated B-cell CLL. Depending on the criteria used, the overall response rate was 46.2% (20.5% complete response [CR], 25.6% partial response [PR]) or 51.3% (17.9% CR, 33.3% PR). These results were similar to the 48% overall response rate reported in a similar historical control group treated with intravenous fludarabine.

  • ▴ Myelosuppression (WHO grade 3 or 4) was the most frequently reported adverse effect with oral fludarabine therapy. Other common adverse effects included infection and gastrointestinal disturbances, although these were usually of mild to moderate severity (WHO grade 1 or 2). Overall, the tolerability profile of oral fludarabine is similar to that of the intravenous formulation.

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

Fig. 1
Fig. 2

Similar content being viewed by others

Notes

  1. Use of tradenames is for identification purposes only and does not imply product endorsement.

References

  1. Adkins JC, Peters DH, Markham A. Fludarabine: an update of its pharmacology and use in the treatment of haematological malignancies. Drugs 1997 Jun; 53(6): 1005–37

    PubMed  CAS  Google Scholar 

  2. National Cancer Institute. Chronic lymphocytic leukemia (PDQ®): treatment [online]. Available from URL: http://www.cancer.gov/cancer_information/ [Accessed 2003 Jul 15]

  3. National Institute for Clinical Excellence. Technology Appraisal Guidance. No. 29. Guidance on the use of fludarabine for B-cell chronic lymphocytic leukaemia. London: National Institute for Clinical Excellence, 2001 Sep: 14

    Google Scholar 

  4. Schering AG. Fludara® (fludarabine phosphate) receives marketing approval in the UK as first-line treatment for B-cell chronic lymphocytic leukemia (media release 2003 Feb 11) [online]. Available from URL: http://www.schering.co.uk [Accessed 2003 Jun 12]

  5. Kalil N, Cheson BD. Management of chronic lymphocytic leukaemia. Drugs Aging 2000 Jan; 16: 9–27

    Article  PubMed  CAS  Google Scholar 

  6. Kay NE, Hamblin TJ, Jelinek DF, et al. Chronic lymphocytic leukemia. Hematology (Am Soc Hematol Educ Program) 2002, 193-213

  7. Montserrat E. Current and developing chemotherapy for CLL. Med Oncol 2002; 19 Suppl.: S11–9

    Article  PubMed  Google Scholar 

  8. Hamblin TJ. Achieving optimal outcomes in chronic lymphocytic leukaemia. Drugs 2001; 61(5): 593–611

    Article  PubMed  CAS  Google Scholar 

  9. Keating MJ. Chronic lymphocytic leukemia. Semin Oncol 1999; 26 Suppl. 14(5): 107–14

    PubMed  CAS  Google Scholar 

  10. Schering AG. Schering launches oral formulation of Fludara® (media release 2003 Jan 22) [online]. Available from URL: http://www.schering.co.uk [Accessed 2003 Jun 9]

  11. British National Formulary. 45th edition ed. London: British Medical Association and Royal Pharmaceutical Society of Great Britain, 2003

  12. Gandhi V, Plunkett W. Cellular and clinical pharmacology of fludarabine. Clin Pharmacokinet 2002; 41(2): 93–103

    Article  PubMed  CAS  Google Scholar 

  13. O’Rourke TJ, Burris HA, Rodriguez GI, et al. Phase I pharmacokinetic and bioavailability study of five daily intravenous and oral doses of fludarabine phosphate in patients with advanced cancer [abstract no. 736]. 33rd Annual Meeting of the American Society of Clinical Oncology; 1997 May 17–20; Denver, 210a

  14. Kemena A, Keating M, Plunkett W. Plasma and cellular bioavailability of oral fludarabine [abstract no. 199]. Blood 1991 Nov 15; Suppl. 1(10): 52a

    Google Scholar 

  15. Kemena A, Keating M, Plunkett W. Oral bioavailability of plasma fludarabine and fludarabine triphosphate (F-ara-ATP) in peripheral CLL cells [abstract no. 238]. Onkologie 1991 Oct; 14 (Suppl. 2): 83

    Google Scholar 

  16. Oscier D, Orchard JA, Culligan D, et al. The bioavailability of oral fludarabine phosphate is unaffected by food. Hematol J 2001; 2(5): 316–21

    Article  PubMed  CAS  Google Scholar 

  17. Foran JM, Oscier D, Orchard J, et al. Pharmacokinetic study of single doses of oral fludarabine phosphate in patients with “low-grade” non-Hodgkin’s lymphoma and B-cell chronic lymphocytic leukemia. J Clin Oncol 1999 May; 17(5): 1574–9

    PubMed  CAS  Google Scholar 

  18. Klein M, Ludwig W-D, Fülle HH, et al. 2F-ara-A pharmacokinetics including systemic availability during treatment with fludarabine phosphate given either perorally as an immediate release tablet formulation or intravenously as a solution [abstract no. 525]. Ontologie 1997 Oct; 20 Suppl. 1: 137

    Google Scholar 

  19. Boogaerts MA, Van Hoof A, Catovsky D, et al. Activity of oral fludarabine phosphate in previously treated chronic lymphocytic leukemia. J Clin Oncol 2001 Nov 15; 19(22): 4252–8

    PubMed  CAS  Google Scholar 

  20. Johnson S, Smith AG, Löffler H, et al. Multicentre prospective randomised trial of fludarabine versus cyclophosphamide, doxorubicin, and prednisone (CAP) for treatment of advancedstage chronic lymphocytic leukaemia. The French Cooperative Group on CLL. Lancet 1996; 347: 1432–8

    CAS  Google Scholar 

  21. Rossi J-F, Van Hoof A, De Bock R, et al. Oral fludarabine phosphate as first-line treatment of chronic lymphocytic leukemia [abstract no. 1491 plus poster no. 657-1]. Blood 2002 Nov 16; 100(11 Pt 1): 384–5

    Article  Google Scholar 

  22. Cazin B, Maloum K, Divine M, et al. Oral fludarabine and cyclophosphamide in previously untreated CLL: preliminary data on 75 pts [abstract no. 773]. Blood 2002 Nov 16; 100 (11 Pt 1): 206a

    Google Scholar 

  23. Mosby’s Drug Consult: Fludarabine phosphate [online]. Available from URL: http://www.mosbydrugs.com [Accessed 2003 Jul 7]

  24. Cid J, Revilla M, Cervera A, et al. Progressive multifocal leukoencephalopathy following oral fludarabine treatment of chronic lymphocytic leukemia. Ann Hematol 2000 Jul; 79(7): 392–5

    Article  PubMed  CAS  Google Scholar 

  25. Cohen RB, Abdallah JM, Gray JR, et al. Reversible neurologic toxicity in patients treated with standard-dose fludarabine phosphate for mycosis fungoides and chronic lymphocytic leukemia. Ann Intern Med 1993; 118: 114–6

    PubMed  CAS  Google Scholar 

  26. Johnson PWM, Fearnley J, Domizio P, et al. Neurological illness following treatment with fludarabine. Br J Cancer 1994; 70: 966–8

    Article  PubMed  CAS  Google Scholar 

  27. Zabernigg A, Maier H, Thaler J, et al. Late-onset fatal neurological toxicity of fludarabine [letter]. Lancet 1994; 344: 1780

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 1311, New Zealand

    Greg L. Plosker & David P. Figgitt

Authors
  1. Greg L. Plosker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David P. Figgitt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Greg L. Plosker.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Plosker, G.L., Figgitt, D.P. Oral Fludarabine. Drugs 63, 2317–2323 (2003). https://doi.org/10.2165/00003495-200363210-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200363210-00004

Keywords

Search

Navigation