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Flexible Low-Intensity Combination Chemotherapy for Elderly Patients with Acute Myeloid Leukaemia

A Multicentre, Phase II Study

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Abstract

Objective

To evaluate the efficacy of a flexible low-intensity combination chemotherapy (FLICC) protocol in a multicentre, phase II study of elderly patients with acute myeloid leukaemia (AML).

Method

Twenty-five patients aged 61–78 years (median 70 years) with de novo (n = 17) or secondary (n = 8) AML (cytogenetic risk: favourable 2, intermediate 18, adverse 2, unknown 3) from eight Australian centres were enrolled. Treatment comprised mitoxantrone 6 mg/m2 intravenously daily for 3 days, cytarabine 10mg/m2 subcutaneously every 12 hours for 7–14 days and etoposide 100mg orally for 7–14 days.

Results

The treatment was generally well tolerated, and 13 patients (52%) achieved a complete remission (CR). One patient achieved a partial remission but died on day 28 due to pneumonia. Five patients (20%) had no response, whilst six (24%) died on or before day 30 and so were not evaluable. The median overall survival (OS) was 6.5 months, and the median remission duration was 7.7 months. Estimated 1-year survival was 32%, but patients achieving CR had an estimated 1-year survival of 64%, whereas none in the non-CR group survived to 1 year. Two of the CR patients have survived beyond 2 years. OS was significantly shorter in the adverse cytogenetic risk group of patients compared with the favourable- and intermediate-risk groups, with the rates of death relative to the adverse group being 0.02 and 0.08 in the favourable- and intermediate-risk groups, respectively. There was no significant association between CR rate and pre-existing myelodysplasia or the presence of multilineage dysplasia.

The median durations of significant neutropenia (<0.5 × 109/L) and thrombocytopenia (<20 × 109/L) with the first course of treatment in the 19 evaluable patients were 19 days (range 12–26) and 11 days (range 1–25), respectively. The median duration of stay in the hospital was 27 days (range 14–2). These values were much shorter for the second course of treatment: 6 days, 5 days and 15 days, respectively.

Conclusion

The findings of this multicentre, phase II study validate the previously reported single-institution experience with the FLICC protocol in elderly patients with AML. The clinical outcome with this protocol is comparable to those reported with more aggressive anti-leukaemia protocols.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

No sources of funding were used to assist in the preparation of this study. The authors have no conflicts of interest that are directly relevant to the content of this study.

The following centres and clinical haematologists participated in this study: Fremantle Hospital, Fremantle, Western Australia (M. Leahy, F. Cordingley, S. Kain); Geelong Hospital, Geelong, Victoria (R. Bell, R. McLennan); Mater Misericordiae Hospital, Newcastle, New South Wales (A. Enno); Prince of Wales Hospital, Sydney, New South Wales (S. Dunkley); Princess Alexandra Hospital, Brisbane, Queensland (P. Marlton, T. Mills); Royal North Shore Hospital, Sydney, New South Wales (C. Arthur); St. George Hospital, Sydney, New South Wales (A. Manoharan, T. Brighton, Y.L. Kwan); Westmead Hospital, Sydney, New South Wales (W. Benson, K. Bradstock, M. Hertzberg).

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Authors and Affiliations

  1. St. George Hospital, Kogarah, Sydney, New South Wales, 2217, Australia

    Arumugam Manoharan

  2. Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

    John Reynolds, Jane Matthews, Heather Baxter & Juliana Di Iulio

  3. Fremantle Hospital, Fremantle, Western Australia, Australia

    Michael Leahy

  4. Royal Melbourne Hospital, Melbourne, Victoria, Australia

    Surender Juneja

Authors
  1. Arumugam Manoharan
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  2. John Reynolds
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  3. Jane Matthews
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  4. Heather Baxter
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  5. Juliana Di Iulio
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  6. Michael Leahy
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  7. Surender Juneja
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Correspondence to Arumugam Manoharan.

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Manoharan, A., Reynolds, J., Matthews, J. et al. Flexible Low-Intensity Combination Chemotherapy for Elderly Patients with Acute Myeloid Leukaemia. Drugs Aging 24, 481–488 (2007). https://doi.org/10.2165/00002512-200724060-00004

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