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Phase I study using desferrioxamine and iron sorbitol citrate in an attempt to modulate the iron status of tumor cells to enhance doxorubicin activity

  • Original Articles
  • Desferrioxamine, Iron, Doxorubicin
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Summary

a novel approach to enhance the activity of doxorubicin is to increase the availability of cellular “chelatable” iron to participate in doxorubicin-mediated free-radical generation. To achieve this, we designed a regimen consisting of desferrioxamine (DFO, 50 mg/kg daily given as an i. v. infusion over 72 h) to increase cellular iron uptake. Thereafter, the combination of iron sorbitol citrate (ISC) and doxorubicin (as a single agent or as part of the CHOP regimen) was given. In a phase I study we investigated the toxicity of this regimen in nine patients with refractory malignant disease. Severe but reversible ocular toxicity (i. e., acute maculopathy) was observed in two patients. As these patients were the only ones who were pretreated with cisplatin, we caution against the use of DFO in cisplatin-pretreated patients. Severe phlebitis was encountered in five of nine patients. A partial remission was observed in two of four patients with refractory Non-Hodgkin's lymphoma who were treated with DFO, ISC, and doxorubicin as part of the CHOP regimen. We conclude that pretreatment with DFO and iron sorbitol citrate may be of benefit in the treatment of malignancies with doxorubicin-containing regimens, but ocular toxicity and severe phlebitis limits the use of DFO in this approach. The attachment of DFO to biocompatible polymers may be a method of overcoming the observed toxicity and warrants further study.

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Abbreviations

PR:

partial remission

PD:

progressive disease

OT:

ocular toxicity

Phl:

phlebitis of WHO grade>III

Dox:

doxorubicin dose given (whereas CHOP contains 50 mg/m2 doxorubicin)

AC:

adenocarcinoma

NHL:

Non-Hodgkin's lymphoma

SCLC:

small-cell lung cancer

CHOP:

cyclophosphamide/doxorubicin/vincristine/prednisone

COP:

cyclophosphamide/vincristine/prednisone

VP16/MTX/Cycl:

etoposide/methotrexate/cyclophosphamide

ProMACE-MOPP:

prednisone/methotrexate/Adriamycin/cyclophosphamide/etoposide/nitrogen mustard/vincristine/procarbazine/prednisone

FAM(TX):

5-fluorouracil/doxorubicin/mitomycin/methotrexate(TX)

CP:

cyclophosphamide/cisplatin

CDDP:

cisplatin

Mitox:

mitoxantrone

CDE:

cyclophosphamide/doxorubicin/etoposide

Chl:

chlorambucil

E/MTX/C:

etoposide/methotrexate/cyclophosphamide

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Authors and Affiliations

  1. Department of Internal Medicine, University Hospital Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands

    E. E. Voest, J. P. Neijt, B. S. van Asbeck & J. J. M. Marx

  2. Department of Ophthalmology, University Hospital Utrecht, Utrecht

    J. E. E. Keunen

  3. Department of Haematology, University Hospital Utrecht, Utrecht

    A. W. Dekker

  4. Department of Internal Medicine, Diakonessenhuis Utrecht, Utrecht

    J. W. R. Nortier

  5. Department of Ophthalmology, Diakonessenhuis Utrecht, Utrecht

    F. E. Ros

Authors
  1. E. E. Voest
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  2. J. P. Neijt
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  3. J. E. E. Keunen
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  4. A. W. Dekker
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  5. B. S. van Asbeck
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  6. J. W. R. Nortier
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  7. F. E. Ros
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  8. J. J. M. Marx
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Voest, E.E., Neijt, J.P., Keunen, J.E.E. et al. Phase I study using desferrioxamine and iron sorbitol citrate in an attempt to modulate the iron status of tumor cells to enhance doxorubicin activity. Cancer Chemother. Pharmacol. 31, 357–362 (1993). https://doi.org/10.1007/BF00686148

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  • DOI: https://doi.org/10.1007/BF00686148

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