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Phase I dose escalation study of pegylated liposomal doxorubicin (Caelyx®) in combination with topotecan in patients with advanced malignancies

  • Phase I Studies
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Summary

Aims of this study were to determine the toxicity profile and the recommended dose of pegylated liposomal doxorubicin (Caelyx) in combination with topotecan in patients with advanced malignancies. Caelyx: 35 (DLI) or 40 (DLII) mg/m2/d1 was followed by 0.5 mg/m2/d topotecan daily for 5 days, every 4 weeks. Twenty-three patients received a total of 82 cycles. At DLII, 2/6 patients experienced dose-limiting toxicity consisting of grade 4 neutropenia lasting for more than 7 days and febrile neutropenia. At DLI, 4/18 and 2/18 patients presented febrile neutropenia and grade 4 sustained neutropenia, respectively. Non-hematological toxicities were mild to moderate. One patient with ovarian cancer presented a complete response. The hematological toxicity was a dose limiting factor that led to the recommended dose of 35 mg/m2 Caelyx on day 1 with 0.5 mg/m2/d topotecan on days 1–5. This study results suggest that alternative schedules of this combination are required.

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Authors and Affiliations

  1. Department of Medicine, Institut Gustave-Roussy, Villejuif

    Hervé Ghesquières, Sandrine Faivre, Patricia Pautier, Catherine Lhommé, Stéphanie Lozahic, Jean-Pierre Armand & Eric Raymond

  2. Shering-Plough Inc., Levallois Perret, France

    Latifa Djafari & Kamel Djazouli

  3. Department of Medical Oncology, Phase I Unit, Beaujon University Hospital, 100 Bd du Gal Leclerc, 92118, Clichy Cedex, France

    Sandrine Faivre

Authors
  1. Hervé Ghesquières
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  2. Sandrine Faivre
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  3. Latifa Djafari
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  4. Patricia Pautier
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  5. Catherine Lhommé
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  6. Stéphanie Lozahic
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  7. Kamel Djazouli
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  8. Jean-Pierre Armand
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  9. Eric Raymond
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Correspondence to Sandrine Faivre.

Additional information

Comment: Hervé Ghesquières and Sandrine Faivre contributed equally to this work and shall be regarded as joint first authors.Conflicts of interest: None of the authors declared conflicts of interest.

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Ghesquières, H., Faivre, S., Djafari, L. et al. Phase I dose escalation study of pegylated liposomal doxorubicin (Caelyx®) in combination with topotecan in patients with advanced malignancies. Invest New Drugs 24, 413–421 (2006). https://doi.org/10.1007/s10637-006-7520-2

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  • DOI: https://doi.org/10.1007/s10637-006-7520-2

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