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Phase I and pharmacokinetic study of Bay 38-3441, a camptothecin glycoconjugate, administered as a 30-minute infusion daily for five days every 3 weeks in patients with advanced solid malignancies

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Abstract

Bay 38-3441 is a camptothecin glycoconjugate which stabilizes the active lactone form of camptothecin and allows selective uptake into tumor cells. We conducted a phase I study of Bay 38-3441 administered as a 30-minute infusion daily for five consecutive days every 21 days. Thirty-one patients were enrolled at 8 dose levels. Most common nonhematologic side effects were diarrhea (29%), vomiting (19%), nausea (19%), lethargy (13%), and abdominal pain (10%). The main hematologic toxicity was prolonged neutropenia. Nine patients had a best response of stable disease with a median duration of 2.7 months (range: 2.3–20.6 months). The study was closed without reaching the maximum tolerated dose (MTD) due to excessive toxicity in a companion trial resulting in termination of development of this agent. Bay 38-3441 was well tolerated in this study with granulocytopenia as the main hematologic toxicity. This study showed that glycoconjugation is a feasible delivery technique for camptothecin.

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Authors and Affiliations

  1. National Cancer Institute of Canada, Clinical Trials Group, Kingston, Ontario, Canada

    Eric X. Chen (MD, PhD, FRCPC), Gerald Batist, Lillian L. Siu, Naeema Bangash, Martha Maclean, Lynn McIntosh, Wilson H. Miller Jr, Amit M. Oza & Lesley Seymour

  2. Bayer Inc, Toronto, Ontario, Canada

    Chetan Lathia & Oana Petrenciuc

  3. Department of Medical Oncology and Hematology, Princess Margaret Hospital, Room 5-221A, 610 University Ave., Toronto, Canada, M5G 2M9

    Eric X. Chen (MD, PhD, FRCPC)

Authors
  1. Eric X. Chen
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  2. Gerald Batist
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  3. Lillian L. Siu
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  4. Naeema Bangash
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  5. Martha Maclean
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  6. Lynn McIntosh
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  7. Wilson H. Miller Jr
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  8. Amit M. Oza
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  9. Chetan Lathia
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  10. Oana Petrenciuc
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  11. Lesley Seymour
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Corresponding author

Correspondence to Eric X. Chen.

Additional information

The study medication, Bay 43-9006 and a partial funding for the study were provided by Bayer Inc.

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Chen, E.X., Batist, G., Siu, L.L. et al. Phase I and pharmacokinetic study of Bay 38-3441, a camptothecin glycoconjugate, administered as a 30-minute infusion daily for five days every 3 weeks in patients with advanced solid malignancies. Invest New Drugs 23, 455–465 (2005). https://doi.org/10.1007/s10637-005-2905-1

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  • DOI: https://doi.org/10.1007/s10637-005-2905-1

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