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.

Eric X Chen, Gerald Batist, Lillian L Siu, Naeema Bangash, Martha Maclean, Lynn McIntosh, Wilson H Miller, Amit M Oza, Chetan Lathia, Oana Petrenciuc, Lesley Seymour

National Cancer Institute of Canada, Clinical Trials Group, Kingston, Ontario, Canada. eric.chen@uhn.on.ca

Investigational new drugs 2005 Oct

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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.

Citation

Eric X Chen, Gerald Batist, Lillian L Siu, Naeema Bangash, Martha Maclean, Lynn McIntosh, Wilson H Miller, Amit M Oza, Chetan Lathia, Oana Petrenciuc, Lesley Seymour. 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. Investigational new drugs. 2005 Oct;23(5):455-65