title: 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.
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.
authors.affiliation: National Cancer Institute of Canada, Clinical Trials Group, Kingston, Ontario, Canada. eric.chen@uhn.on.ca
authors.forename: Eric X
authors.initials: EX
authors.lastname: Chen
authors.forename: Gerald
authors.initials: G
authors.lastname: Batist
authors.forename: Lillian L
authors.initials: LL
authors.lastname: Siu
authors.forename: Naeema
authors.initials: N
authors.lastname: Bangash
authors.forename: Martha
authors.initials: M
authors.lastname: Maclean
authors.forename: Lynn
authors.initials: L
authors.lastname: McIntosh
authors.forename: Wilson H
authors.initials: WH
authors.lastname: Miller
authors.forename: Amit M
authors.initials: AM
authors.lastname: Oza
authors.forename: Chetan
authors.initials: C
authors.lastname: Lathia
authors.forename: Oana
authors.initials: O
authors.lastname: Petrenciuc
authors.forename: Lesley
authors.initials: L
authors.lastname: Seymour
mesh_terms: D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D003967:Diarrhea / Q000139:chemically induced; D004151:Dipeptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D005260:Female; D006001:Glycoconjugates / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: C440617:20-O-(Nalpha-(4-(3-O-methylfucopyranosyloxy)phenylaminothiocarbonyl)histidylvalyl)camptothecin; D000972:Antineoplastic Agents, Phytogenic; D004151:Dipeptides; D006001:Glycoconjugates; D002166:Camptothecin