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 Jr; Amit M Oza; Chetan Lathia; Oana Petrenciuc; Lesley Seymour

doi:10.1007/s10637-005-2905-1

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. 2005 Oct;23(5):455-65. doi: 10.1007/s10637-005-2905-1.

Authors

Eric X Chen¹, Gerald Batist, Lillian L Siu, Naeema Bangash, Martha Maclean, Lynn McIntosh, Wilson H Miller Jr, Amit M Oza, Chetan Lathia, Oana Petrenciuc, Lesley Seymour

Affiliation

¹ National Cancer Institute of Canada, Clinical Trials Group, Kingston, Ontario, Canada. [email protected]

PMID: 16133797
DOI: 10.1007/s10637-005-2905-1

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.

Publication types

Clinical Trial, Phase I
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Agranulocytosis / chemically induced
Antineoplastic Agents, Phytogenic / administration & dosage*
Antineoplastic Agents, Phytogenic / adverse effects
Antineoplastic Agents, Phytogenic / pharmacokinetics
Area Under Curve
Camptothecin / administration & dosage
Camptothecin / adverse effects
Camptothecin / analogs & derivatives*
Camptothecin / pharmacokinetics
Diarrhea / chemically induced
Dipeptides / administration & dosage*
Dipeptides / adverse effects
Dipeptides / pharmacokinetics
Drug Administration Schedule
Female
Glycoconjugates / administration & dosage
Glycoconjugates / adverse effects
Glycoconjugates / pharmacokinetics
Half-Life
Humans
Male
Middle Aged
Neoplasms / drug therapy*
Neoplasms / metabolism

Substances

20-O-(Nalpha-(4-(3-O-methylfucopyranosyloxy)phenylaminothiocarbonyl)histidylvalyl)camptothecin
Antineoplastic Agents, Phytogenic
Dipeptides
Glycoconjugates
Camptothecin