caa a22 4500 465789617 CHVBK 20180323112019.0 cr unu---uuuuu 170327e19900801xx s 000 0 eng 10.1007/BF00171836 doi (NATIONALLICENCE)springer-10.1007/BF00171836 Phase I trial of intravenous vinzolidine (LY 104208) given on a biweekly dosing schedule [Elektronische Daten] [Daniel Budman, Willi Kreis, Joanne Behr, Philip Schulman, Stuart Lichtman, Steven Allen, Lora Weiselberg, W. Satterlee, Robert Nelson, Vincent Vinciguerra] Summary: Vinzolidine (VZL) is a semisynthetic vinca alkaloid with broad antitumor activity in animal models of malignancy but had unpredictable toxic effects when given orally to humans. To minimize the toxic effects due to potential erratic gastrointestinal absorption, this drug was restudied in man as an intravenous preparation given as a rapid injection every two weeks. The maximum tolerated dose (MTD) on this schedule was 9.0 mg/m2 with unpredictable leukopenia (usually occurring 5-14 days post treatment but appearing erratically), constipation, paralytic ileus, and inappropriate ADH syndrome as major toxicities. Nonhematologic toxicities were dose-limiting. Repetitive dosing at two week intervals was associated with leukopenia at D 14-15 in some but not all patients treated above 5.0 mg/m2 precluding further treatment on schedule. In contrast, the oral MTD of this agent in our prior studies was 45 mg/m2 with no evidence of delayed leukopenia. Intrapatient variability of toxicity was small; interpatient variability of toxicity was substantial and did not correlate with prior therapy. Because of the presence of delayed hematologic toxicity on repetitive dosing schedules, intravenous VZL should be given on a dosing schedule longer than 14 days. No antitumor activity was seen in this study. Kluwer Academic Publishers, 1990 vinzolidine nationallicence phase I nationallicence intravenous every 2 weeks nationallicence Budman Daniel Department of Medicine, North Shore University Hospital, Cornell Medical College, 11030, Manhasset, NY aut Kreis Willi Department of Medicine, North Shore University Hospital, Cornell Medical College, 11030, Manhasset, NY aut Behr Joanne Department of Medicine, North Shore University Hospital, Cornell Medical College, 11030, Manhasset, NY aut Schulman Philip Department of Medicine, North Shore University Hospital, Cornell Medical College, 11030, Manhasset, NY aut Lichtman Stuart Department of Medicine, North Shore University Hospital, Cornell Medical College, 11030, Manhasset, NY aut Allen Steven Department of Medicine, North Shore University Hospital, Cornell Medical College, 11030, Manhasset, NY aut Weiselberg Lora Department of Medicine, North Shore University Hospital, Cornell Medical College, 11030, Manhasset, NY aut Satterlee W. Eli Lilly Company, 46285, Indianapolis, IN, USA aut Nelson Robert Eli Lilly Company, 46285, Indianapolis, IN, USA aut Vinciguerra Vincent Department of Medicine, North Shore University Hospital, Cornell Medical College, 11030, Manhasset, NY aut Investigational New Drugs Kluwer Academic Publishers 8/3(1990-08-01), 269-274 0167-6997 8:3<269 1990 8 10637 https://doi.org/10.1007/BF00171836 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00171836 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Budman Daniel Department of Medicine, North Shore University Hospital, Cornell Medical College, 11030, Manhasset, NY aut NATIONALLICENCE 700 1- Kreis Willi Department of Medicine, North Shore University Hospital, Cornell Medical College, 11030, Manhasset, NY aut NATIONALLICENCE 700 1- Behr Joanne Department of Medicine, North Shore University Hospital, Cornell Medical College, 11030, Manhasset, NY aut NATIONALLICENCE 700 1- Schulman Philip Department of Medicine, North Shore University Hospital, Cornell Medical College, 11030, Manhasset, NY aut NATIONALLICENCE 700 1- Lichtman Stuart Department of Medicine, North Shore University Hospital, Cornell Medical College, 11030, Manhasset, NY aut NATIONALLICENCE 700 1- Allen Steven Department of Medicine, North Shore University Hospital, Cornell Medical College, 11030, Manhasset, NY aut NATIONALLICENCE 700 1- Weiselberg Lora Department of Medicine, North Shore University Hospital, Cornell Medical College, 11030, Manhasset, NY aut NATIONALLICENCE 700 1- Satterlee W. Eli Lilly Company, 46285, Indianapolis, IN, USA aut NATIONALLICENCE 700 1- Nelson Robert Eli Lilly Company, 46285, Indianapolis, IN, USA aut NATIONALLICENCE 700 1- Vinciguerra Vincent Department of Medicine, North Shore University Hospital, Cornell Medical College, 11030, Manhasset, NY aut NATIONALLICENCE 773 0- Investigational New Drugs Kluwer Academic Publishers 8/3(1990-08-01), 269-274 0167-6997 8:3<269 1990 8 10637 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer