View in EDS

An EORTC-ECSG phase I study of LU 79553 administered every 21 or 42 days in patients with solid tumours.

Saved in:
Bibliographic Details
Title: An EORTC-ECSG phase I study of LU 79553 administered every 21 or 42 days in patients with solid tumours.
Authors: Awada, Ahmad, Thödtmann, R, Piccart-Gebhart, Martine, Wanders, Jantien, Schrijvers, A H G J, Von Broen, I-M, Hanauske, Axel-R, EORTC-ECSG phase I study
Source: European journal of cancer, 39 (6
Publication Year: 2003
Collection: DI-fusion : dépôt institutionnel de l'Université libre de Bruxelles (ULB)
Subject Terms: Sciences bio-médicales et agricoles, Adult, Aged, Amides -- administration & dosage, Amides -- adverse effects, Amides -- pharmacokinetics, Antineoplastic Agents -- administration & dosage, Antineoplastic Agents -- adverse effects, Antineoplastic Agents -- pharmacokinetics, Cohort Studies, Drug Administration Schedule, Female, Half-Life, Humans, Infusions, Intravenous, Isoquinolines -- administration & dosage, Isoquinolines -- adverse effects, Isoquinolines -- pharmacokinetics, Male, Maximum Tolerated Dose, Middle Aged, Neoplasms -- drug therapy
Description: A single-agent dose-escalating phase I and pharmacokinetic study on the naphthalamide agent, LU 79553, was performed to determine its safety profile, maximum tolerated dose (MTD) and recommended dose for phase II studies. LU 79553 was given intravenously (i.v.) every 3 weeks to patients with advanced solid cancers (an extended cohort of patients also received the drug every 6 weeks). 59 patients were enrolled into the study (50 patients in the 3-weekly schedule and 9 patients in the 6-weekly schedule). Dose levels studied ranged from 10 mg/m(2) to 160 mg/m(2). Neuro-muscular toxicity was identified as the dose-limiting toxicity (DLT). This muscular toxicity was observed after administrating total doses of 160-450 mg/m(2) (median 330 mg/m(2)). Non-DLTs consisted of diarrhoea, nausea and vomiting, fatigue and local venous phlebitis. The major haematological toxicities observed were anaemia and neutropenia (and were mainly observed at the two highest dose levels). The proposed dose for phase II studies using the 3-weekly regimen is 100 mg/m(2)/course (60 min infusion in 500 ml normal saline), but a close clinical follow-up of the patients for neuromuscular toxicity is mandatory. Prolongation of the treatment interval to 6 weeks, based upon the long half-life of the drug in the plasma and tissue, observed during this study, seemed not to be feasible in this heavily pretreated group of patients. ; Clinical Trial ; Clinical Trial, Phase I ; Journal Article ; info:eu-repo/semantics/published
Document Type: article in journal/newspaper
File Description: No full-text files
Language: English
Relation: uri/info:pii/S0959804902007761; uri/info:pmid/12651198
Availability: http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/53698
Accession Number: edsbas.C3639581
Database: BASE
Description
Abstract:A single-agent dose-escalating phase I and pharmacokinetic study on the naphthalamide agent, LU 79553, was performed to determine its safety profile, maximum tolerated dose (MTD) and recommended dose for phase II studies. LU 79553 was given intravenously (i.v.) every 3 weeks to patients with advanced solid cancers (an extended cohort of patients also received the drug every 6 weeks). 59 patients were enrolled into the study (50 patients in the 3-weekly schedule and 9 patients in the 6-weekly schedule). Dose levels studied ranged from 10 mg/m(2) to 160 mg/m(2). Neuro-muscular toxicity was identified as the dose-limiting toxicity (DLT). This muscular toxicity was observed after administrating total doses of 160-450 mg/m(2) (median 330 mg/m(2)). Non-DLTs consisted of diarrhoea, nausea and vomiting, fatigue and local venous phlebitis. The major haematological toxicities observed were anaemia and neutropenia (and were mainly observed at the two highest dose levels). The proposed dose for phase II studies using the 3-weekly regimen is 100 mg/m(2)/course (60 min infusion in 500 ml normal saline), but a close clinical follow-up of the patients for neuromuscular toxicity is mandatory. Prolongation of the treatment interval to 6 weeks, based upon the long half-life of the drug in the plasma and tissue, observed during this study, seemed not to be feasible in this heavily pretreated group of patients. ; Clinical Trial ; Clinical Trial, Phase I ; Journal Article ; info:eu-repo/semantics/published