Oral administration of irinotecan in patients with solid tumors: an open-label, phase I, dose escalating study evaluating safety, tolerability and pharmacokinetics.
Administration, Oral
Aged
Aged, 80 and over
Cohort Studies
Drug Administration Schedule
Female
Follow-Up Studies
Glucuronosyltransferase
/ metabolism
Humans
Irinotecan
/ pharmacokinetics
Male
Maximum Tolerated Dose
Middle Aged
Neoplasms
/ drug therapy
Prognosis
Tissue Distribution
Topoisomerase I Inhibitors
/ pharmacokinetics
Dose finding
Oral irinotecan
Phase I
Journal
Cancer chemotherapy and pharmacology
ISSN: 1432-0843
Titre abrégé: Cancer Chemother Pharmacol
Pays: Germany
ID NLM: 7806519
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
20
07
2018
accepted:
31
10
2018
pubmed:
9
11
2018
medline:
13
11
2019
entrez:
9
11
2018
Statut:
ppublish
Résumé
Oral drug formulations have several advantages compared to intravenous formulation. Apart from patient convenience and favorable pharmacoeconomics, they offer the possibility of frequent drug administration at home. In this study, we present a new oral irinotecan formulation designed as an enteric coated immediate release tablet which in pre-clinical studies has shown good exposure with low variability. A phase I, dose escalating study to assess safety, tolerability, pharmacokinetics and efficacy of an oral irinotecan formulation and to establish the maximum tolerated dose (MTD). Each treatment cycle was once-daily irinotecan for 14 days followed by 1 week rest. 25 patients were included across four cohorts; 3 patients were included in cohort 1 (20 mg/m Oral irinotecan was generally well tolerated; side effects were manageable and similar in type to those observed with intravenous irinotecan. Hematological toxicities were few and only grade 1/2. In this heavily pre-treated patient population, oral irinotecan demonstrated activity even among patients previously treated with irinotecan.
Sections du résumé
BACKGROUND
Oral drug formulations have several advantages compared to intravenous formulation. Apart from patient convenience and favorable pharmacoeconomics, they offer the possibility of frequent drug administration at home. In this study, we present a new oral irinotecan formulation designed as an enteric coated immediate release tablet which in pre-clinical studies has shown good exposure with low variability.
METHODS
A phase I, dose escalating study to assess safety, tolerability, pharmacokinetics and efficacy of an oral irinotecan formulation and to establish the maximum tolerated dose (MTD). Each treatment cycle was once-daily irinotecan for 14 days followed by 1 week rest.
RESULTS
25 patients were included across four cohorts; 3 patients were included in cohort 1 (20 mg/m
CONCLUSIONS
Oral irinotecan was generally well tolerated; side effects were manageable and similar in type to those observed with intravenous irinotecan. Hematological toxicities were few and only grade 1/2. In this heavily pre-treated patient population, oral irinotecan demonstrated activity even among patients previously treated with irinotecan.
Identifiants
pubmed: 30406838
doi: 10.1007/s00280-018-3720-7
pii: 10.1007/s00280-018-3720-7
pmc: PMC6373187
doi:
Substances chimiques
Topoisomerase I Inhibitors
0
Irinotecan
7673326042
UGT1A1 enzyme
EC 2.4.1.-
Glucuronosyltransferase
EC 2.4.1.17
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
169-178Références
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