Phase 1 study of alisertib (MLN8237) and weekly irinotecan in adults with advanced solid tumors.
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Azepines
/ therapeutic use
Cohort Studies
Drug Administration Schedule
Female
Humans
Irinotecan
/ therapeutic use
Male
Maximum Tolerated Dose
Middle Aged
Neoplasms
/ drug therapy
Protein Kinase Inhibitors
/ therapeutic use
Pyrimidines
/ therapeutic use
Young Adult
Alisertib
Aurora kinase A
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:
08 2021
08 2021
Historique:
received:
22
02
2021
accepted:
03
05
2021
pubmed:
17
5
2021
medline:
18
9
2021
entrez:
16
5
2021
Statut:
ppublish
Résumé
Aurora kinases are overexpressed or amplified in numerous malignancies. This study was designed to determine the safety and tolerability of the Aurora A kinase inhibitor alisertib (MLN8237) when combined with weekly irinotecan. In this single-center phase 1 study, adult patients with refractory advanced solid tumors received 100 mg/m A total of 17 patients enrolled at three dose levels. Dose-limiting toxicities included diarrhea, dehydration, and neutropenia. The MTD of alisertib combined with weekly irinotecan was 20 mg twice per day on days 1-3 and 8-10. One fatal cardiac arrest at the highest dose level tested was deemed possibly related to drug treatment. One partial response in 11 efficacy evaluable patients (9%) occurred in a patient with small cell lung cancer. The study was terminated prior to the planned expansion in patients with colorectal cancer. In contrast to prior results in a pediatric population, adult patients did not tolerate alisertib combined with irinotecan at clinically meaningful doses due to hematologic and gastrointestinal toxicities. The study was registered with ClinicalTrials.gov under study number NCT01923337 on Aug 15, 2013.
Identifiants
pubmed: 33993383
doi: 10.1007/s00280-021-04293-3
pii: 10.1007/s00280-021-04293-3
pmc: PMC8259450
mid: NIHMS1718857
doi:
Substances chimiques
Azepines
0
MLN 8237
0
Protein Kinase Inhibitors
0
Pyrimidines
0
Irinotecan
7673326042
Banques de données
ClinicalTrials.gov
['NCT01923337']
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
335-341Subventions
Organisme : NCI NIH HHS
ID : K12 CA138464
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA093373
Pays : United States
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