Back to Search
Start Over
A Phase I Study of a Combination of Liposomal Irinotecan and Veliparib in Solid Tumors.
- Source :
-
The oncologist [Oncologist] 2023 May 08; Vol. 28 (5), pp. 460-e298. - Publication Year :
- 2023
-
Abstract
- Background: Multiple preclinical studies have shown cytotoxic synergy involving combinations of poly (ADP-ribose) polymerase (PARP) inhibitors and topoisomerase 1 (TOP1) inhibitors, but such combinations have proven too toxic in clinical trials. Liposomal irinotecan (nal-IRI) achieved similar intratumoral exposure with better antitumor activity than the conventional TOP1 inhibitor irinotecan in preclinical models. Tumor targeted delivery of TOP1 inhibitor using nal-IRI and an intermittent schedule of administration of PARP inhibitor may provide a tolerable combination.<br />Methods: A phase I study was performed to evaluate the safety and tolerability of escalating doses of nal-IRI and the PARP inhibitor veliparib in patients with solid tumors resistant to standard treatments. Nal-IRI was administered on days 1 and 15 and veliparib on days 5-12 and 19-25 in 28-day cycles.<br />Results: Eighteen patients were enrolled across 3 dose levels. Five patients encountered dose-limiting toxicities, including grade 3 diarrhea lasting more than 72 h in 3 patients and 1 patient each with grade 4 diarrhea and grade 3 hyponatremia. The most common grade 3 or 4 toxicities included diarrhea (50% of patients), nausea (16.6%), anorexia, and vomiting (11.1% each) (Table 1). There was no difference in frequencies of adverse events based on UGT1A1*28 status or prior opioid use (Table 1).<br />Conclusion: The clinical trial was terminated due to high frequency of unacceptable gastrointestinal toxicities, which precluded dose escalation of veliparib in combination with nal-IRI (ClinicalTrials.gov Identifier: NCT02631733).<br /> (Published by Oxford University Press 2023.)
- Subjects :
- Humans
Irinotecan pharmacology
Irinotecan therapeutic use
Poly(ADP-ribose) Polymerase Inhibitors adverse effects
Topoisomerase I Inhibitors adverse effects
Poly(ADP-ribose) Polymerases
Diarrhea chemically induced
Antineoplastic Combined Chemotherapy Protocols adverse effects
Neoplasms drug therapy
Neoplasms pathology
Antineoplastic Agents therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1549-490X
- Volume :
- 28
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The oncologist
- Publication Type :
- Academic Journal
- Accession number :
- 37010988
- Full Text :
- https://doi.org/10.1093/oncolo/oyad023