A phase i study of ixazomib and erlotinib in patients with advanced solid tumors.
Invest New Drugs
; 40(1): 99-105, 2022 02.
Article
em En
| MEDLINE
| ID: mdl-34468905
ABSTRACT
BACKGROUND:
Preclinical studies have shown that the combined inhibition of EGFR and NF-kB pathways to target the RalB/TBK1 pathway led to synergistic antitumor activity. Based on this rationale, we conducted a Phase I dose-escalation study combining the EGFR inhibitor erlotinib with the NF-kB inhibitor ixazomib in advanced solid tumors. Patients and methods. Patients with advanced solid tumors were eligible. The bayesian optimal interval phase I dose escalation design was used to establish the maximum tolerated dose and recommended phase 2 dose (RP2D). Results. Nineteen patients with a range of solid tumors were enrolled. The most common treatment-related adverse events of any grade were diarrhea (42.1%, 8/19), followed by rash (36.8%, 7/19) and nausea (21.1%, 4/19). The combination RP2D for oral ixazomib was 4.0 mg on days 1, 8, and 15 of a 28-day cycle, with oral erlotinib 150 mg daily. While no patient achieved RECIST v1.1 objective responses, 3 patients with advanced sarcoma experienced durable RECIST v1.1 stable disease ≥ 6 months (8.4, 10.6, and 15.7 months) and the best response was -13% decrease in clear cell sarcoma. Conclusions. The combination of erlotinib and ixazomib was safe and well tolerated among patients with advanced cancer, with preliminary signals of antitumor activity in patients with advanced sarcoma.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Compostos de Boro
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Cloridrato de Erlotinib
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Glicina
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Neoplasias
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Antineoplásicos
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article