A phase I open-label study of selinexor with paclitaxel and carboplatin in patients with advanced ovarian or endometrial cancers.
Gynecol Oncol
; 160(1): 71-76, 2021 01.
Article
em En
| MEDLINE
| ID: mdl-33139041
ABSTRACT
PURPOSE:
Selinexor, a selective inhibitor of nuclear export, monotherapy causes nuclear accumulation of tumor-suppressor proteins and has anti-tumor activity in ovarian and endometrial cancers. The safety and tolerability of oral selinexor plus intravenous carboplatin and paclitaxel chemotherapy (selinexor + CP) was evaluated in this population. PATIENTS ANDMETHODS:
This phase I, 3 + 3 dose-escalation study assessed 4 selinexor + CP regimens. Patients in cohorts of 3, regardless of disease type, were administered 1 of 4 alternating regimens (selinexor at 30 mg/m2 or 60 mg plus CP at AUC 5 and 175 mg/m2 or 80 mg/m2, respectively) for 6-10 cycles (1 cycle = 21 days), followed by selinexor maintenance. Enrolled patients with ovarian cancer had received 1 prior platinum-based therapy. Patients with endometrial cancer were chemotherapy-naive or had received 1 prior platinum-based therapy. Response was evaluated every 9 weeks.RESULTS:
Twenty-three patients were treated (5 serous ovarian cancer; 18 endometrial cancer, including 6 carcinosarcomas). The most common treatment-related adverse events (TRAEs) were thrombocytopenia (100%), leukopenia (91%), and hyperglycemia (87%). The most common grade 3/4 TRAEs were leukopenia (70%), neutropenia (70%), lymphopenia (61%), anemia (57%), and alanine transaminase increase (43%). One treatment-related dose-limiting toxicity (grade 3 syncope) occurred. Twelve patients achieved a partial response and 1 achieved a complete response. Responses to all four regimens were observed in ovarian and endometrial cancers.CONCLUSIONS:
Combination selinexor + CP was safe and tolerated in advanced ovarian and endometrial cancers.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Protocolos de Quimioterapia Combinada Antineoplásica
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Neoplasias do Endométrio
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article