A phase I open-label study of selinexor with paclitaxel and carboplatin in patients with advanced ovarian or endometrial cancers
| Autor: | Carol Aghajanian, Hongmei Xu, Rachel N. Grisham, Khalil T. Eid, Krysten Soldan, Claire F. Friedman, Alexia Iasonos, Imogen Caird, William P. Tew, Roisin E. O'Cearbhaill, Joyce Guillen, Qin Zhou, Maria M. Rubinstein, Dmitriy Zamarin, Chrisann Kyi, Vicky Makker, Ines Nikolovski, Karen Cadoo, Madhuri Martin |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Adult medicine.medical_specialty Paclitaxel medicine.medical_treatment Population Receptors Cytoplasmic and Nuclear Neutropenia Karyopherins Article Carboplatin 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans education Aged Ovarian Neoplasms Chemotherapy education.field_of_study Leukopenia Dose-Response Relationship Drug business.industry Endometrial cancer Obstetrics and Gynecology Middle Aged Triazoles medicine.disease Endometrial Neoplasms 030104 developmental biology Hydrazines chemistry Tolerability 030220 oncology & carcinogenesis Female medicine.symptom Ovarian cancer business |
| Zdroj: | Gynecol Oncol |
| ISSN: | 1095-6859 |
| Popis: | 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 and methods 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. |
| Databáze: | OpenAIRE |
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