A phase I open-label study of selinexor with paclitaxel and carboplatin in patients with advanced ovarian or endometrial cancers Journal Article
| Authors: | Rubinstein, M. M.; Grisham, R. N.; Cadoo, K.; Kyi, C.; Tew, W. P.; Friedman, C. F.; O'Cearbhaill, R. E.; Zamarin, D.; Zhou, Q.; Iasonos, A.; Nikolovski, I.; Xu, H.; Soldan, K. N.; Caird, I.; Martin, M.; Guillen, J.; Eid, K. T.; Aghajanian, C.; Makker, V. |
| Article Title: | A phase I open-label study of selinexor with paclitaxel and carboplatin in patients with advanced ovarian or endometrial cancers |
| 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 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. © 2020 Elsevier Inc. |
| Keywords: | paclitaxel; endometrial cancer; ovarian cancer; carboplatin; selinexor |
| Journal Title: | Gynecologic Oncology |
| Volume: | 160 |
| Issue: | 1 |
| ISSN: | 0090-8258 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2021-01-01 |
| Start Page: | 71 |
| End Page: | 76 |
| Language: | English |
| DOI: | 10.1016/j.ygyno.2020.10.019 |
| PUBMED: | 33139041 |
| PROVIDER: | scopus |
| PMCID: | PMC7779742 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2021 -- Source: Scopus |
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