A multicenter open-label randomized phase II trial of paclitaxel plus EP-100, a novel LHRH receptor-targeted, membrane-disrupting peptide, versus paclitaxel alone for refractory or recurrent ovarian cancer
| Autor: | Mary E. Gordinier, Alpa Nick, Anca Chelariu-Raicu, Carola Leuschner, John K. Whisnant, Linda M Bavisotto, Renata R. Urban, Robert L. Coleman, Graziela Zibetti Dal Molin |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Paclitaxel Lhrh receptor Recombinant Fusion Proteins Urology Phases of clinical research Peptide Ligands 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Refractory Antineoplastic Combined Chemotherapy Protocols medicine Humans Infusions Intravenous Adverse effect Aged Ovarian Neoplasms chemistry.chemical_classification Dose-Response Relationship Drug business.industry Cell Membrane Liver Neoplasms Obstetrics and Gynecology Middle Aged Peptide Fragments Progression-Free Survival 030104 developmental biology Oncology chemistry Drug Resistance Neoplasm Recurrent Ovarian Cancer 030220 oncology & carcinogenesis Female Neoplasm Recurrence Local Open label business Receptors LHRH Follow-Up Studies |
| Zdroj: | Gynecologic Oncology. 160:418-426 |
| ISSN: | 0090-8258 |
| DOI: | 10.1016/j.ygyno.2020.11.013 |
| Popis: | Objective This randomized open-label phase II study evaluated the safety and clinical activity of EP-100 plus weekly paclitaxel in patients with recurrent ovarian cancer expressing positive LHRH receptor. Methods In a limited “run-in” dose escalation phase for EP-100, six patients were treated with ascending dose levels (13 mg/m2, 20 mg/m2, 30 mg/m2). In the randomized phase, patients received weekly paclitaxel (80 mg/m2 intravenously) plus twice weekly EP-100 (30 mg/m2 intravenously; combination arm) or weekly paclitaxel alone (80 mg/m2 intravenously; paclitaxel arm). The primary study endpoint was overall response rate (ORR). Results Forty-four patients were then randomized to either the experimental combination arm (n = 23) or the standard of care paclitaxel monotherapy arm (n = 21). The ORR was 35% (95%CI 16%–57%) for the combination arm and 33% (95% CI 15%–57%) for the paclitaxel arm. An interesting observation from an unplanned analysis was that a subset of patients with target liver lesions showed a greater overall response rate to the combination (69%) compared to paclitaxel alone (16%). The frequency of treatment-related grade 3–4 adverse events was similar between treatment arms: 48% vs 43% for the combination and paclitaxel arms, respectively. Conclusions ORR in the EP-100 combination arm was similar to that in the group treated with paclitaxel alone; however, a subset of patients with liver metastases appeared to benefit from the combination. The addition of EP-100 did not appear to augment the adverse event profile of paclitaxel and was well tolerated. |
| Databáze: | OpenAIRE |
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