Apatinib combined with oral etoposide in patients with platinum-resistant or platinum-refractory ovarian cancer (AEROC): a phase 2, single-arm, prospective study
| Autor: | Ying Xiong, Yan Ling Feng, Chun yan Lan, Min Zheng, Hui Qiang Huang, J. Li, Yan Na Zhang, Jing Xian Shen, Yan Fang Li, Xin Huang, Qing Liu, Yin Wang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult medicine.medical_specialty Time Factors Combination therapy Adolescent Pyridines Population Administration Oral Angiogenesis Inhibitors Platinum Compounds Drug Administration Schedule 03 medical and health sciences chemistry.chemical_compound Young Adult 0302 clinical medicine Internal medicine Antineoplastic Combined Chemotherapy Protocols Mucositis medicine Humans Apatinib Progression-free survival Prospective Studies Adverse effect Prospective cohort study education Aged Etoposide Ovarian Neoplasms education.field_of_study business.industry Middle Aged medicine.disease Progression-Free Survival 030104 developmental biology Oncology chemistry Response Evaluation Criteria in Solid Tumors Drug Resistance Neoplasm 030220 oncology & carcinogenesis Disease Progression Female business |
| Zdroj: | The Lancet. Oncology. 19(9) |
| ISSN: | 1474-5488 |
| Popis: | Summary Background Anti-angiogenic therapy combined with chemotherapy could improve the outcomes of patients with platinum-resistant ovarian cancer. Apatinib is an oral tyrosine kinase inhibitor that selectively inhibits VEGF receptor 2. We assessed the efficacy and safety of the combination therapy of apatinib and oral etoposide, considering the potential advantage of home administration without hospital admission, in patients with platinum-resistant or platinum-refractory ovarian cancer. Methods In this phase 2, single-arm, prospective study, we recruited patients aged 18–70 years with platinum-resistant or platinum-refractory ovarian cancer at the Sun Yat-sen University Cancer Center (China). The treatment consisted of apatinib at an initial dose of 500 mg once daily on a continuous basis, and oral etoposide at a dose of 50 mg once daily on days 1–14 of a 21-day cycle. Oral etoposide was administered for a maximum of six cycles. Treatment was continued until disease progression, patient withdrawal, or unacceptable toxic effects. The primary endpoint was the proportion of patients achieving an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1. We used Simon's two-stage design, and analysed efficacy in the intention-to-treat and per-protocol populations. Safety analyses included enrolled patients who had received at least one dose of study medication, but excluded those without any safety data. This study is registered with ClinicalTrials.gov , number NCT02867956 . Findings Between Aug 10, 2016, and Nov 9, 2017, we screened 38 and enrolled 35 patients. At the data cutoff date (Dec 31, 2017), 20 (57%) patients had discontinued the study, and 15 (43%) patients remained on treatment. Objective responses were achieved in 19 (54%; 95% CI 36·6–71·2) of 35 patients in the intention-to-treat population and in 19 (61%; 42·2–78·2) of 31 patients in the per-protocol population. The most common grade 3 or 4 adverse events were neutropenia (17 [50%]), fatigue (11 [32%]), anaemia (ten [29%]), and mucositis (eight [24%]). Serious adverse events were reported in two patients who were admitted to hospital (one patient had anaemia and anorexia; the other patient had increased ascites due to disease progression). No treatment-related deaths were recorded. Interpretation The combination of apatinib with oral etoposide shows promising efficacy and manageable toxicities in patients with platinum-resistant or platinum-refractory ovarian cancer, and further study in phase 3 trials is warranted. Funding None. |
| Databáze: | OpenAIRE |
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