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
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
Externí odkaz: