apatinib and Carcinoma--Non-Small-Cell-Lung

To investigate the efficacy and safety of apatinib alone or apatinib plus paclitaxel/docetaxel versus paclitaxel/docetaxel in the treatment of advanced non-small cell lung cancer (NSCLC) through pooling of open published data.. The electronic databases of Medline (1960-2021.5), Cochrane central register of controlled trials (CENTRAL), EMBASE(1980-2021.5) and Wan fang (1986-2021.5) were systematically searched by two reviewers to identify the relevant clinical trials related to the above subject. The objective response rate (ORR), disease control rate (DCR) and drug relevant adverse reactions were pooled and demonstrated by risk ratio (RR) and 95% confidence interval (95% CI). The statistical heterogeneity across studies was assessed by I-square test. The publication bias was evaluated by Egger's line regression test and demonstrated by Begg's funnel plot.. Apatinib alone or apatinib plus paclitaxel/docetaxel was superior to paclitaxel/docetaxel for ORR and DCR. However, combined treatment with apatinib appears to increase the risk of a patient developing an adverse reaction, especially hypertension and hand-foot syndrome.

Topics: Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Docetaxel; Humans; Lung Neoplasms; Paclitaxel; Protein Kinase Inhibitors; Pyridines

Pulmonary sarcomatoid carcinoma (PSC) is an uncommon type of non-small cell lung cancer, exhibiting aggressive behavior and resistance to the conventional chemoradiotherapy. To date, the optimal treatment for PSC has not been elucidated.. Three male patients including a 69-year-old smoker (Case 1), a 45-year-old non-smoker (Case 2), and a 69-year-old smoker (Case 3) were admitted because of cough, back pain, and loss of body weight respectively.. Radiographical examinations in these patients showed bulky intrathoracic lesions, which were pathologically diagnosed as PSC staging III-IV by computed tomography-guided percutaneous biopsy and endoscopy.. Immunotherapy was not covered by their health insurance and they refused immune checkpoint inhibitors for financial reasons. In addition, a radical resection was not appropriate due to the advanced staging of these lesions. Therefore, first-line albumin-bound paclitaxel (nab-paclitaxel, 260 mg/m of the body surface area) and carboplatin (area under curve 5) combined with oral apatinib (425 mg, daily) were administered empirically.. Two patients achieved a partial response and the other case showed stable disease lasting for more than 6 months. However, 1 of them indicated progression on the 7-month follow up.. Nab-paclitaxel/carboplatin plus apatinib showed limited short-term efficacy in advanced, unresectable PSC. The rapid resistance of PSC to the current therapeutic regimen necessitates further researches, as more effective agents are urgently needed.

Topics: Aged; Albumins; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Carboplatin; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Male; Middle Aged; Non-Smokers; Paclitaxel; Pyridines; Smokers; Tomography, X-Ray Computed

Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Odds Ratio; Progression-Free Survival; Proportional Hazards Models; Pyridines; Randomized Controlled Trials as Topic; Treatment Outcome

Although targeted therapy directed toward driver mutations has produced a significant efficacy benefit for patients with non-small cell lung cancer (NSCLC), many patients do not possess mutations associated with the approved targeted drugs. Angiogenic agents play an important role in the therapeutic strategy for advanced NSCLC. Apatinib is a novel tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor-2. A phase II clinical trial demonstrated the survival benefit of apatinib monotherapy in advanced NSCLC. Moreover, addition of anti-angiogenic agents to chemotherapy showed robust efficacy in advanced NSCLC, regardless of tumor histology. Here, we present the case of a heavily pretreated lung adenocarcinoma patient who was treated with apatinib and apatinib continuation plus docetaxel re-challenge. He was negative for several driver genes, including EGFR, ALK, KRAS, ROS1, HER2, RET and BRAF. The previous treatment included platinum-based doublets, pemetrexed monotherapy, docetaxel plus bevacizumab, gefitinib monotherapy, nab-paclitaxel monotherapy, irinotecan plus oxaliplatin and radiotherapy. He obtained a partial response after both apatinib monotherapy and apatinib plus docetaxel treatment, with progression-free survival durations of 5 months and 6 months, respectively. This case indicated that apatinib monotherapy or apatinib plus docetaxel might be regarded as a therapeutic option for heavily pretreated patients with advanced non-squamous NSCLC.

Topics: Adenocarcinoma of Lung; Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Carcinoma, Non-Small-Cell Lung; Docetaxel; Humans; Lung; Lung Neoplasms; Male; Neoplasm Staging; Pyridines; Tomography, X-Ray Computed; Treatment Outcome

Non-small cell lung cancer is one of the most commom malignant tumor being harmful to people's life and health. Most of the patients have developed to the last stage which not suitable for surgical indications, so radiation and chemotherapy is the main treatment strategy. In recent years, with the theory of anti-angiogenesis therapy for malignant tumors, apatinib as a promising novel medicine to treat malignant tumors, represents synergistic antitumor effects in combination with radiotherapy. The underlying mechanisms may include make blood vessel normalization, alleviating inner hypoxia, and angiogenic factors regulation. Apatinib in combination with radiotherapy may become a new and effective treatment strategy of non-small cell lung cancer.. 非小细胞肺癌是危害人类生命健康的最常见的恶性肿瘤之一。大多数患者确诊时为晚期，不符合手术适应症，主要的治疗方法是放化疗联合。近年来，随着抗血管生成治疗恶性肿瘤理论的提出，阿帕替尼作为一种新型的抗肿瘤药物，与放疗联合具有协同作用。可能的机制包括使血管正常化，改善肿瘤内乏氧情况，调节促血管生成因子水平等。将阿帕替尼与放疗联合有望成为一种新的治疗策略应用于非小细胞肺癌的治疗中，提高肺癌的治疗效果。.

Topics: Animals; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Humans; Lung Neoplasms; Pyridines

Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has been proved to be effective and safe in treating heavily pretreated patients with gastric cancer.The aim of the study was to explore the use of apatinib in treatment of nonsmall cell lung cancer and its side effects.We report 2 patients presented with advanced nonsmall-cell lung cancer, who received apatinib after failure in the first- or third-line chemotherapy. They are treated with apatinib in daily dose of 850 mg, 28 days per cycle.Favorable oncologic outcomes were achieved in the 2 cases after the treatment of apatinib. Patient I's progression-free-survival has increased to 4.6 months after palliative therapy of apatinib, whereas Patient II nearly 6 months. The common side effects of apatinib were hypertension and hand-foot syndrome; however, the toxicity of apatinib was controllable and tolerable.Apatinib may be an option for advanced nonsmall cell lung cancer after failure of chemotherapy or other targeted therapy. But that still warrants further investigation in the prospective study.

Topics: Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Hand-Foot Syndrome; Humans; Hypertension; Lung Neoplasms; Male; Middle Aged; Pyridines; Retreatment

Camrelizumab (an anti-programmed cell death protein-1 antibody) combined with apatinib (an antiangiogenic agent) has conferred benefits for advanced NSCLC. We aimed to assess the activity and safety of neoadjuvant camrelizumab plus apatinib in patients with resectable NSCLC.. In this phase 2 trial, patients with histologically confirmed resectable stages IIA to IIIB NSCLC (stage IIIB, T3N2 only) received intravenous camrelizumab (200 mg) every 2 weeks for three cycles and oral apatinib (250 mg) once daily for 5 days followed by 2 days off for 6 weeks. Surgery was planned 3 to 4 weeks after apatinib discontinuation. The primary end point was major pathologic response (MPR) rate, assessed in patients who received at least one dose of neoadjuvant treatment and underwent surgery.. Between November 9, 2020, and February 16, 2022, 78 patients were treated and 65 (83%) underwent surgery. All 65 patients achieved an R0 surgical resection. Among the 65 patients, 37 (57%, 95% confidence interval [CI]: 44%-69%) had an MPR, of whom 15 (23%, 95% CI: 14%-35%) had a pathologic complete response (pCR). Pathologic responses observed in squamous cell NSCLC were superior to adenocarcinoma (MPR: 64% versus 25%; pCR: 28% versus 0%). The radiographic objective response rate was 52% (95% CI: 40%-65%). Among all the 78 enrolled patients, 37 (47%, 95% CI: 36%-59%) had an MPR, of whom 15 (19%, 95% CI: 11%-30%) had a pCR. Four (5%) of 78 patients had grade 3 neoadjuvant treatment-related adverse events. No grade 4 or 5 treatment-related adverse events occurred. Receiver operating characteristic analysis revealed a significant correlation between the maximum reduction of standard uptake values and pathologic response (R = 0.619, p < 0.0001). In addition, baseline programmed death-ligand 1 expression, HOXA9 and SEPT9 methylation levels, and circulating tumor DNA status before surgery were associated with pathologic responses.. Neoadjuvant camrelizumab plus apatinib was found to have promising activity and manageable toxicity in patients with resectable stages IIA to IIIB NSCLC, which might be a potential therapeutic option in neoadjuvant setting.

Topics: Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Neoadjuvant Therapy

Although targeted agents have been gradually applied in the treatment of HER2-mutated non-small cell lung cancer (NSCLC) in recent years, patients' therapeutic demands are far from being met. PATHER2 was the first phase 2 trial to explore the efficacy and safety of the HER2-targeted tyrosine kinase inhibitor (TKI) pyrotinib plus the antiangiogenic agent apatinib in previously treated HER2-altered metastatic NSCLC patients.. HER2-mutated or HER2-amplified metastatic NSCLC patients who had failed at least first-line chemotherapy or HER2-targeted TKIs received oral pyrotinib 400 mg plus apatinib 250 mg once daily until disease progression, intolerable toxicity, or death. The primary endpoint was the investigator-assessed objective response rate (ORR).. Between March 2019 and December 2020, 33 patients were enrolled; 13 (39.4%) presented brain metastases, and 16 (48.5%) had received at least two lines of prior chemotherapy or HER2-targeted TKIs. As of September 20, 2021, the median follow-up duration was 11.3 (range, 3.5-26.0) months. The investigator-assessed ORR was 51.5% (17/33; 95% CI, 33.5 to 69.2%), and the disease control rate was 93.9% (31/33; 95% CI, 79.8 to 99.3%). The median duration of response, progression-free survival, and overall survival were 6.0 (95% CI, 4.4 to 8.6) months, 6.9 (95% CI, 5.8 to 8.5) months, and 14.8 (95% CI, 10.4 to 23.8) months, respectively. The most frequent grade ≥ 3 treatment-related adverse events included diarrhea (3.0%) and hypertension (9.1%). No treatment-related deaths were reported.. Pyrotinib plus apatinib demonstrated promising antitumor activity and a manageable safety profile in HER2-mutated or HER2-amplified metastatic NSCLC patients.. Chinese Clinical Trial Registry Identifier: ChiCTR1900021684 .

Topics: Acrylamides; Aminoquinolines; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Prospective Studies; Pyridines

Brain radiotherapy (BR) is a well-recognized approach for multiple brain metastases (BMs) from non-small-cell lung cancer (NSCLC). However, the prognosis for these patients remains poor. Apatinib, an antiangiogenic agent targeting vascular endothelial growth factor receptor-2, has shown excellent efficacy in multiple solid tumors. This phase II (WWW. ClinicalTrials.gov Identifier: VEGFR-2 NCT03801200) randomized trial aims to evaluate the efficacy and safety of this combined modality paradigm in patients with BMs from driver mutation-negative NSCLC. This is a multicenter, open-label, randomized controlled clinical trial. A total of 90 eligible patients will be allocated in a 1:1 ratio, to either the experimental group (concurrent apatinib and BR) or the control group (BR alone). The primary endpoint is intracranial progression-free survival. The secondary endpoints include intracranial objective response rate, intracranial disease control rate, intracranial time to progression, overall survival, and occurrence of peritumoral brain edema using standardized measurement. Quality of life and adverse events will also be evaluated. Assessments will be carried out before enrollment (baseline) along with 4 and 12 weeks after radiotherapy, followed by every 12 weeks thereafter and up to 24 months. In summary, the aim of this trial is to demonstrate the clinical efficacy and safety of concurrent BR and apatinib in patients with driver mutation-negative NSCLC with multiple BMs, in efforts to expand management options for this population with poor prognosis.

Topics: Antineoplastic Agents; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cranial Irradiation; Humans; Lung Neoplasms; Mutation; Progression-Free Survival; Protein Kinase Inhibitors; Pyridines; Quality of Life; Vascular Endothelial Growth Factor Receptor-2

Our preclinical work suggests that appropriate angiogenesis inhibition could potentiate PD-1/PD-L1 blockade via alleviating hypoxia, increasing infiltration of CD8. The study included phase Ib apatinib dose-escalation and phase II expansion cohorts. Patients received apatinib at doses of 250-500 mg orally once daily, in combination with camrelizumab 200 mg intravenously every 2 weeks.. Combined apatinib and camrelizumab showed encouraging antitumor activity and acceptable toxicity in chemotherapy-pretreated patients with advanced nonsquamous NSCLC. Patients with STK11/KEAP1 mutation might derive more benefits from this combination. We will validate these results in an ongoing phase III trial (NCT04203485).

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Case-Control Studies; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Prognosis; Pyridines; Retrospective Studies; Survival Rate; Young Adult

For advanced nonsquamous non-small cell lung cancer (NSCLC), the mechanisms of resistance to first-line immunotherapy are not clear. Immune checkpoint inhibitors (ICIs) in combination with agents targeting other pathways may serve as second-line therapy options. Apatinib (a vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor) could increase the efficacy of camrelizumab (an ICI agent). The efficacy and safety of this combination regimen as a second-line therapy for NSCLC patients after failure on first-line immunotherapy has not previously been evaluated.. In this single-arm, multicenter, phase II trial, metastatic nonsquamous NSCLC patients previously treated with single-agent ICI or ICI plus chemotherapy will be enrolled. Participants will receive intravenous camrelizumab 200 mg D1 and oral apatinib 250 mg D1-21 for a 21-day cycle. The study treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint is progression-free survival by investigator. Secondary endpoints are overall survival, objective response rate, disease control rate, duration of response by investigator, quality of life, safety, and toxicity.. This trial will provide evidence of the benefit of treatment with camrelizumab combined with apatinib in advanced nonsquamous NSCLC patients who were previously treated with first-line immunotherapy.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Drug Therapy, Combination; Humans; Immunotherapy; Lung Neoplasms; Middle Aged; Progression-Free Survival; Pyridines; Quality of Life; Young Adult

This clinical trial (ChiCTR1800019185) is designed to be an open-label, prospective, single-center, single arm exploratory research study. The study will recruit non-small cell lung cancer patients (NSCLC) with slow progression after first-line treatment with EGFR-TKI drugs. Slow progression will be confirmed by the presence of serum carcinoembryonic antigen or imaging evaluation. The primary aim is to assess progression-free survival after EGFR-TKIs treatment combined with apatinib 250 mg once daily. The secondary objectives are to evaluate objective efficacy, disease control rates, quality of life, overall survival, and safety. From September 2018 to September 2020, under specific entry and discharge standards, we plan to enroll 38 eligible patients until the end of the study. We hope that our study will help to explore a new way of combining the small molecular inhibitors of antiangiogenesis with EGFR-TKIs to overcome acquired drug resistance.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Crown Ethers; Disease Progression; Drug Resistance, Neoplasm; ErbB Receptors; Erlotinib Hydrochloride; Female; Follow-Up Studies; Gefitinib; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Prognosis; Prospective Studies; Pyridines; Quinazolines; Research Design; Young Adult

There is currently no standard treatment strategy for patients with advanced non-small cell lung cancer (NSCLC) without driver gene variation after failure of 2 or more lines of chemotherapy.. To assess the efficacy and safety of apatinib combined with oral vinorelbine.. This phase 2 prospective nonrandomized clinical trial evaluating the efficacy and safety of apatinib plus vinorelbine recruited patients from Hunan Cancer Center, Hunan, China, from January 1, 2017, to November 30, 2018. Eligible patients were those with wild-type advanced NSCLC whose disease did not respond to at least 2 lines of chemotherapy. Patients were evaluated until December 31, 2019. Data were analyzed from July 2019 to December 2019.. Apatinib at an initial dose of 500 mg once daily and oral vinorelbine 60 mg/m2 once weekly were administered until disease progression, patient withdrawal, or occurrence of unacceptable toxic effects.. The primary end point was overall response rate. Secondary end points were overall survival, progression-free survival, and safety.. The potential efficacy of apatinib plus vinorelbine was identified using drug susceptibility assay based on 3-dimensional coculture of tumor cells derived from 3 patients with lung adenocarcinoma. Among 30 patients enrolled, the median (range) age was 63 (34-78) years and 18 (60%) were men. Most patients (27 patients [90%]) had stage IV disease, and the median (range) number of prior unsuccessful treatments was 2 (2-5) lines of chemotherapy. Twenty-five patients (83%) completed the treatment, while 5 patients (17%) discontinued treatment owing to intolerable adverse events. The overall response rate was 36.7% (11 patients) and the disease control rate was 76.7% (23 patients). The median progression-free survival was 4.5 (95% CI, 2.4-6.6) months, and the median overall survival was 10.0 (95% CI, 4.8-17.1) months. Hand-foot syndrome was the most common adverse event observed, including grade 3 hand-foot syndrome observed in 5 patients (17%) and grade 4 hand-foot observed in 1 patient (3%). Grade 3 weakness was observed in 1 patient (3%).. These findings suggest that apatinib combined with oral vinorelbine is a potentially effective regimen with an acceptable safety profile. This regimen may have potential as a treatment option for patients with wild-type advanced NSCLC whose disease failed at least 2 prior lines of chemotherapy.. ClinicalTrials.gov Identifier: NCT03652857.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Middle Aged; Progression-Free Survival; Prospective Studies; Pyridines; Treatment Outcome; Vinorelbine

The efficacy of second-line treatment for advanced non-small cell lung carcinoma (NSCLC) without a sensitizing driver gene mutation is still unsatisfactory. The combination of apatinib and chemotherapy improved progression-free survival in the second-line therapy of advanced NSCLC without a sensitizing mutation. This study offers a new treatment strategy for second-line treatment of such patients but requires confirmation in a larger multi-institutional trial.. This study explored the efficacy and safety of apatinib combined with single-agent chemotherapy versus single-agent chemotherapy in the second-line treatment of advanced non-small-cell lung carcinoma (NSCLC) without driver mutations.. In this double-arm, open label, exploratory clinical study, we enrolled patients with unresectable locally advanced or advanced NSCLC without driver mutations that had progressed following first-line chemotherapy. The subjects were allocated into an experimental group and a control group by 2:1. The experimental group received apatinib combined with four cycles of docetaxel or pemetrexed until disease progression, intolerable toxicity, or discontinuation at the patient' request. The control group only received four cycles of docetaxel or pemetrexed. The primary endpoints were progression-free survival (PFS), and the secondary endpoints were overall survival (OS), disease control rate (DCR), and safety.. Thirty-seven patients were enrolled. The efficacy of 33 patients was evaluated. The median PFS was 5.47 versus 2.97 months, the DCR was 95% versus 73%, and the objective response rate (ORR) was 27% versus 9% in the experimental versus control group. The OS was still under follow-up. The most common adverse effects included hypertension, hand-foot skin reaction (HFSR), and fatigue.. Apatinib combined with single-agent chemotherapy may be a novel option for second-line treatment of advanced NSCLC.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pemetrexed; Pyridines

Topics: Aged; Anaplastic Lymphoma Kinase; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Female; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Neoplasm Staging; Pemetrexed; Pyridines; Treatment Outcome

Gefitinib, as the first epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC), has been proved to significantly improve the progression-free survival (PFS) in the first-line setting but suffers from resistance 7-10 months after treatment initiation. Apatinib (YN968D1), a potent vascular endothelial growth factor receptor (VEGFR) 2-TKI, specifically binds to VEGFR2 and leads to anti-angiogenetic and anti-neoplastic effect. Concurrent inhibition of VEGFR and EGFR pathways represents a rational approach to improve treatment responses and delay the onset of treatment resistance in EGFR-mutant NSCLC. This ACTIVE study aims to assess the combination of apatinib and gefitinib as a new treatment approach for EGFR-mutant NSCLC as a first-line setting.. This multicenter, randomized, double-blind, placebo-controlled phase III study (NCT02824458) has been designed to assess the efficacy and safety of apatinib or placebo combined with gefitinib as a first-line treatment for patients with EGFR-mutant advanced NSCLC. A total of 310 patients with EGFR-mutation (19del or 21L858R), pathological stage IIIB to IV non-squamous NSCLC were to be enrolled. The primary endpoint is investigator assessment of PFS, and the secondary endpoints include independent radiological central (IRC)-confirmed PFS, overall survival (OS), objective response rate (ORR), disease control rate (DCR), time to progressive disease (TTPD), duration of response (DoR), quality of life (QoL) and safety. The patients are randomized in a 1:1 ratio to receive gefitinib (250 mg, p.o. q.d.) plus apatinib (500 mg, p.o. q.d.) or gefitinib plus placebo, given until disease progression or intolerable adverse events. Exploratory biomarker analysis will be performed. This study is being conducted across China and comprises of 30 participating centers. Enrollment commenced in August 2017 and finished in December 2018, most of the patients are in the follow-up period.. The present study will be the first to evaluate the efficacy and safety profile of the combination of apatinib plus gefitinib as a first-line therapy for patients with EGFR-positive advanced non-squamous NSCLC. Importantly, this trial will provide comprehensive evidence on the treatment of EGFR-TKIs combined with antiangiogenic therapy. Trial registration Clinicaltrials.gov NCT02824458. Registered 23 June 2016.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Clinical Trials, Phase III as Topic; Double-Blind Method; ErbB Receptors; Gefitinib; Humans; Lung Neoplasms; Multicenter Studies as Topic; Mutation; Protein Kinase Inhibitors; Pyridines; Randomized Controlled Trials as Topic

Apatinib is an oral small-molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR-2). Some clinical trials have demonstrated that apatinib is efficacious against advanced nonsquamous NSCLC.. This study aimed to probe efficacy and safety of apatinib plus docetaxel, as the second or above line treatment, in advanced nonsquamous NSCLC.. Multicenter, prospective, single arm study.. Three teaching hospitals centers in the Sichuan.. Fourteen patients with stage IVA/B nonsquamous NSCLC had previously received at least 1 platinum-based chemotherapy regimen.. Patients who were enrolled between November 2016 and January 2018 were given docetaxel (75 mg/m, i.v., d1) plus oral apatinib (250 mg/d), 4 weeks as one cycle, until disease progression or intolerance to adverse events (AE).. The primary endpoint was progression-free survival (PFS). The secondary endpoints comprised objective response rate (ORR), disease control rate (DCR), overall survival (OS), and AE incidence rate.. All patients carried adenocarcinoma by pathological type. The median follow-up duration was 9.76 months. Out of 14 cases, 12 were evaluable, showing ORR of 33.33%, DCR of 66.67%, DCR of 50% in cases with brain metastasis, median PFS of 2.92 months (95% CI: 1.38-4.48), and 6-month OS of 80%. Primary AEs encompassed: leukopenia in 7 cases (58.33%), hand-foot skin reaction in 5 cases (41.67%), and diarrhea in 4 cases (33.33%). Among them, grade 3 AEs were: leukopenia in 4 cases (33.33%), and hand-foot skin reaction in 1 case (8.33%). No grade 4/5 AEs were reported. Univariate and multivariate analysis were conducted respectively for PFS and OS. These factors encompassed: gender, age, gene mutations, clinical stage, ECOG scores, quantity of metastatic foci, brain metastasis, and hand-foot skin reaction. Results demonstrated zero risk factors for PFS or OS.. Apatinib plus docetaxel, as the second or above line treatment, is effective and safe against advanced nonsquamous NSCLC, with good tolerance profile.. NCT03416231.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Disease Progression; Docetaxel; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Preliminary Data; Prospective Studies; Protein Kinase Inhibitors; Pyridines; Retreatment; Survival Analysis; Treatment Outcome; Tubulin Modulators

Apatinib exhibits broad-spectrum antitumor activities by selectively inhibiting vascular endothelial growth factor receptor-2. This study evaluated the efficacy and safety of apatinib in patients with advanced non-squamous non-small-cell lung cancer who were heavily pretreated or not suitable to receive standard second-line chemotherapy.. This was an open-label, single-arm phase II clinical trial (ClinicalTrials.govNCT02515435). Patients received 500 or 750 mg apatinib daily until progression, unacceptable toxicity, withdrawal, or death. The primary endpoint was the objective response rate. The secondary endpoints included disease control rate, progression-free survival, overall survival, and side effects. Apatinib administration was allowed beyond disease progression.. Between March 2015 and August 2016, 40 patients were enrolled. Among them, 6 (15.0%), 16 (40.0%), and 18 (45.0%) received apatinib as the second-, third-, and fourth-line or beyond treatment, respectively. The mean dosage of apatinib was 477.0 ± 85.3 mg/day. Thirty-eight patients were available for response evaluation; the objective response rate and disease control rate were 13.2% and 63.2%, respectively. The median progression-free survival was 3.06 months (95% confidence interval [CI], 2.20-4.14 months). The median overall survival was 7.69 months (95% CI, 5.36 months to not estimable). The most common treatment-related adverse events were hand-foot-skin reaction (30.0%), proteinuria (27.5%), oral mucositis (22.5%), fatigue (20.0%), and hypertension (17.5%). Nine patients received apatinib after progression, and the median duration of apatinib therapy beyond progression was 5.13 months (95% CI, 4.27-7.82 months).. Apatinib shows promising efficacy and manageable toxicity in patients with advanced non-squamous non-small-cell lung cancer. Apatinib therapy beyond progression could provide further benefits in specific subpopulations.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pyridines; Survival Analysis; Treatment Outcome; Vascular Endothelial Growth Factor Receptor-2

Topics: Carcinoma, Non-Small-Cell Lung; Cisplatin; Humans; Lung Neoplasms; Paclitaxel

Lung cancer is the leading cause of cancer-associated mortality worldwide. Central nervous system (CNS) metastasis is a prevalent and serious complication. The most common treatment for brain metastasis (BM) is still radiation therapy (RT). An increasing number of drugs have been shown to have intracranial activity or to sensitize tumours to radiotherapy.. Consecutive advanced multiline therapy failure in patients with non-small-cell lung cancer (NSCLC) with BM at the authors' hospital were retrospectively reviewed. Eligible patients were divided into two groups: Apatinib+RT group and RT group. Intracranial progression-free survival (PFS) and overall survival (OS) were analysed using the Kaplan-Meier method.. The median intracranial PFS for the RT group and Apatinib+RT group was 5.83 months and 11.81 months (. RT combined with apatinib could help to control intracranial metastases. The Apatinib+RT group had significantly reduced symptoms caused by BM and improved quality of life for patients, the safety of the two treatments was similar.. Here, we propose that RT combined with apatinib can significantly relieve brain symptoms and tolerate side-effects without affecting OS in patients with BM following failure of multiline therapy for NSCLC. Of course, this paper is a retrospective origin study, and more powerful evidence is needed to demonstrate.

Topics: Antineoplastic Agents; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Quality of Life; Retrospective Studies

Apatinib combined with gefitinib was proven to benefit advanced EGFR-mutant NSCLC patients in first-line treatment. This study aimed to evaluate the drug-drug interaction of gefitinib and apatinib when coadministered in EGFR-mutated NSCLC patients.. In this phase 1b, multi-center, open-label, fixed-sequence study, the drug-drug interaction of gefitinib and apatinib was evaluated when coadministered in EGFR-mutated NSCLC patients. Patients received single-agent apatinib 500 mg QD on days 1-4. Gefitinib 250 mg QD was given on days 5-15 and combined with apatinib 500 mg QD on days 12-15. Serial blood samples were drawn on days 4 and 15. The plasma concentrations and other pharmacokinetics parameters were measured for apatinib with and without gefitinib.. The study enrolled 22 patients and 20 were analyzed for pharmacokinetics. There were no distinct differences in apatinib C. Apatinib pharmacokinetics parameters were not significantly changed when coadministered with gefitinib. All TEAEs were manageable, and there was no need to change the dose level when combining apatinib and gefitinib (ClinicalTrials.gov identifier: NCT04390984, May 18, 2020).

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Feasibility Studies; Gefitinib; Humans; Lung Neoplasms; Mutation; Protein Kinase Inhibitors

The efficacy of apatinib has been confirmed in the treatment of solid tumors, including non-small-cell lung cancer (NSCLC). However, the direct functional mechanisms of tumor lethality mediated by apatinib and the precise mechanisms of drug resistance are largely unknown. In this study, we demonstrated that apatinib could reprogram glutamine metabolism in human NSCLC via a mechanism involved in amino acid metabolic imbalances. Apatinib repressed the expression of GLS1, the initial and rate-limiting enzyme of glutamine catabolism. However, the broken metabolic balance led to the activation of the amino acid response (AAR) pathway, known as the GCN2/eIF2α/ATF4 pathway. Moreover, activation of ATF4 was responsible for the induction of SLC1A5 and ASNS, which promoted the consumption and metabolization of glutamine. Interestingly, the combination of apatinib and ATF4 silencing abolished glutamine metabolism in NSCLC cells. Moreover, knockdown of ATF4 enhanced the antitumor effect of apatinib both in vitro and in vivo. In summary, this study showed that apatinib could reprogram glutamine metabolism through the activation of the AAR pathway in human NSCLC cells and indicated that targeting ATF4 is a potential therapeutic strategy for relieving apatinib resistance.

Topics: Amino Acid Transport System ASC; Amino Acids; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Glutamine; Humans; Lung Neoplasms; Minor Histocompatibility Antigens; Pyridines

Anti-angiogenesis drugs are applicable in treating advanced non-small cell lung cancer (NSCLC); however, the related data regarding apatinib, a Chinese domestic anti-vascular endothelial growth factor receptor-2 (VEGFR-2) production, are limited. Therefore, this study explored the efficacy and safety of apatinib plus platinum doublet chemotherapy in treating patients with advanced NSCLC.. Twenty-four patients with advanced NSCLC were retrospectively enrolled. All patients received platinum doublet chemotherapy combined with apatinib 250 mg daily. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events were analyzed.. Zero (0.0%), seven (29.2%), 11 (45.8%), and six (25.0%) patients had partial response (PR), stable disease (SD), and progressed disease (PD), respectively, resulting in an ORR of 29.2% and a DCR of 75.0%. The median PFS was 12.6 months (95% CI: 3.9-21.3 months) with a 1-year PFS of 56.1%, and the median OS was 18.3 months (95% CI: 13.0-23.5 months) with a 1-year OS of 73.9%. Age ≤60 years (P = 0.034), ECOG performance score 1 (vs. 2; P = 0.005), and first-line treatment (vs. second or higher line treatment; P = 0.043) correlated with longer PFS. The most common treatment-related adverse events included fatigue (83.3%), nausea (79.2%), myelosuppression (70.8), and vomiting (66.7%), while most of them were mild and manageable. Only four (16.6%) patients witnessed grade 3-4 myelosuppression.. Apatinib plus platinum doublet chemotherapy is effective and well-tolerated in treating patients with advanced NSCLC; moreover, reduced ECOG PS and lower lines of treatment relate to its better efficacy.

Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Middle Aged; Platinum; Prognosis; Pyridines; Retrospective Studies; Vascular Endothelial Growth Factor Receptor-2

To evaluation the clinical efficacy and safety of bronchial artery chemoembolization (BACE) combined with apatinib for treatment of advanced central lung squamous cell carcinoma (LSCC).. Forty-seven patients with pathologically diagnosed stage IIIB or IV central LSCC that was not resectable were selected among hospital patients presenting after November 2016. Twenty-one patients were treated with BACE combined with apatinib; the remaining patients served as a control group treated with BACE alone. Objective response rate (ORR) and disease control rate (DCR) were evaluated with postoperative contrast-enhanced CT scans at 3, 6, and 12 months. Progression-free survival (PFS) curves were used to evaluate curative effects. Adverse events were recorded to assess safety.. BACE operations were successfully completed in all 47 patients. Significant differences were found at six and 12 months (P < 0.05). Median PFS was 322 days in the observation group and 209 days in the control group: a statistically significant difference (P = 0.042). One-year survival rates were 76.19% and 46.15% for observation and control patients, respectively; this difference was also significant (P = 0.037). Three patients in the observation group received emergency interventional embolization for hemoptysis, and patients with grade III or greater adverse reaction events (AE) accounted for 19.05% of patients (4/21); these subjects improved or were controlled after active treatment.. BACE combined with apatinib is effective for treatment of advanced central LSCC, with definite short-term efficacy, controllable risk, and high safety. Investigation with a larger sample size is warranted to confirm study results.

Topics: Bronchial Arteries; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Humans; Lung; Lung Neoplasms; Pyridines

This study aimed to analyze the predictive value of the neutrophil-to-lymphocyte ratio (NLR) to better clarify which patients with advanced non-small cell lung cancer (NSCLC) would benefit most from apatinib after multiline treatment for drug resistance. This observational cohort study involved patients with advanced NSCLC who were treated with apatinib between May 2016 to May 2018. The participants in this study had previously been treated with at least two treatment regimens. Multivariate logistic regression and Cox proportional risk models were used to evaluate the overall survival (OS) and progression-free survival (PFS) of the pretreatment NLR. A total of 125 patients were reviewed. The median age was 64 years (range, 33-92); and 32.8% of the patients were female. Only 0.8% of the patients had an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score ≥ 2. In multivariate analysis, pretreatment NLR ≥ 5 had an independent correlation with inferior OS (median 2.07 vs 3.40 months; HR 1.493, 95% CI 1.022-2.182; P = .038) and inferior PFS (median 1.83 vs 2.76 months; HR 1.478, 95% CI 1.015-2.153; P = .042). Elevated pretreatment NLR is associated with shorter OS and PFS in patients with advanced NSCLC treated with apatinib after multiline treatment for drug resistance.

Topics: Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Lymphocytes; Male; Middle Aged; Neutrophils; Survival Rate

Extensive clinical studies have indicated that the epidermal growth factor receptor (EGFR)- tyrosine kinase inhibitors (TKIs) can significantly improve the survival rate of patients with EGFRmutation-positive malignancies. However, acquired resistance to the third-generation EGFR-TKI osimertinib is an intractable obstacle for many clinical oncologists. The resistance mechanism of osimertinib is very complicated, and the individual treatment varies greatly. We present the case of a 76-year-old woman with advanced non-small cell lung cancer (NSCLC) with EGFR L858R mutation, as well as multiple lung metastases and multiple liver metastases. The patient's lung lesions progressed after almost 2 years of treatment with Osimertinib. Due to poor physical condition, she could not tolerate chemotherapy or invasive examination. A next-generation sequencing (NGS) panel of a plasma sample showed missense mutations of KRAS (G12S), MET (D1028Y), AR (S697P), LRP1B (S2662C) with allelic frequencies of 0.6%, 0.5%, 0.2%, 0.2%, respectively), 2 nonsense mutations [ZNF521 (E307*), MET (Q42*), with allelic frequencies of 0.5%, 0.3%, respectively], and a splicing mutation in FAT1 (c.3266-1G>C) with an allelic frequency of 0.5%. After treatment with camrelizumab (200 mg fortnightly) combined with small dose of apatinib (125 mg qd), the patient's lung lesions were successfully overcome with significant reduction and necrosis formation. And the patient's symptoms were significantly relieved and was well tolerated. To our knowledge, this is the first report on the successful treatment of such patients. It indicated a promising treatment option in the clinic to the NSCLC with osimertinib resistance.

Topics: Acrylamides; Aged; Aniline Compounds; Antibodies, Monoclonal, Humanized; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Pyridines

Targeted therapy has become the main treatment for non-small cell lung cancer (NSCLC). Apatinib is a new antiangiogenic antitumor drug developed in China which targets vascular endothelial growth factor receptor-2 (VEGFR-2). We recently treated a 50-year-old female patient who underwent a bronchoscopic biopsy and was subsequently pathologically diagnosed with squamous cell carcinoma of NSCLC. EML4-ALK and MINPP1 & PAPSS2-PTEN fusions were found to be present in tumor tissue and blood. Sequential targeted therapy was commenced with gemcitabine + cisplatin, docetaxel, tegafur, gimeracil, oteracil potassium capsules + carboplatin, and other third-line chemotherapy involving antineoplastic therapy, but unfortunately the patient showed primary drug resistance to this treatment regimen. Crizotinib was administered but was found to be ineffective. After two months of treatment, the disease had progressed and next generation sequencing (NGS) was subsequently performed. Apatinib was administered thereafter and the patient's symptoms improved after one week. Following administration for one month, CT scan revealed that the primary lung tumor lesions were significantly necrotic and they were narrowed. The patient's symptoms of coughing, phlegm production, and wheezing had also reduced. Her lung disease was under stable control 2.5 months later, but abdominal CT unfortunately revealed a suspected new nidus in the liver. A third gene mutation detection test showed that ALK and PTEN genetic mutations were obviously decreased; however, the patient was found to have developed WRN p.V697F (c.G2089T) point mutation, which was a new gene mutation. We suspected that the WRN gene mutation had led to apatinib resistance. We determined the absolute position of this point mutation to be chr8:30969131 with a transcript number of NM_000553.4. We retrieved information on human somatic cells from the ExAC, 1000 Genomes Browser, ESP database and PubMed databases. All the results indicated that the mutation identified in this study has not been previously reported worldwide.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Non-Small-Cell Lung; Drug Resistance, Neoplasm; Female; Humans; Lung Neoplasms; Phosphatidylinositol 3-Kinases; Point Mutation; Proto-Oncogene Proteins c-akt; Pyridines

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; China; Combined Modality Therapy; Disease-Free Survival; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Protein Kinase Inhibitors; Pyridines; Vascular Endothelial Growth Factor Receptor-2

In the tumor vascular system, the vascular structure is disordered, the morphology is abnormal, and the structure of the blood vessel walls is incomplete, leading to leakage of the blood vessel wall, elevated interstitial fluid pressure, and elevated blood flow resistance. These alterations lead to local microenvironmental changes, which mainly manifest as a lack of oxygen and acidosis, further affecting the efficacy of chemotherapy drugs. Antiangiogenic drugs can normalize the abnormalities caused by tumor angiogenesis, thereby transferring oxygen and drugs to tumor cells more efficiently through normalized blood vessels and enhancing the efficacy of chemotherapy drugs. Apatinib is a specific VEGFR-2 inhibitor that blocks the transmission of the VEGF/VEGFR-2 signaling pathway. In this study, we constructed a nude mouse xenograft model of lung cancer and administered apatinib at different doses and times to detect the normalization of reactive blood vessels through VEGF, α-SMA, college-IV, HIF-1α, and MMP. The ultrastructure of tumor blood vessels was observed by electron microscopy, and the dose and timing of apatinib-induced normalization of lung cancer in nude mice were confirmed. Then, we observed the inhibitory effect of apatinib combined with pemetrexed on transplanted tumors of lung cancer cells in nude mice at different time points and observed whether combination pemetrexed chemotherapy showed more significant effects in the time window of vascular normalization induced by apatinib. The inhibition of the growth of transplanted tumors was examined. Then 20 patients with advanced non-small cell lung cancer were enrolled, and apatinib sequential chemotherapy drugs were applied as a third-line chemotherapy regimen to observe its clinical efficacy.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Proliferation; Female; Humans; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Neovascularization, Pathologic; Prognosis; Pyridines; Retreatment; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

The purpose of this study was to analyze the safety and feasibility of low-dose apatinib combined with S-1 as a second-line therapy or beyond in Chinese patients with pulmonary and/or hepatic metastases of nasopharyngeal carcinoma (NPC).. Forty-one Chinese NPC patients with pulmonary and hepatic metastases were treated with low-dose apatinib plus S-1. The S-1 dose was determined according to each patient's body surface area (BSA): 40 mg twice a day for BSA <1.25 m. Treatment efficacy was evaluated in all 41 patients after four courses of chemotherapy. The objective response rate was 34.1%, and the disease control rate was 80.4%. The median progression-free survival was 9.7 months (95% confidence interval, 6.2-13.8 months), and the median overall survival was 22.1 months (95% confidence interval, 15.1-28.9 months). The 2-year survival rate was 41.5%. The most common toxicities included loss of appetite in 39.0% of patients, dyslipidemia in 34.1%, hypertension in 31.7%, myelosuppression in 24.4%, fatigue in 21.9%, and hand-foot syndrome in 17.1%. Seven patients received dose adjustment of apatinib due to side effects.. In patients with pulmonary and/or hepatic metastases of NPC, low-dose apatinib plus S-1 yielded an excellent survival benefit, and the toxicities were mild and tolerable.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Asian People; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Oxonic Acid; Pyridines; Survival Rate; Tegafur; Young Adult

Apatinib is a novel anti-angiogenic agent that targets vascular endothelial growth factor receptor-2, and is effective in patients with advanced lung cancer who are refractory to first-line chemotherapy. However, there are limited reports on concurrent apatinib therapy with iodine-125 radioactive seeds brachytherapy in elderly patients with advanced lung cancer.. We describe the first reported case of a 70-year-old woman with advanced lung cancer (T3N3M1, stage IV) who received concurrent apatinib and iodine-125 radioactive seeds brachytherapy after the failure of platinum-based doublet chemotherapy DIAGNOSIS:: The patient was diagnosed with left lower lung cancer with mediastinal lymph node metastasis by chest computed tomography.. Initially, apatinib alone was used as second-line cancer therapy. Subsequently, the patient received concurrent apatinib and iodine-125 radioactive seeds brachytherapy.. The patient achieved partial response shortly after undergoing treatment with only apatinib. During the treatment, the tumor continued to respond to apatinib therapy, and the lung metastases were diminished eventually. However, a chest computed tomography scan showed a large cavity in the lung tumor. Thereafter, the patient received concurrent apatinib and iodine-125 radioactive seeds brachytherapy. Unfortunately, she died due to pulmonary infection.. Apatinib alone may be a good second-line therapy for advanced lung cancer patients who are refractory to platinum-based doublet chemotherapy. However, its potential benefits, especially as combination therapy, need further investigation by future prospective clinical studies. Elderly patients with advanced lung cancer may benefit from concurrent apatinib with iodine-125 radioactive seeds brachytherapy when chemotherapy is not tolerated or effective. Further studies are needed to investigate the clinical outcomes and toxicities associated with concurrent apatinib and radiation therapy in patients with advanced lung cancer.

Topics: Aged; Antineoplastic Agents; Brachytherapy; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Female; Humans; Iodine Radioisotopes; Lung Neoplasms; Lymphatic Metastasis; Neoplasm Staging; Pyridines

The prognosis of advanced non‑small cell lung cancer (NSCLC) is poor; therefore, identifying novel treatment strategies for patients with NSCLC is important. The present study aimed to investigate the efficacy of apatinib plus docetaxel vs. docetaxel alone, as well as their effects on regulating autophagy markers in patients with advanced NSCLC. Furthermore, it was evaluated whether apatinib sensitized chemoresistant NSCLC cells to docetaxel via regulating autophagy. A total of 39 patients with advanced NSCLC were consecutively enrolled and treated with apatinib plus docetaxel (n=19) or docetaxel alone (n=20) for four treatment cycles. The treatment response, adverse events and expression levels of autophagy markers [(light chain 3 α (LC3A) and Beclin‑1] were evaluated in tumor samples, which were obtained via biopsy, before treatment and after 2‑cycle treatment. In addition, in a mechanistic in vitro experiment, apatinib, docetaxel, the autophagy activator rapamycin and the autophagy inhibitor 3‑methyladenine (3‑MA) were used to treat docetaxel‑resistant A549 (A549/DTX) cells alone or in various combinations. The expression levels of LC3A, Beclin‑1, poly (ADP) ribose polymerase (PARP) and phosphorylated (p)‑AKT were detected via western blotting, while the cell apoptosis rate was detected with an Annexin V/PI assay. The overall remission rate (37 vs. 10%; P=0.047) and disease control rate (84 vs. 45%; P=0.011) were increased in the Apatinib plus docetaxel group compared with the Docetaxel group. Most of the adverse events were mild and tolerable, and there was no difference between the two groups except for total hypertension and hand‑foot syndrome, which were higher in the Apatinib plus docetaxel group). Compared with the levels prior to treatment, Beclin‑1 and LC3A remained unchanged post‑treatment in the Apatinib plus docetaxel group, while they were increased in the Docetaxel group. Docetaxel increased LC3A, Beclin‑1 and p‑AKT expression levels, PARP cleavage and the cell apoptosis rate in A549/DTX cells, and rapamycin further enhanced, while 3‑MA reduced these effects of docetaxel. Moreover, apatinib repressed LC3A, Beclin‑1, p‑AKT expression levels and promoted the cell apoptosis rate in A549/DTX cells and docetaxel‑treated A549/DTX cells. In conclusion, apatinib synergize the effect of docetaxel in treating patients with advanced NSCLC and chemoresistant NSCLC cells via inhibiting autophagy.

Topics: A549 Cells; Aged; Autophagy; Beclin-1; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Cell Survival; Docetaxel; Drug Resistance, Neoplasm; Drug Synergism; Female; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Male; Microtubule-Associated Proteins; Middle Aged; Pyridines

The aim of this study was to investigate the feasibility of using a combination of apatinib in the treatment of non-small cell lung cancer. Apatinib is a tyrosine kinase inhibitor which selectivelyacts on vascular endothelial growth factor receptor 2 (VEGFR-2) and has shown good efficacy in a variety of malignancies, but the drug resistance is fast in single drug therapy.. The inhibitory effect of apatinib and other drugs on lung cancer cells was determined by CCK-8 test in vitro, and the IC50 value was determined. To establish a nude mouse xenograft model, observe the inhibitory effect of apatinib combined with other drugs on lung cancer xenografts in nude mice; immunohistochemical staining of tumor microvessel density and Ki67 expression in transplanted tumor tissues; Western blot analysis of related signaling pathways expression; immunohistochemistry was used to detect tumor microvessel density in other organs and to observe its safety.. In this study, we found apatinib combined with pemetrexed, the first and third generation of epidermal growth factor receptor tyrosine kinase inhibitor, could synergistically inhibit the proliferation of non-small cell lung cancer cell (NSCLC) lines, reduce the microvessel density and Ki67 protein levels of three non-small cell lung cancer xenografts, and enhance anti-tumor activity by synergistically inhibiting the MAPK-ERK and PI3K-AKT-mTOR signaling pathway. Furthermore, there were no pathological abnormalities in the heart, brain, liver and kidney of each group.. The efficacy of apatinib combination is better than that of monotherapy, and there is no significant difference in toxicity of important organs, which suggests the feasibility of a combination of apatinib in the treatment of non-small cell lung cancer.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Survival; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Humans; Immunohistochemistry; Lung Neoplasms; Mice; Molecular Targeted Therapy; Pyridines; Xenograft Model Antitumor Assays

No standard methods are recommended for patients with advanced metastatic non-small-cell lung cancer (NSCLC) experiencing progression after 2 or more lines treatment now. The aim of this retrospective study was to assess the efficacy and safety of apatinib in metastatic NSCLC patients after second-line or more treatments failure in a real-world setting.A total of 52 advanced NSCLC patients who experienced progression after second-line and more treatments and received apatinib from March 2016 to February 2018 were retrospectively reviewed. Patients were treated with oral apatinib 500 mg QD (take the medicine once a day), every 4 weeks for a cycle. Responding and stable patients continued the treatment until progression or intolerable toxicity. The overall survival (OS), progression-free survival (PFS), objective remission rate (ORR) and disease control rate (DCR), and side effects of the drug were collected and reviewed.The ORR and the DCR were 6.9% and 67.4%. The median PFS and median OS of all patients were 3.8 months and 5.8 months, respectively. The Eastern Cooperative Oncology Group score was the independent influencing factor of PFS and OS for the advanced NSCLC patients who were treated with apatinib after second-line and above standard regimens (PFS: hazard ratio [HR] = 4.446, 95% confidence interval [CI]: 1.185-16.678, P = .027 and OS: HR = 8.149, 95% CI: 1.173-56.596, P = .034). The most common adverse events apatinib-related included hypertension (19.2%), hand-foot syndrome (11.5%), and mucous membrane reaction (17.3%). And treatment-related grade 3/4 toxicities were low.Apatinib showed favorable efficacy and safety and could be a treatment option in patients with advanced NSCLC experiencing progression after second-line and more treatment.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Disease Progression; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Pyridines; Retrospective Studies

Camrelizumab is a promising anti-programmed cell death-1 agent for non-small cell lung cancer (NSCLC) and induces reactive capillary hemangiomas (RCHs). Routine clinical management of this unique and prevalent toxicity has been summarized in previous studies. The objective of this study was to provide evidence of apatinib as a salvage therapy for RCHs.. In this single-center, observational study, patients with NSCLC who were over 18 years of age and treated with camrelizumab were enrolled. The incidence of RCHs, onset and duration time, severity, evolution, and clinical practices, especially with apatinib, for their management and impact on quality of life, were recorded during a 6-month follow-up.. A total of 28 patients were included. The incidence of RCHs was 28.6% (8/28). The median onset and duration time were 6 weeks and 8 weeks, respectively. Six (21.4%) patients had mild and moderate RCHs and four (9.3%) patients achieved a rapid regression of RCHs with the application of apatinib. The impact of the RCHs on quality of life was limited and assessed with Dermatology Life Quality Index scores. No treatment-associated termination was observed.. The combination of camrelizumab and apatinib in the treatment of NSCLC reduced the incidence of RCHs. Apatinib appeared to be a salvage therapy of RCHs, which leads to rapid regression of RCHs with no impairment on the quality of life.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Biopsy; Carcinoma, Non-Small-Cell Lung; Female; Hemangioma, Capillary; Humans; Immunohistochemistry; Incidence; Lung Neoplasms; Male; Middle Aged; Pyridines; Salvage Therapy; Treatment Outcome

Apatinib is an oral TKI with antiangiogenic properties, and it is currently approved for the treatment of advanced gastric cancer in China. This agent has also been tested in other human solid tumors, including non-small cell lung cancer (NSCLC). Since the combination of chemotherapy and an antiangiogenic agent has been shown to be a feasible strategy in NSCLC, it is conceivable that a similar approach combining apatinib with chemotherapy may yield clinical activity. With this in mind, we investigated the efficiency of apatinib in combination with pemetrexed or docetaxel in advanced NSCLC. We treated a total of 20 patients with metastatic NSCLC adenocarcinoma with apatinib in combination with either pemetrexed or docetaxel from January 2016 to March 2017. The performance status of these patients was 0 or 1. All of these patients had been previously treated with two or more lines of treatment and had experienced disease progression prior to study enrollment. The overall objective response rate (ORR) was 30%, with 6 patients who had partial response (PR), 10 patients who had stable disease (SD), and 4 patients who had progressive disease (PD). The main adverse events were skin rash, hypertension, palmar-plantar erythrodysesthesia syndrome, diarrhea, and fatigue. Nearly 30% of patients required interruption of treatment as a result of toxicity. Our study demonstrated that apatinib combined with systemic cytotoxic chemotherapy has clinical efficacy in patients with disease-refractory metastatic NSCLC and provides evidence for further studies investigating apatinib-based combination regimens.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Molecular Targeted Therapy; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Protein Kinase Inhibitors; Pyridines; Survival Analysis; Tomography, X-Ray Computed; Treatment Outcome

Platinum-based doublet chemotherapy and radiotherapy are the standard treatment option in advanced squamous cell carcinoma patients. However, few agents could be selected for subsequent post-second-line treatment. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase, apatinib had been proved in advanced gastric cancer. Here, we showed its efficacy and safety in lung squamous cell carcinoma.. In this retrospective study, 13 advanced lung squamous cell carcinoma patients were enrolled. They received doublet chemotherapy or docetaxel as the first-line treatment. After disease progressed, all patients were administrated apatinib monotherapy (250-425 mg/day) for second-line or fourth-line therapy.. After apatinib monotherapy, two patients achieved partial response, four patients achieved stable disease, and seven patients achieved progression disease. The medium PFS was 3.1 months. The median OS had not yet been reached. The objective remission rate was 15.4% (2/13). The total disease control rate was 46.2% (6/13). The main advert effects were vomiting and hypertension.. Apatinib might be an option as rescue treatment in advanced lung squamous cell carcinoma.

Topics: Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Disease Progression; Dose-Response Relationship, Drug; Female; Humans; Hypertension; Lung Neoplasms; Male; Middle Aged; Progression-Free Survival; Protein Kinase Inhibitors; Pyridines; Retrospective Studies; Vascular Endothelial Growth Factor Receptor-2; Vomiting

For advanced non-small-cell lung cancer (NSCLC), targeted therapy and chemoradiotherapy are recommended as the first-line treatment. For patients with a performance status (PS) score over 2 and without gene mutation, however, only supportive treatment is provided and survival time is extremely short. We believe that more can be done to improve the patient's survival time and their quality of life.. A 65-year-old female came to our hospital due to "cough and pain and lack of movement in the left leg". The diagnosis was advanced wild gene-type lung adenocarcinoma and PS score over 2.. She was treated in our clinic with apatinib and erlotinib and has had no progression of the disease for 15.4 months. Except for the presence of hand-foot syndrome and diarrhea, no other serious adverse reactions were seen.. For patients in poor physical condition and unacceptable of chemo-radiotherapy, apatinib combined with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is a safe and effective therapeutic method for advanced wild gene-type NCSCL.

Topics: Aged; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Erlotinib Hydrochloride; Female; Humans; Karnofsky Performance Status; Protein Kinase Inhibitors; Pyridines; Treatment Outcome

Lung cancer is the leading cause of cancer-associated deaths all over the world. Although the prognosis of lung cancer has improved over the past decade due to progression in surgical techniques and systematic treatments, the patients with advanced disease still suffer poor survival. There are no standard treatment strategies for patients who have failed to respond to at least 2 lines of chemotherapy in non-small cell lung cancer (NSCLC). Apatinib, one of the latest small-molecule oral anti-angiogenesis targeted agents developed first in China, has shown remarkable anti-tumor efficacy in a variety of solid tumor types.. A 72-year-old woman underwent radical resection of the left lung cancer in July 2011, but was found a recurrence of cancer after 2 years.. The histopathological examination of the resected specimen identified the lesion as lung adenocarcinoma.. She received gemcitabine and carboplatin regimen as adjuvant chemotherapy for 4 cycles following the surgery in August 2011. After the tumor relapsed, she received multiple lines of chemotherapy including paclitaxel, cisplatin, docetaxel, and gemcitabine from July 2013, but still suffered progressive disease in February 2017. Then apatinib alone was used to defend against the tumor at a dose of 250 mg/d orally till December 2017.. The efficacy was assessed as partial response 1 month later in March 2017. And the use of apatinib was continued till the patient died of tumor progression, achieving a progression-free survival for 10 months. During the treatment with apatinib, the patient experienced hypertension of grade 1, which was well-tolerated and manageable.. Apatinib might be efficient and well-tolerated for patients with advanced NSCLC who have failed to respond to multi-line treatments, even at a low dose.

Topics: Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Female; Humans; Lung Neoplasms; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyridines

Apatinib, an oral tyrosine kinase inhibitor mainly targeting VEGFR-2, exerts both antiangiogenesis and antiproliferation effects. Apatinib shows clinical benefit in advanced non-small cell lung cancer (NSCLC) at an initial dose of 750 mg qd. We further assessed the efficacy and safety of apatinib at a more frequently used dose of 500 mg qd. The preliminary clinical outcome of apatinib in patients with brain metastases was also reported.. We retrospectively reviewed the clinical data of 25 patients who received apatinib between August 2015 and May 2016. Progression-free survival (PFS) was calculated by using the Kaplan-Meier method.. The objective response rate and disease control rate were 8.0% and 68.0%, respectively. The median PFS was 5.17 (95% confidence interval [CI]: 0.76-9.57) months. In the second-line setting (n = 13), the median PFS was 7.37 (95% CI: 0.01-14.72) months, whereas the median PFS for the 12 patients treated with apatinib as third line or beyond therapy was 5.17 (95% CI: 1.78-8.55) months. Of the seven patients with brain metastases, four patients had stable disease. All patients were well tolerant to apatinib without any grade 3 or 4 adverse events. The most common grade 1 or 2 adverse events included hypertension (72.0%), hand-foot-skin reaction (24.0%), fatigue (24.0%) and abnormal liver function (20.0%).. Apatinib is effective and well tolerated in patients with advanced NSCLC, even at a dosage of 500 mg qd, and might offer a new option for the treatment of such patients with brain metastases.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pyridines; Retrospective Studies

Apatinib, a tyrosine kinase inhibitor which selectively inhibits vascular endothelial growth factor receptor-2, has been shown to be beneficial to patients with a variety of cancers, including advanced nonsmall-cell lung cancer (NSCLC). Thus, this study was aimed to retrospectively assess the efficacy and safety of apatinib in patients with advanced/metastatic NSCLC who failed more than two lines of treatment.. Twenty-three NSCLC patients were involved in this study, who received oral apatinib at a daily dose of 250/500/750 mg, with the progression after the failure of second-line therapy. Treatment was continued until disease progression. The tumor assessments were determined according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Safety was evaluated with adverse reactions and toxicities based on the Common Terminology Criteria for Adverse Events (version 4.0). Response and safety for the included patients were evaluated every 8 weeks.. In this study, 23 NSCLC patients were followed from January 2015 to December 2016. Available image efficacy was obtained in 22 patients, including 4 identified as partial responses, 17 stable disease, and 1 progressive disease; no complete responses was observed. The objective response rate was 18.2%, and the disease control rate was 95.5%. Median progression free survival and overall survival for apatinib were 203 days (95% CI, 120-269) and 227 days (95% CI, 146-294), respectively. The most frequent treatment-related adverse events were hypertension, gastrointestinal reactions, and hand-foot skin reaction.. Apatinib exhibited modest activity and acceptable toxicity for advanced NSCLC after the failure of chemotherapy or other targeted therapy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Protein Kinase Inhibitors; Pyridines; Retrospective Studies; Survival Analysis; Treatment Outcome

Patients with advanced nonsquamous nonsmall cell lung cancer (NSCLC) who experienced progression with two or more lines chemotherapy have no treatment options that clearly confer a survival benefit. As a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, apatinib has a certain antitumor effect for various solid tumors. The present study evaluated the efficacy and safety of apatinib in advanced nonsquamous NSCLC as salvage treatment in Chinese real-world practice.. Twenty-eight patients were enrolled in this observational study from October 2015 to May 2017. Progression-free survival (PFS) and overall survival (OS) were graphed by Kaplan-Meier curve and intergroup comparisons were carried out by log-rank test. Objective response rate (ORR), disease control rate (DCR) and adverse effects (AEs) were also evaluated.. Seven patients obtained partial response, and 18 obtained stable disease, representing an ORR of 26% and a DCR of 93%. Median PFS and OS were 3 (95% confidence interval [CI] 2.6-3.4) and 7.4 (95% CI 1.3-13.5) months, respectively. The efficacy analysis showed that Eastern Cooperative Oncology Group (ECOG) performance status 0-1 was correlated with prolonged OS and PFS (P < 0.05), and hypertension during apatinib treatment was correlated with prolonged OS (P < 0.05). Cox regression showed that ECOG performance status (P < 0.01) (RR = 0.231) (95% CI 0.083-0.642) and hypertension during apatinib treatment (P = 0.05) were predictive indicators for apatinib treatment. Grade 3-4 AEs with incidences of 10% or greater were hypertension (21%), hand-foot syndrome (14%) and proteinuria (11%) which could be relieved by dose reduction.. In conclusion, apatinib has a certain therapeutic effect in patients with advanced nonsquamous NSCLC. ECOG performance status and hypertension during apatinib might be predictive indicators for treatment efficacy.

Topics: Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Male; Pyridines; Safety; Salvage Therapy; Survival Rate; Treatment Outcome

To determine if inhibiting neuropilin-1 (NRP-1) affects the radiosensitivity of NSCLC cells through a vascular endothelial growth factor receptor 2 (VEGFR2)-independent pathway, and to assess the underlying mechanisms.. The expression of VEGFR2, NRP-1, related signaling molecules, abelson murine leukemia viral oncogene homolog 1 (ABL-1), and RAD51 were determined by RT-PCR and Western blotting, respectively. Radiosensitivity was assessed using the colony-forming assay, and the cell apoptosis were analyzed by flow cytometry.. We selected two cell lines with high expression levels of VEGFR2, including Calu-1 cells that have high NRP-1 expression, and H358 cells that have low NRP-1 expression. Upon inhibition of p-VEGFR2 by apatinib in Calu-1 cells, the expression of NRP-1 protein and other related proteins in the pathway was still high. Upon NRP-1 siRNA treatment, the expression of both NRP-1 and RAD51 decreased (p < 0.01; p < 0.05). Upon ABL-1 siRNA treatment, the expression of NRP-1 was increased and the expression of RAD51 was unchanged. Calu-1 cells treated with NRP-1 siRNA exhibited significantly higher apoptosis and radiation sensitivity in radiation therapy compared to Calu-1 cells treated with apatinib alone (p < 0.01; p < 0.01). The apoptosis and radiation sensitivity in H358 cells with NRP-1 overexpression was similar to the control group regardless of VEGFR2 inhibition.. We demonstrated that when VEGFR2 was inhibited, NRP-1 appeared to regulate RAD51 expression through the VEGFR2-independent ABL-1 pathway, consequently regulating radiation sensitivity. In addition, the combined inhibition of VEGFR2 and NRP-1 appears to sensitize cancer cells to radiation.

Topics: Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Humans; Lung Neoplasms; Neuropilin-1; Pyridines; Rad51 Recombinase; Radiation Tolerance; Vascular Endothelial Growth Factor Receptor-2

Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), has proven to be effective and safe for treating patients with advanced gastric cancer after second-line chemotherapy failure. As VEGFR-2 targeted therapy has made encouraging progress for the treatment of a broad range of malignancies, we explored the efficacy and safety of apatinib for the treatment of advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy.. We retrospectively analyzed the data of 34 patients (11 with squamous carcinoma and 23 with adenocarcinoma) who were treated with apatinib alone in a daily oral dose of 250 mg in the second-line or third-line setting from January 2016 to July 2017. The primary endpoint was progression-free survival (PFS).. EGFR mutation or amplification was detected in 15 patients. The median PFS of the whole group was four months (95% confidence interval 0.3-7.7). A partial response was observed in 2 patients (5.88%) and stable disease in 19 (55.88%). The disease control rate was 61.76%. Common side effects of apatinib were hypertension (n = 12), hand-foot syndrome (n = 8), and proteinuria (n = 5), which accounted for 35.30%, 23.53%, and 14.71%, respectively, and no grade 3/4 adverse reactions occurred. Apatinib toxicity was controllable and tolerable.. Apatinib appears to be effective and safe for advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pyridines; Retrospective Studies

Apatinib is a tyrosine kinase inhibitor (TKI) that selectively inhibits the vascular endothelial growth factor receptor-2. A weighted pooled analysis was performed to evaluate the clinical outcome, efficacy, and toxicity of apatinib in patients with advanced nonsmall cell lung cancer (NSCLC) that failed prior treatment with chemotherapy or epidermal growth factor receptor-TKIs (EGFR-TKIs).. The literature published in PubMed, Embase, and Cochrane Library databases was searched (from inception to November 30, 2017) for eligible trials using the following search terms: apatinib AND (lung cancer OR NSCLC). Meeting abstracts were also reviewed to identify appropriate studies. Inclusion criteria were as follows: prospective or retrospective studies that evaluated efficacy and/or safety of apatinib in patients with advanced NSCLC that failed prior chemotherapy or EGFR-TKIs; primary outcome included one of these endpoints, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), or adverse events (AEs); English language; and number of cases in the study ≥10 cases.. A total of 457 patients with advanced NSCLC were treated with apatinib in 14 studies (10 retrospective and 4 prospective studies) and were included in this pooled analysis. The pooled median PFS was 4.77 months [95% confidence interval (CI), 4.11-5.00] in all groups, 4.80 months (95% CI, 4.65-4.95) in the 750 mg apatinib (high-dose) group, and 3.88 months (95% CI, 3.11-4.65) in the 250 to 500 mg apatinib (low-dose) group. Median PFS stratified by single apatinib therapy or apatinib combined with continuous EGFR-TKIs was 4.76 months (95% CI, 3.66-5.06) and 5.20 months (95% CI, 3.66-6.74), respectively. The pooled median OS, ORR, and DCR values were 6.85 months, 18%, and 72%, respectively; pooled median ORR and DCR were 15% and 72% in the 750 mg apatinib group versus 20% and 72% in the 250 to 500 mg apatinib group. ORR and DCR stratified by therapeutic regimens were 14% and 70% for single-agent apatinib, 29% and 88% for apatinib combined with continuous EGFR-TKIs, and 26% and 63% for apatinib combined with chemotherapy, respectively. The pooled AE rates of grade 3/4 were hypertension (7%), proteinuria (3%), hand-foot-skin reaction (6%), fatigue (4%), decreased appetite (1.1%), oral mucositis (3%), and thrombocytopenia (3%).. Apatinib has promising antitumor activity and manageable toxicity profile in patients with advanced NSCLC that failed prior chemotherapy or EGFR-TKIs. This result needs to be confirmed through the ongoing Phase III clinical trial.

Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Dose-Response Relationship, Drug; Female; Humans; Lung Neoplasms; Male; Protein Kinase Inhibitors; Pyridines; Vascular Endothelial Growth Factor Receptor-2

This study was designed to assess the clinical efficacy and toxicity of apatinib (YN968D1) as third or subsequent-line treatment for stage III/IV non-small cell lung cancer (NSCLC).. A total of 100 patients with advanced NSCLC who were treated with apatinib at a daily dose of 250/425/500 mg at Shandong Cancer Hospital from January 2016 to June 2018 were enrolled in our study. The objective response, disease control, and median progression-free survival rates were reviewed and evaluated. Univariate and multivariate analyses were performed to determine the prognostic factors. The main adverse events were evaluated per the Common Terminology Criteria for Adverse Events version 4.0.. All patients were assessable for response. No complete responses were observed, 11 patients achieved a partial response, and 56 showed stable disease. The objective response rate was 11.0%, the disease control rate was 67.0%, and the median progression-free survival was 2.93 months (95% confidence interval 2.07-3.87). In Cox regression analysis, the Eastern Cooperative Oncology Group performance status score (hazard ratio 1.799; P < 0.05) and smoking history (hazard ratio 1.958; P < 0.05) were predictive indicators for apatinib treatment efficacy. Treatment-related adverse events were tolerated, predictable, reversible, and controllable.. Apatinib was found to be both effective and safe in advanced NSCLC patients without a genetic driver mutation who experienced progression after two or more lines of chemotherapy treatment.

Topics: Adult; Aged; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Neoplasm Staging; Proportional Hazards Models; Protein Kinase Inhibitors; Pyridines; Retreatment; Retrospective Studies; Treatment Outcome

The poor prognosis in non-small-cell lung cancer has driven the development of novel targeted therapies. Vascular endothelial growth factor is the most potent force in mediating tumor angiogenesis, and many angiogenesis inhibitors have been developed for oncology treatment. We performed a study to characterize the efficacy, safety and tumor suppression of three lung cancer related anti-angiogenic drugs (bevacizumab, endostar and apatinib) using transgenic zebrafish embryo and human lung cancer xenotransplantation model. All three drugs demonstrated remarkable angiogenesis and tumor inhibition effect in the zebrafish model, within the nonlethal dose range. Endostar and bevacizumab showed competitive anti-tumor efficacy. The anti-tumor performance of apatinib was hamstrung by its elevated toxicity at 35 °C. The addition of pemetrexed to anti-angiogenesis therapy had no obvious additional benefit in tumors.

Topics: A549 Cells; Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Disease Models, Animal; Embryo, Nonmammalian; Endostatins; Humans; Larva; Lung Neoplasms; Pemetrexed; Pyridines; Recombinant Proteins; Transplantation, Heterologous; Xenograft Model Antitumor Assays; Zebrafish

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)-rechallenged therapy for EGFR-mutant non-small cell lung cancer (NSCLC) patients who acquired resistance showed moderate efficacy. Considering the high interrelation between EGFR and vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) pathways, we firstly evaluated EGFR-TKI combined with apatinib (a highly selective VEGFR2 inhibitor) in EGFR-TKI-resistant model and patients.. Effects of apatinib, gefitinib and gefitinib plus apatinib were assessed on four NSCLC cell lines (A549 with wild-type EGFR, H1975 harbouring L858R and T790M, H1650 and HCC827 harbouring E746_A750 deletion) and xenograft model of acquired resistance that was established by injecting H1975 cells. Furthermore, we retrospectively evaluated EGFR-TKI rechallenge with apatinib in 16 patients.. Gefitinib plus apatinib strengthened the effect of gefitinib and apatinib alone on the four NSCLC cell lines, and H1975 was the most susceptible one. Co-administration delayed the tumour growth than mono-therapy in the xenograft model and had better effect on inhibiting the activation of EGFR and VEGFR2 and expression of CD31 (an angiogenesis marker) and vascular endothelial growth factor A (an important pro-angiogenesis factor in the tumour microenvironment). Changes in protein expression of protein kinase B/mammalian target of rapamycin and extracellular signal-regulated kinase pathways demonstrated the potent inhibitory effect on the pro-survival signalling pathways by combined therapy. EGFR-TKI rechallenge with apatinib achieved a median progression-free survival of 4.60 months (95% confidence interval, 2.23-12.52 months) in the patients.. Apatinib significantly potentiated the antitumour effect of gefitinib in NSCLC with T790M-related EGFR-TKI resistance both in vivo and vitro. EGFR-TKI rechallenge with apatinib might represent a new option for NSCLC with T790M or unknown resistance mechanism.

Topics: A549 Cells; Animals; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Cell Proliferation; Disease-Free Survival; Drug Resistance, Neoplasm; ErbB Receptors; Female; Gefitinib; Humans; Lung Neoplasms; Mice, Inbred BALB C; Mice, Nude; Mutation; Protein Kinase Inhibitors; Pyridines; Quinazolines; Retrospective Studies; Signal Transduction; Time Factors; Treatment Outcome; Tumor Burden; Vascular Endothelial Growth Factor Receptor-2; Xenograft Model Antitumor Assays

The efficacy of second or third-line chemotherapy in advanced non-small cell lung cancer (NSCLC) patients is low. The use of targeted drugs brings survival benefit for some patients. Apatinib, as a novel small molecule antiangiogenic drug, has demonstrated satisfactory anticancer activity across a broad range of malignancies. The aim of this study is to evaluate the efficacy and safety of apatinib in patients with advanced NSCLC after first-line treatment failure.. A retrospective study of 128 patients was conducted to evaluate the safety, short-term efficacy and survival status with different regimens. Kaplan-Meier method and Cox regression model were used for analysis.. Compared with chemotherapy alone, the median progression free survival (PFS) in apatinib monotherapy, chemotherapy alone and apatinib combined with chemotherapy were 3.0 (P=0.381), 3.7 and 6.0 months (P<0.001), respectively. The median overall survival (OS) were 6.0 (P=0.494), 6.5 and 9.0 months (P=0.001), respectively. The incidence of adverse events in grades 3-4 were 18.5%, 15.8% and 16.0%, respectively (P=0.947). Different treatment regimens (P=0.018) and performance status (PS)(P<0.001) were the independent factors of PFS. The smoking history (P=0.014), treatment regimens (P=0.002) and PS (P<0.001) were independent influencing factors of OS.. Apatinib has a good security. After first-line treatment failure of lung cancer, chemotherapy combined with apatinib in second or third-line is beneficial in PFS and OS when compared with chemotherapy alone. But when making comparison between apatinib monotherapy and chemotherapy alone, there is no significant difference in PFS and OS. Patients who never smoke or has a better PS or use combination therapy have longer survival time.
.. 背景与目的 晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）的二线、三线化疗有效率较低，靶向药物的应用为部分患者带来生存获益。阿帕替尼是一种新型小分子抗血管生成药物，在多种恶性肿瘤治疗中展现出令人满意的抗癌活性。本研究旨在评价阿帕替尼用于一线治疗进展后晚期非鳞NSCLC的安全性和疗效。方法 回顾性分析128例晚期非鳞NSCLC不同治疗组患者的疗效和生存情况，用Kaplan-Meier法和Cox模型进行分析。结果 以单纯化疗组为对照，阿帕替尼单药组、单纯化疗组和阿帕替尼联合化疗组的中位无进展生存期（progression free survival, PFS）分别为3.0个月（P=0.381）、3.7个月和6.0个月（P<0.001），中位总生存期（overall survival, OS）分别为6.0个月（P=0.494）、6.5个月和9.0个月（P=0.001）。3级-4级不良反应发生率分别为18.5%、15.8%和16.0%（P=0.947）。治疗方案（P=0.018）及体能状态（performance status, PS）（P<0.001）是PFS的独立影响因素，吸烟史（P=0.014）、治疗方案（P=0.002）和PS（P<0.001）是OS的独立影响因素。结论 阿帕替尼安全性高，肺癌一线治疗失败后，二线或三线化疗联合阿帕替尼，与单纯化疗相比，患者有PFS和OS获益，阿帕替尼单药与单纯化疗组间PFS和OS无明显差异；无吸烟史、PS 0分-1分和联合治疗的患者预后更好。.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pyridines; Retrospective Studies

To observe the reversal effect of apatinib on the resistance to cisplatin (DDP) of A549/cisplatin (A549/DDP) cells and its relevant mechanism.. A549/DDP cells were treated with the control method, apatinib alone, DDP alone and DDP combined with apatinib. The cell proliferation was detected by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the cell clone formation assay. The cell apoptosis was detected by Hoechst 33258 staining and annexin V and propidium iodide (PI) double labeling. The changes in apoptotic proteins, multidrug resistance protein 1 (MDR1) and extracellular signal-regulated kinase (ERK) signaling pathway proteins in each group after treatment were detected by Western blotting.. MTT assay results showed that compared with A549 cells, A549/DDP cells had obvious resistance to DDP. MTT assay and cell clone formation assay revealed that the tumor inhibition rate of the sub-lethal dose of apatinib (10 μM) combined with DDP was higher than that of DDP alone. The apoptosis detection results indicated that the proportion of apoptotic cells in the apatinib (10 μM) combined with DDP group was significantly increased. Western blotting results revealed that compared with that in parental A549 cells, the expression level of MDR1 in A549/DDP cells was significantly increased, and the ERK signaling pathway was activated. In the apatinib combined with DDP group, the levels of cleaved caspase-3, cleaved caspase-9 and B-cell lymphoma-2 (Bcl-2)-associated X (BAX) proteins were significantly upregulated, while the level of Bcl-2 proteins was downregulated. Apatinib could inhibit the expression of MDR1 and the activity of the ERK signaling pathway in a dose-dependent manner.. Apatinib can restore the sensitivity of A549/DDP cells to DDP by down-regulating the expression level of MDR1 and inhibiting the activity of the ERK signaling pathway.

Topics: A549 Cells; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B; Carcinoma, Non-Small-Cell Lung; Caspase 9; Cell Line, Tumor; Cisplatin; Drug Resistance, Neoplasm; Humans; Lung Neoplasms; MAP Kinase Signaling System; Pyridines

The outcomes of locally advanced non-small cell lung cancer (NSCLC) remain poor, in particular, the frail elderly patients cannot tolerate chemotherapy. The new efficient, safe, and more specific treatments are needed. Radiation combined with targeted therapy is the focus of research in recent years. Apatinib is highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, studies have revealed that apatinib inhibit the growth of solid tumors including NSCLC. However, there is no report to evaluate its efficacy and safety in combined with radiotherapy for the advanced NSCLC. Our original research about to explore the use of apatinib combined with radiotherapy in treatment of NSCLC and its side effects are as follows.. Patient 1, man, 78-year old, admitted to hospital, due to "thoracalgia and dyspnea for 1 month." Chest and abdomen computed tomography (CT) scan showed that there was a huge mass at the left upper lobe and multiple lymph nodes metastasis in mediastinum and left hilus pulmonis, the diagnosis was left lung squamous cell carcinoma, however, the mass was huge and age of patient was elder, post chemotherapy the mass were bigger and more severe. Patient 2, man, 61-year old, the diagnosis was squamous carcinoma on left upper lobe with right mediastinum lymph notes metastases recrudescence post chemoradiotherapy.. Case 1 was diagnosed left lung huge squamous cell carcinoma and case 2 was left lung squamous carcinoma, the primary lesion and right mediastinum lymph notes metastases recrudescence after radiochemotherapy.. Both patients who received local radiation therapy and concurrent apatinib. Apatinib 250 mg once daily in combination with thoracic radiotherapy (2 Gy/d, 5 fractions/wk) followed by Apatinib Maintenance Therapy.. Favorable oncologic outcomes were achieved in the 2 cases after the treatment. The common side effects of apatinib were hypertension and hand-foot syndrome; however, the toxicity of was controllable and tolerable, no dyspnea, no hemoptysis, no thoracalgia.. Apatinib combined with thoracic radiotherapy, may be an option for recurring or advanced NSCLC. But that still warrants further investigation in the prospective study.

Topics: Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Humans; Lung Neoplasms; Male; Middle Aged; Pyridines