apatinib and Adenocarcinoma

Patients with radioactive iodine refractory progressive (RAIR) differentiated thyroid cancer (DTC) often developed resistance after first-line therapy. Apatinib plus camrelizumab is a therapy with promising efficacy in patients with other malignant cancers. Herein, we presented a case of progressive RAIR DTC treated with apatinib plus camrelizumab.. We reported a 43-year-old man diagnosed as DTC with metastases in the lungs, the 7th cervical vertebra, and malignant lymph nodes mainly in the mediastinum. While initially showing disease stabilization after giving the first-line multitargeted kinase inhibitor (MKI) therapy, the patient developed progressive disease and was enrolled into a combined therapy with both apatinib and camrelizumab on November 10, 2020. Upon the first 6 months, the combination therapy showed disease control in terms of both stable structural lesions and biochemical thyroglobulin (Tg) level. Six months later, a decrease over the targeted lesions was observed and a partial response (PR) according to RECIST 1.1 criteria was finally achieved upon 12 months' assessment, followed by the decline in serum Tg level. The main adverse event was occasional diarrhea without treatment interruption.. We reported a case with RAIR DTC that benefited from combination immunotherapy, apatinib plus camrelizumab, after resistance from donafenib. We observed a gradually getting better efficacy and a mild and long duration of this combination therapy and hoped to provide a therapeutic choice for these patients.

Topics: Adenocarcinoma; Adult; Antibodies, Monoclonal, Humanized; Humans; Immunotherapy; Iodine Radioisotopes; Male; Pyridines; Thyroid Neoplasms

Apatinib has been proven to significantly prolong the survival of the patients with advanced chemotherapy-refractory gastric cancer. To date, studies on apatinib plus S-1 as first-line palliative therapy for metastatic gastroesophageal junction (GEJ) cancer are rare.. A 61-year-old female patient was admitted with dysphagia, significant loss of body weight, and poor performance status.. Endoscopic biopsy revealed the diagnosis of poorly-differentiated GEJ adenocarcinoma, and the patient was clinically staged as T3NxM1G3 (IVB).. She had received 4 cycles of palliative therapy using oral apatinib (425 mg daily) plus S-1 (40 mg twice daily for 4 weeks, with a 2-week drug-free interval), followed by maintenance low-dose apatinib (250 mg daily) plus S-1 at the same dosage thereafter.. Her progression-free survival was nearly 5 months, and the overall survival was >11 months up to now. The adverse events were tolerable.. Apatinib plus S-1 might be an alternative option for late-stage GEJ cancer. However, high-quality trials are warranted before the recommendation of this therapeutic regimen.

Topics: Adenocarcinoma; Antineoplastic Agents; Drug Combinations; Esophageal Neoplasms; Esophagogastric Junction; Female; Humans; Middle Aged; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

About one-third of the lung tumors are staged as locally advanced at the time of initial diagnosis; however, the optimal induction treatment before curative resection has not been elucidated. To date, the evidence regarding the preoperative apatinib plus S-1 for locally advanced pulmonary adenocarcinoma is scarce.. A 29-year-old female was admitted because of persistent cough, sputum, and chest distress for 2 months.. Primary pulmonary adenocarcinoma (cT3N2M0, IIIB) with unknown driver gene mutation status.. The patient had received 4 months of neoadjuvant therapy using oral apatinib (425 mg daily) plus S-1 (60 mg, twice daily for 4 weeks with a 2-week drug-free interval), followed by anatomical lobectomy with curative intent. Adjuvant apatinib (425 mg daily for a month, and 250 mg daily for another month) plus S-1 at the same dosage were administered for 2 months. Thereafter, maintenance of low-dose S-1 monotherapy (40 mg, twice daily for 4 weeks with a 2-week drug-free interval) was continued for 6 months.. The adverse events were tolerable and well-controlled. A postoperative recurrence-free survival for 2 years and a half up to now was indicated.. Preoperative apatinib plus S-1 showed efficacy in locally advanced pulmonary adenocarcinoma. However, high-quality trials are warranted before the recommendation of this therapeutic regimen.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Lung Neoplasms; Neoadjuvant Therapy; Oxonic Acid; Pneumonectomy; Pyridines; Tegafur

Apatinib is a novel anti-angiogenic agent targeting vascular endothelial growth factor receptor-2, which is effective in patients with chemotherapy-refractory gastric cancer. There are no reports of concurrent apatinib with local radiation therapy in elderly patients with advanced gastric cancer. PATIENT CONCERNS AND DIAGNOSES:: we present the first published report of a 70-year-old male patient with advanced gastric cancer who received concurrent apatinib and local radiation therapy after failure of oxaliplatin and S-1 chemotherapy.. The patient received concurrent apatinib and local radiation therapy and was followed up 7 months after therapy without disease progress, 14 months later indicated extensive metastasis and this patient died of pulmonary infection.. Elderly patients with advanced gastric cancer may benefit from concurrent apatinib with local radiation therapy when chemotherapy is not tolerated or successful. Further studies are needed to investigate the clinical outcomes and toxicities associated with concurrent apatinib and radiation therapy in gastric cancer.

Topics: Adenocarcinoma; Aged; Chemoradiotherapy; Humans; Male; Pyridines; Radiotherapy, Intensity-Modulated; Stomach Neoplasms

The prognosis of patients with previously treated advanced gastric or gastroesophageal junction (GEJ) cancer remains poor. Given the robust development of immunotherapy and targeted therapy during the last decades, we aimed to investigate if the combination of traditional second-line chemotherapy with sintilimab and apatinib could bring survival benefits for these patients.. In this single-center, single-arm, phase II trial, patients with previously treated advanced gastric or GEJ adenocarcinoma received specific dose level of intravenous paclitaxel or irinotecan (investigator's choice), 200 mg intravenous sintilimab on day 1, and 250 mg oral apatinib once daily continuously in each cycle until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoints were objective response rate and progression-free survival. The secondary endpoints were mainly overall survival and safety.. From May 2019 to May 2021, 30 patients were enrolled. At the data cutoff date (March 19, 2022), the median follow-up duration was 12.3 months and 53.6% (95% CI, 33.9-72.5%) patients achieved objective response. The median progression-free survival and overall survival were 8.5 months (95% CI, 5.4-11.5) and 12.5 months (95% CI, 3.7-21.3), respectively. Grade 3-4 adverse events included hematological toxicities, elevated alanine aminotransferase, elevated aspartate aminotransferase, elevated alkaline phosphatase, elevated gamma-glutamyl transpeptidase, hyperbilirubinemia and proteinuria. The most frequent grade 3-4 adverse event was neutropenia (13.3%). No serious treatment-related adverse events or treatment-related deaths occurred.. Sintilimab plus apatinib and chemotherapy demonstrates promising anti-tumor activity with manageable safety profile in patients with previously treated advanced gastric or GEJ cancer.. ClinicalTrials.gov: NCT05025033, 27/08/2021.

Topics: Adenocarcinoma; Esophagogastric Junction; Humans; Prospective Studies; Stomach Neoplasms

Apatinib, a highly selective VEGFR2 inhibitor, significantly improved efficacy versus placebo as a third- and later-line treatment for advanced gastric cancer in phase 2 and 3 trials. This prospective, single-arm, multicenter phase IV AHEAD study was conducted to verify the safety and efficacy of apatinib in patients with advanced or metastatic gastric or gastroesophageal adenocarcinoma after at least two lines of systematic therapy in clinical practice settings.. Patients with advanced gastric cancer who had previously failed at least two lines of chemotherapy received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Adverse events were summarized by the incidence rate. Median OS and PFS were estimated using the Kaplan-Meier method. ORR, DCR, OS at 3 and 6 months, and PFS at 3 and 6 months were calculated, and their 95% CIs were estimated according to the Clopper-Pearson method.. Between May 2015 and November 2019, a total of 2004 patients were enrolled, and 1999 patients who received at least one dose of apatinib were assessed for safety. In the safety population, 87.9% of patients experienced treatment-related adverse events (TRAEs), with the most common hypertension (45.2%), proteinuria (26.5%), and white blood cell count decreased (25.3%). Additionally, 51% of patients experienced grade ≥ 3 TRAEs. Fatal TRAEs occurred in 57 (2.9%) patients. No new safety concerns were reported. Among the 2004 patients included in the intention-to-treat population, the ORR was 4.4% (95% CI, 3.6-5.4%), and DCR was 35.8% (95% CI, 33.7-38.0%). The median PFS was 2.7 months (95% CI 2.2-2.8), and the median OS was 5.8 months (95% CI 5.4-6.1).. The findings in the AHEAD study confirmed the acceptable and manageable safety profile and clinical benefit of apatinib in patients with advanced gastric cancer as a third- or later-line of treatment.. This study was registered with ClinicalTrials.gov NCT02426034. Registration date was April 24, 2015.

Topics: Adenocarcinoma; Antineoplastic Agents; Esophagogastric Junction; Humans; Prospective Studies; Stomach Neoplasms

The aim of this study was to analyze the clinical efficacy of Apatinib plus Ba Zhen granules in advanced unresectable differentiated thyroid cancer and its influence on immune factors. Sixty patients with advanced unresectable differentiated thyroid cancer in our hospital between January 2018 and December 2019 were selected and randomized to the control group and the observation group (30 cases in each group). After treatment, the observation group yielded higher serum levels of Cyfra21.1 and Gal-3, but lower SIL-2R levels than the control group. After treatment, the two groups obtained a marked increase in CD3+ and CD4+ levels and a decrease in CD8+ level, in which the observation group has higher levels of CD3+ and CD4+ and lower levels of CD8+ than the control group. After treatment, the serum FT3 and FT4 levels sharply increased and serum TSH levels declined significantly, with higher levels of FT3 and FT4 and lower levels of TSH observed in the observation group. The incidence of adverse reactions didn't significantly differ between groups. In advanced unresectable differentiated thyroid cancer, apatinib remarkably inhibits disease development. The combination of Apatinib and Ba Zhen granules adjusts immune factors and improves thyroid function, with a low incidence of adverse reactions and promising efficacy.

Topics: Adenocarcinoma; Humans; Immunologic Factors; Thyroid Neoplasms; Thyrotropin; Treatment Outcome

The current second-line treatment of advanced gastric or gastroesophageal junction adenocarcinoma remains unsatisfactory. Anti-PD-1 monoclonal antibody combined with anti-angiogenic therapy shows anti-tumor activity and synergistic effect. We aimed to assess the efficacy and safety of the combination therapy of camrelizumab, apatinib, and S-1 in patients with gastric or gastroesophageal junction adenocarcinoma.. In this open-label, single-arm, phase 2 trial, in each 21-day cycle, eligible patients received 200 mg intravenous camrelizumab in the first day, 500 mg oral apatinib once daily continuously, and specific dose oral S-1 in the first 14 days until the trial was discontinued disease progression, development of intolerable toxicity, or withdrawal of consent. The primary endpoint was objective response rate. The secondary endpoints were disease control rate, progression-free survival and overall survival, and safety. This study was registered at ClinicalTrials.gov, NCT04345783.. Between May 2019 and August 2020, we enrolled a total of 24 patients in this trial. At the data cutoff (December 1, 2020), the median follow-up duration was 8.13 months. Seven of 24 (29.2%, 95%CI 14.9-49.2%) patients reached objective response. The median-progression-free survival was 6.5 months (95%CI 6.01-6.99) and the median overall survival was not reached. Grade 3 or 4 adverse events occurred in 6 (25.0%) patients, including elevated transaminase, thrombocytopenia, fatigue, proteinuria, and intestinal obstruction. No serious treatment-related adverse events or treatment-related deaths occurred.. In this trial, the combination of camrelizumab, apatinib, and S-1 showed promising anti-tumor activity and manageable toxicity as a second-line therapy in patients with advanced gastric or gastroesophageal junction adenocarcinoma, regardless of PD-L1 expression.. NCT04345783.

Topics: Adenocarcinoma; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Esophageal Neoplasms; Esophagogastric Junction; Humans; Prospective Studies; Pyridines; Transaminases

Capecitabine plus oxaliplatin (CAPOX) is one of the standard first-line treatments for unresectable, advanced, or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Camrelizumab shows promising antitumor activity in advanced or metastatic G/GEJ adenocarcinoma in a phase I study. We reported the outcomes of cohort 1 in a multicenter, open-label, phase II trial, which assessed camrelizumab in combination with CAPOX followed by camrelizumab plus apatinib as a first-line combination regimen for advanced or metastatic G/GEJ adenocarcinoma.. Systemic treatment-naïve patients with EGFR2-negative advanced or metastatic G/GEJ adenocarcinoma received initial camrelizumab plus CAPOX for 4-6 cycles, and patients without progressive disease were administrated subsequent camrelizumab plus apatinib. Primary endpoint was objective response rate (ORR).. All 48 enrolled patients comprised the efficacy and safety analysis population. The ORR was 58.3% [95% confidence interval (CI), 43.2-72.4] with this combination regimen. Median duration of response was 5.7 months (95% CI, 4.4-8.3). Median overall survival was 14.9 months (95% CI, 13.0-18.6), and median progression-free survival was 6.8 months (95% CI, 5.6-9.5), respectively. The most common grade ≥3 treatment-related adverse events (>10%) were decreased platelet count (20.8%), decreased neutrophil count (18.8%), and hypertension (14.6%). Treatment-related death occurred in 1 patient (2.1%) due to abnormal hepatic function and interstitial lung disease.. Camrelizumab combined with CAPOX followed by camrelizumab plus apatinib demonstrated encouraging antitumor activity and manageable toxicity as first-line therapy for patients with advanced or metastatic G/GEJ adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Esophageal Neoplasms; Esophagogastric Junction; Female; Humans; Male; Middle Aged; Neoplasm Staging; Pyridines; Stomach Neoplasms; Treatment Outcome; Young Adult

The evidence of combining neoadjuvant chemotherapy with targeted therapy for patients with locally advanced gastric cancer is inadequate. We conducted a single-arm phase II trial to evaluate the efficacy and safety of S-1, oxaliplatin and apatinib (SOXA) in patients with locally advanced gastric adenocarcinoma.. Of 29 patients included, median age was 60 (range, 43-73) years; 20 (69.0%) were male. The pRR was 89.7% (95% confidence interval [CI], 72.7%-97.8%; 26 of 29 patients; P < 0.001) with 28 patients treated with surgery. All 29 patients were available for preoperative response evaluation, achieving an objective response rate of 79.3% (95% CI, 60.3%-92.0%) and a disease control rate of 96.6% (95% CI, 82.2%-99.9%). The margin-free resection rate was 96.6% (95% CI, 82.2%-99.9%). The pathologic complete response rate was 13.8% (95%CI, 1.2%-26.3%). Downstaging of overall TNM stage was observed in 16 (55.2%) patients. During neoadjuvant therapy, 10 (34.5%) patients had grade ≥III adverse events. No treatment-related death occurred. Surgery-related complications were observed in 12 of 28 (42.9%) patients.. SOXA followed by surgery in patients with locally advanced gastric adenocarcinoma showed favourable activity and manageable safety. A randomised controlled trial in locally advanced gastric or oesophagogastric junction adenocarcinoma is ongoing (ClinicalTrials.gov: NCT04208347).

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Pyridines; Stomach Neoplasms

To investigate the safety and efficacy of acitinib mesylate combined with chemotherapy in the treatment of patients with gastroesophageal junction adenocarcinoma.. A total of 119 patients with gastroesophageal junction adenocarcinoma were enrolled and randomized into an experimental group (n = 60) and a control group (n = 59). Both groups were treated with a combination of taxane, irinotecan and fluorouracil, while the experimental group also received acitinib mesylate. The clinical efficacy, survival time and adverse reactions of patients in two groups were recorded and analyzed.. The total remission rate in the experimental group and the control group was 15.79% and 3.23%, respectively; the disease control rate was 73.68% and 54.84%, respectively; and progression-free survival was 3.72 months (1-13.5 months) and 3.04 months (1-6 months), respectively. Overall survival was 13.66 months (5-24 months) and 10.08 months (6.5-19.5 months), in the experimental group and the control group, respectively. In addition, the incidence of adverse events in the experimental group was significantly lower than that in the control group.. Apatinib mesylate combined with chemotherapy for the treatment of patients with gastroesophageal junction adenocarcinoma was safe and effective, with improved survival benefit compared with control.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma, Squamous Cell; Case-Control Studies; Cisplatin; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Male; Middle Aged; Prognosis; Pyridines; Stomach Neoplasms; Survival Rate; Taxoids

Apatinib has shown overwhelming efficacy in progressive radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) starting at a 750-mg dosing protocol; however, a relatively high incidence of treatment-associated adverse events (TAAEs) was observed, which reduced quality of life and interrupted the treatment.. To evaluate the efficacy and safety of apatinib with two different dosing schedules [750 or 500 mg once a day (q.d.)] in RAIR-DTC.. Twenty patients were sequentially recruited to receive apatinib beginning at 750 (n = 10) or 500 (n = 10) mg q.d. Efficacy and safety were compared in each 28-day cycle at the beginning two cycles and every two cycles thereafter.. After six treatment cycles, the best disease control rates were 100% for the 750- and 500-mg schedules, respectively, and the best objective response rates were 90.0% and 70.0% (P = 0.58), respectively. The two dosing schedules did not differ regarding greatest reduction in target lesion size (-42.7% vs -40.5% for the 750- vs 500-mg schedule, P = 0.48) and thyroglobulin level (-82.5% vs -94.3% for the 750- vs 500-mg schedule, P = 0.14). All patients experienced TAAEs, and the two dosing schedules showed similar incidence in TAAEs of grade ≥3 (100% vs 70% for 750 vs 500 mg, P = 0.21). However, the frequency of TAAEs was much higher in the 750-mg schedule (26.8 ± 6.5 vs 18.1 ± 6.5 in any grades, P = 0.01; 5.2 ± 3.0 vs 1.6 ± 1.3 in grade ≥3, P < 0.01).. Within six cycles of follow-up, the 500-mg starting dose protocol might be less toxic than the 750-mg protocol, whereas the efficacy was similar between the two dosages.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Agents; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Iodine Radioisotopes; Male; Middle Aged; Pilot Projects; Prognosis; Pyridines; Radiation Tolerance; Thyroid Neoplasms

Apatinib has been proved to be effective and safe among patients in gastric cancer in Phase II and III Trials. We aimed to evaluate its efficacy and safety in real world practice, and to explore factors associated with efficacy. Between January 2015 and February 2017, totally 36 patients with advanced gastric adenocarcinoma or adenocarcinoma of gastroesophageal junction (GEJ) were enrolled and followed up retrospectively after failing at least two lines of systemic therapy. The mPFS was 2.65 months (95%CI 1.66-3.54), and mOS was 5.8 months (95%CI 4.77-6.83). Two patients achieved partial response, and nineteen achieved stable disease. The disease control rate (DCR) was 58.3%, and objective response rate (ORR) was 5.6%. Common grade adverse events were hypertension (38.9%), proteinuria (36.1%), and neutropenia (33.3%). And the most common adverse events over grade 3 were hand-foot syndrome (8.3%), anemia (5.6%), and diarrhea (5.6%). No treatment-related death was documented during the drug administration. Exploratory analyses indicated patients treated with antiangiogenic therapy previously were more likely to benefit from apatinib.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Disease-Free Survival; Esophagogastric Junction; Female; Humans; Male; Middle Aged; Pyridines; Stomach Neoplasms

There is currently no standard treatment strategy for patients with advanced metastatic gastric cancer experiencing progression after two or more lines of chemotherapy. We assessed the efficacy and safety of apatinib, a novel vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor, in patients with advanced gastric or gastroesophageal junction adenocarcinoma for whom at least two lines of prior chemotherapy had failed.. This was a randomized, double-blind, placebo-controlled phase III trial. Patients from 32 centers in China with advanced gastric or gastroesophageal junction adenocarcinoma, for whom two or more prior lines of chemotherapy had failed, were enrolled. Patients were randomly assigned to oral apatinib 850 mg or placebo once daily. The primary end points were overall (OS) and progression-free survival (PFS).. Between January 2011 and November 2012, 267 patients were enrolled. Median OS was significantly improved in the apatinib group compared with the placebo group (6.5 months; 95% CI, 4.8 to 7.6 v 4.7 months; 95% CI, 3.6 to 5.4; P = .0149; hazard ratio, 0.709; 95% CI, 0.537 to 0.937; P = .0156). Similarly, apatinib significantly prolonged median PFS compared with placebo (2.6 months; 95% CI, 2.0 to 2.9 v 1.8 months; 95% CI, 1.4 to 1.9; P < .001; hazard ratio, 0.444; 95% CI, 0.331 to 0.595; P < .001). The most common grade 3 to 4 nonhematologic adverse events were hand-foot syndrome, proteinuria, and hypertension.. These data show that apatinib treatment significantly improved OS and PFS with an acceptable safety profile in patients with advanced gastric cancer refractory to two or more lines of prior chemotherapy.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Double-Blind Method; Drug Administration Schedule; Drug Resistance, Neoplasm; Esophageal Neoplasms; Esophagogastric Junction; Hand-Foot Syndrome; Humans; Hypertension; Kaplan-Meier Estimate; Male; Middle Aged; Proteinuria; Pyridines; Quality of Life; Receptors, Vascular Endothelial Growth Factor; Self Report; Stomach Neoplasms; Treatment Outcome

Our aim was to describe our experience in using apatinib as treatment for radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC).. Forty-seven patients undergoing apatinib treatment for RAIR-DTC were prospectively enrolled in this study. The study endpoints were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and rate of adverse events.. No patients achieved complete response, while 36 (76.6%) and 8 (17.0%) patients achieved partial response and stable disease, respectively. The ORR and DCR were 76.6% and 93.6%, respectively. The median PFS and OS were 18 and 59 months, respectively. A total of 91 adverse events occurred, of which 21 were graded as grade 3 or higher. There were no drug-related deaths.. Apatinib has distinct anti-RAIR-DTC efficacy in terms of ORR, PFS, and OS and has a favorable safety profile. It is a feasible treatment option for RAIR-DTC.

Topics: Adenocarcinoma; Antineoplastic Agents; Feasibility Studies; Humans; Iodine Radioisotopes; Pyridines; Thyroid Neoplasms

Topics: Adenocarcinoma; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; China; Early Detection of Cancer; Esophagogastric Junction; Humans; Outcome Assessment, Health Care; Paclitaxel; Progression-Free Survival; Protein Kinase Inhibitors; Pyridines; Ramucirumab; Randomized Controlled Trials as Topic; Stomach Neoplasms; Treatment Outcome; Tubulin Modulators; Vascular Endothelial Growth Factor Receptor-2

Apatinib is an oral anti-angiogenic drug, its efficacy and prognosis in cervical carcinoma are unclear. This study evaluates the effectiveness and prognostic factors of apatinib in the treatment of recurrent or advanced cervical carcinoma.. Patients with recurrent or advanced cervical cancer, who agreed to take apatinib, were recruited into this single-center and retrospective study, and administrated apatinib with or without combination of chemo- or radio-therapy until progressive disease (PD) or unacceptable toxicity.. From March 2017 to February 2019, 53 patients were reviewed. Among them, 2 (3.77%) patients occurred complete response, 16 (30.19%) patients showed partial response, 27 (50.95%) patients had stable disease, and 8 (15.09%) patients had PD. The objective response rate and disease control rate (DCR) of these patients were 33.96% and 84.91%, respectively. The DCR of patients younger than 50, nonsquamous carcinoma, first-line apatinib therapy, combined radiotherapy, lesions within radiation field, surgical history, and Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 were significantly higher than other patients (p < 0.05). The median progression-free survival (PFS) and overall survival (OS) were 6.0 months (95% CI: 4.43-7.57) and 8.0 months (95% CI: 6.52-9.48), respectively. The univariable and multivariable analysis showed that the patients with an ECOG performance status score of 2 and further line therapy were associated with poor prognosis in both PFS and OS (PFS: HR =8.35, p = 0.000; HR =6.66, p = 0.001; OS: HR = 7.40, p = 0.000; HR = 3.24, p = 0.039), respectively. The most common adverse effects (AEs) were hand-foot syndrome (35.58%), hypertension (18.87%) and fatigue (15.09%). No grade 3 AEs and drug-related death occurred.. The efficacy and prognosis of patients who are in good general condition and first-line apatinib combination therapy may be better than other patients. But further phase III clinical trials should be taken to prove this hypothesis.

Topics: Adenocarcinoma; Analysis of Variance; Angiogenesis Inhibitors; Antineoplastic Agents; Carcinoma, Squamous Cell; Combined Modality Therapy; Fatigue; Female; Hand-Foot Syndrome; Humans; Hypertension; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Progression-Free Survival; Pyridines; Treatment Outcome; Uterine Cervical Neoplasms

This study aimed to compare the therapeutic effects between apatinib combined chemotherapy and chemotherapy alone as second-line or above therapy in advanced gastric cancer (GC) or adenocarcinoma of the gastroesophageal junction (AGEJ). The clinical data of advanced GC or AGEJ patients, including sex, age, Eastern Cooperative Oncology Group (ECOG) grading, chemotherapy regimen, pathological grading, location of primary lesion, previous gastrectomy, metastases, previous chemotherapy or radiotherapy were retrospectively collected, and the progression-free survival (PFS) was recorded. 127 patients underwent apatinib combined chemotherapy and 60 patients underwent chemotherapy regimen alone. Disease control rate (DCR) of patients with apatinib combined chemotherapy was higher than that of chemotherapy alone (P=0.033). A Kaplan-Meier (KM) plot showed that PFS was significantly longer in patients receiving apatinib combined chemotherapy than those treated by chemotherapy alone (P = 0.002). The PFS of patients with a number of metastatic lesions ≤ 2 was obviously longer than that of patients with a number of metastatic lesions > 2 (P < 0.001). Cox regression analysis revealed that PFS was independently associated with the number of metastatic lesions >2 (HR=2.129, 95% CI: 1.256-3.608, P=0.005) and treatment methods (chemotherapy alone or apatinib combined chemotherapy) (HR=1.427, 95% CI: 1.055-1.930, P=0.021). Compared with chemotherapy alone, apatinib combined chemotherapy could significantly improve DCR and prolong the PFS in advanced GC or AGEJ cases who had failed in at least first-line chemotherapy with acceptable tolerance.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Esophagogastric Junction; Female; Humans; Male; Middle Aged; Neoplasm Grading; Progression-Free Survival; Pyridines; Retrospective Studies; Stomach Neoplasms; Treatment Outcome

As a small-molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), apatinib has shown a survival benefit in multiple solid tumors. This study aims to evaluate the efficacy and safety of apatinib in patients with metastatic, recurrent cervical cancer after failure of radiotherapy and first-line chemotherapy.. A total of 42 patients between June 2018 and March 2019 were involved in this study. All patients orally received apatinib once daily in a 4-week cycle until disease progression or adverse events that prohibit further therapy. The primary endpoint was progression-free survival (PFS), the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), health-related quality of life (HRQoL) and adverse events.. During a median follow-up of 13 months, 8 patients achieved a partial response and 24 cases achieved stable disease. None of them reported a complete response. The ORR and DCR were 19.0 and 76.2%, respectively. The median PFS was 6.0 months (95% CI 4.9-7.1), and the median OS was 12.0 months (95% CI 10.1-13.9). The global health score/HRQoL improved significantly following 3-cycle treatment (50.4 ± 12.5 vs. 60.1 ± 11.8; p < 0.01). The most frequent grade 3-4 adverse events were hand-foot syndrome, hypertension and fatigue.. Apatinib should be an effective and tolerable treatment option for patients with metastatic, recurrent cervical cancer after failure of radiotherapy and first-line chemotherapy.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Agents; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Female; Hand-Foot Syndrome; Humans; Hypertension; Middle Aged; Neoplasm Recurrence, Local; Progression-Free Survival; Prospective Studies; Protein Kinase Inhibitors; Pyridines; Quality of Life; Survival Rate; Treatment Outcome; Uterine Cervical Neoplasms

Topics: Adenocarcinoma; Antineoplastic Agents; Humans; Hypothyroidism; Lung Neoplasms; Pyridines; Rectal Neoplasms

Apatinib (Jiangsu HengRui Medicine Co. Ltd), a vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase inhibitor, has been proven to be safe and to significantly prolong survival in advanced chemotherapy-refractory gastric cancer. This study aimed to assess and compare the efficacy and safety of apatinib combined with chemotherapy with that of chemotherapy alone as second- or higher-line treatment in patients with advanced and metastatic gastric or those with metastatic gastroesophageal junction adenocarcinoma (mGC).Patients with chemotherapy-refractory mGC at Jiangsu Cancer Hospital & Research Institute were prospectively enrolled and assigned into 2 groups at a 2:1 ratio. The first group (combination group) comprised patients with combination treatment (apatinib + chemotherapy), while the second group comprised patients treated with chemotherapy alone (chemotherapy group). The dose of apatinib was 500 mg/d, and the chemotherapy regimens were based on fluoropyrimidine, platinum, and paclitaxel or irinotecan. The primary end points were progression-free survival (PFS).Between November 2014 and December 2016, 175 patients were enrolled. PFS was significantly improved in the combination group compared with that in the chemotherapy group (8.5 months [95% confidence interval [CI], 6.45-10.54] vs 7.0 months [95% CI, 5.12-8.88] P = .021; hazard ratio (HR): 0.645 [95% CI: 0.429-0.969] P = .035). The disease control rate (DCR) was also higher in the combination group than that in the chemotherapy group (58.4% vs 41.9%, P = .041). Moreover, the incidence of Grade 3 to 4 hand-foot syndrome, proteinuria, and hypertension was significantly different between the 2 groups. Combined therapy (P = .040) and metastatic sites <2 (P = .008) were the independent prognostic factors for disease progression.Compared with chemotherapy alone, the addition of apatinib to chemotherapy could better improve PFS and DCR with an acceptable safety profile for mGC refractory to 1 or more line of prior chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Female; Hand-Foot Syndrome; Humans; Hypertension; Male; Middle Aged; Neoplasm Metastasis; Prospective Studies; Protein Kinase Inhibitors; Proteinuria; Pyridines; Stomach Neoplasms; Vascular Endothelial Growth Factor Receptor-2

Dual‑specificity phosphatase‑1 (DUSP1) is an oncogene that is associated with cancer progression following drug resistance. In order to investigate the potential relationship between DUSP1 and apatinib resistance in gastric cancer cells, we preformed many assays to study this problem. DUSP1 gene was detected by RT‑qPCR assay, proteins in MAPK pathway were quantified by western blot assay, and CCK‑8 assay, flow cytometry and Hoechest 33342 stain were performed to detect the resistance of cells, cell cycles and apoptosis, respectively. Immunohistochemical staining was used to discover the expression of DUSP1 protein in patients' tumor or paratumor tissues. It was found that apatinib (Apa)‑resistant gastric cancer (GC) cells showed increased expression of DUSP1, whereas the knockdown of DUSP1 in resistant cells resensitized these cells to Apa. The restored sensitivity to Apa was the result of inactivation of mitogen‑activated protein kinase (MAPK) signaling and the induction of apoptosis. The in vitro use of Apa in combination with a DUSP1 inhibitor, triptolide, exerted significant effects on inhibiting the expression of DUSP1, growth inhibition, and apoptosis via the inactivation of MAPK signaling. In patients who did not undergo chemotherapy or targeted therapy, the expression of DUSP1 in adjacent tissues was higher when compared with that observed in tumor tissues. In addition, the expression of DUSP1 was higher in the early stages of GC than in the advanced stages. The expression of DUSP1 in tumor tissues was not associated with the survival rate of the patients. Therefore, increased expression of DUSP1 may be responsible for Apa resistance, and DUSP1 may serve as a biomarker for Apa efficacy. In conclusion, inducing the downregulation of DUSP1 may be a promising strategy to overcome Apa resistance.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Apoptosis; Case-Control Studies; Cell Cycle; Cell Proliferation; Drug Resistance, Neoplasm; Dual Specificity Phosphatase 1; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Middle Aged; Mitogen-Activated Protein Kinases; Prognosis; Pyridines; Signal Transduction; Stomach Neoplasms; Tumor Cells, Cultured

The Rearranged during transfection (RET) fusion gene is a newly identified oncogenic mutation in non-small cell lung cancer (NSCLC). The aim of this study is to explore the biological functions of the gene in tumorigenesis and metastasis in RET gene fusion-driven preclinical models. We also investigate the anti-tumor activity of Apatinib, a potent inhibitor of VEGFR-2, PDGFR-β, c-Src and RET, in RET-rearranged lung adenocarcinoma, together with the mechanisms underlying. Our results suggested that KIF5B-RET fusion gene promoted cell invasion and migration, which were probably mediated through Src signaling pathway. Apatinib exerted its anti-cancer effect not only via cytotoxicity, but also via inhibition of migration and invasion by suppressing RET/Src signaling pathway, supporting a potential role for Apatinib in the treatment of KIF5B-RET driven tumors.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Apoptosis; Carcinogenesis; Cell Line, Tumor; Cell Movement; Female; Humans; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Metastasis; Oncogene Proteins, Fusion; Proto-Oncogene Proteins c-ret; Pyridines; Signal Transduction; src-Family Kinases; Xenograft Model Antitumor Assays

Alpha-fetoprotein (AFP) is an important marker for hepatocellular carcinoma, and the detection of serum AFP is currently the principle method for the diagnosis of hepatocellular carcinoma. The prevalence of gastric cancer (GC) with high level of serum AFP is extremely rare, but has unique clinical features.. We herein present a rare case with GC and high level of serum AFP. A 64-year-old Chinese female underwent gastrectomy was diagnosed as gastric adenocarcinoma and the pathological stage was T1bN0M0, IA. With the progression of disease, the tumor widely metastasized and the serum AFP level increased progressively with the highest level of 3396 ng/mL. She successively entered into 3 lines palliative systematic chemotherapy and fourth-line targeted therapy of apatinib, a small molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2. Although previous studies suggested that the prognosis of this special type of GC was poor, this patient lived for 22 months after tumor transfer. Apatinib kept her progression-free survival for 5 months, and the overall survival was 4.5 years.. So, we speculate that maybe we can focus apatinib on serum AFP elevated GC patients.

Topics: Adenocarcinoma; alpha-Fetoproteins; Female; Gastrectomy; Humans; Middle Aged; Molecular Targeted Therapy; Pyridines; Stomach Neoplasms; Vascular Endothelial Growth Factor Receptor-2