s-1-(combination) and apatinib

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

Small cell carcinoma of the esophagus (SCCE) is an uncommon but lethal disease characterized by dismal prognosis. Only 10% of advanced SCCE patients survive longer than 1 year. Resection is a choice for limited-stage cases, whereas the optimal treatment regimen for primary SCCE is yet to be elucidated. To the best of our knowledge, the efficacy of S-1 plus apatinib for irinotecan-refractory SCCE has not been reported before.. A 61-year old, previously healthy male was admitted for dysphagia and fatigue. Endoscopic biopsy revealed a tumor in the middle third of the esophagus. Further exams including abdomen computed tomography excluded distant metastasis.. Primary SCCE (pT1bN1M0, IIB) was established after salvage operation.. The tumor was enlarged after 1 cycle of first-line chemotherapy using irinotecan plus cisplatin, which indicated drug resistance. Second-line oral apatinib (425 mg daily) plus S-1 (60 mg, twice daily for 4 weeks with a 2-week drug-free interval) for a month showed efficacy, as shown by decreased serum neuron-specific enolase and stable of the esophageal lesion. Thereafter, salvage minimally invasive Ivor-Lewis esophagectomy and 2-field lymph node dissection was performed, followed by oral apatinib plus S-1 at the prior dosage for 6 months. In addition, maintenance therapy using low-dose apatinib (250 mg daily) plus S-1 (40 mg, twice daily for 4 weeks with a 2-week interval) were administered for another 6 months. Then the patient was followed up irregularly at the outpatient clinic.. The adverse events including hand-foot syndrome, hypertension, vomiting, leukopenia, impaired hepatic function, and fatigue were mainly tolerable. Forty months after the operation, he was readmitted for back pain and disseminated bone metastases appeared in magnetic resonance images. His progression-free survival could not be obtained precisely, and his overall survival was longer than 40 months up to September 2019.. S-1 plus apatinib followed by a timely esophagectomy with curative intent might be an alternative option for chemotherapy-refractory SCCE in selected patients. Better evidence is warranted.

Topics: Antimetabolites, Antineoplastic; Carcinoma, Small Cell; Drug Combinations; Drug Resistance, Neoplasm; Drug Therapy, Combination; Esophageal Neoplasms; Esophagectomy; Humans; Irinotecan; Male; Middle Aged; Oxonic Acid; Protein Kinase Inhibitors; Pyridines; Salvage Therapy; Tegafur

Apatinib-targeted therapy is considered a promising treatment option for malignancies. This study systematically evaluated the efficacy and safety of the combination of apatinib and S-1 for the treatment of patients with advanced gastric cancer (GC).. Clinical trials were searched from the PubMed, Cochrane Library, Embase, CNKI, and Wanfang databases. Outcome measures including therapeutic efficacy, quality of life (QoL), and adverse events were extracted and evaluated.. Data from 8 trials including 393 patients with advanced GC were included. The results indicated that, compared with S-1 alone, the combination of apatinib with S-1 significantly improved patient partial response rate (odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.21-3.02, P = .005), overall response rate (ORR, OR = 2.40, 95% CI = 1.51-3.82, P = .0002), and disease control rate (DCR, OR = 2.78, 95% CI = 1.51-5.10, P = .0010), whereas the rates of complete response (CR, OR = 2.38, 95% CI = 0.93-6.12, P = .07) and stable disease (SD, OR = 0.99, 95% CI = 0.64-1.54, P = .97) and QoL (OR = 1.22, 95% CI = 0.51-2.92, P = .66) did not differ significantly. Moreover, the group receiving the combined therapy had higher rates of hand-foot syndrome (OR = 2.23, 95% CI = 1.19-4.17, P = .01), hypertension (OR = 8.85, 95% CI = 4.07-19.26, P < .00001), albuminuria (OR = 11.25, 95% CI = 3.32-38.06, P = .0001), and hemoglobin reduction (OR = 3.19, 95% CI = 1.32-7.67, P = .010), whereas analysis of other adverse events did not show significant differences (P > .05).. The combination of apatinib and S-1 is more effective for GC treatment than S-1 alone. However, this combined treatment could lead to increased hand-foot syndrome, hypertension, albuminuria, and hemoglobin reduction. Therefore, the benefits and risks should be considered before treatment.

Topics: Antineoplastic Agents; China; Drug Combinations; Drug Therapy, Combination; Humans; Neoplasm Staging; Oxonic Acid; Pyridines; Randomized Controlled Trials as Topic; Stomach Neoplasms; Tegafur; Treatment Outcome

We conducted a single-arm phase II trial to investigate the short-term efficacy and safety of apatinib combined with oxaliplatin and S-1 in the treatment of unresectable gastric cancer.. Previously untreated patients with unresectable HER-2-negative advanced gastric cancer were selected. All the patients received six cycles of S-1 and oxaliplatin and five cycles of apatinib, which were administered at intervals of three weeks. The surgery was performed after six cycles of drug treatment. The primary endpoints were radical resection (R0) rate and safety. This study was registered with the China Trial Register, number ChiCTR-ONC-17010430  (01/12/2016-01/12/2022).. A total of 39 patients were enrolled. Efficacy evaluation was feasible for 37 patients. One patient achieved complete response (CR, 2.7%), 26 patients achieved partial response (PR, 70.3%), three patients had stable disease (SD, 8.1%) and seven patients had progressive disease (PD, 18.9%). The objective response rate (ORR) was 73.0% and the disease control rate (DCR) was 81.1%. 22 patients underwent surgery, among which 14 patients underwent radical resection (R0), with a R0 resection rate of 63.6%. The 1-year survival rate of the surgical group (22 patients) was 71.1% and the 2-year survival rate was 41.1%. The median survival time was 21 months. The incidence of adverse events (AEs) was 100%. Leucopenia (65.3%) and granulocytopenia (69.2%) were the most common hematological AEs. The most common non-hematological AEs were fatigue (51.3%) and oral mucositis (35.9%).. Apatinib combined with oxaliplatin and S-1 showed good short-term survival and acceptable safety in the conversion therapy of unresectable gastric cancer.

Topics: Adult; Aged; Drug Combinations; Female; Humans; Male; Middle Aged; Oxaliplatin; Oxonic Acid; Pyridines; Stomach Neoplasms; Survival Analysis; Tegafur

Background Esophageal cancer is a very common malignant tumor in China, especially esophageal squamous cell carcinoma (ESCC), but there is currently no effective treatment for patients after first-line chemotherapy failure. Apatinib has shown promising outcomes in treatment with various solid tumors. Objectives To evaluate the clinical efficacy and safety of apatinib combined with S-1 in the treatment of advanced ESCC patients after first-line chemotherapy failure. Methods In this prospective study, fifteen patients with advanced ESCC who failed first-line chemotherapy were enrolled from Nov 2016 to Apr 2019. Patients received the combination therapy with apatinib (250-500 mg, once daily) plus S-1 (40-60 mg based on body surface area, twice daily). Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), disease control rate (DCR) and objective response rate (ORR). Adverse events (AEs) were recorded to evaluate the safety. Results A total of 12 patients were included in the efficacy analysis. The median PFS was 6.23 months, and the median OS was 8.83 months. Two (16.67%) patients achieved partial remission, 9 patients (75.00%) achieved stable disease and 1 (8.33%) patient achieved progressive disease. DCR and ORR was 91.67%and 16.67%, respectively. Most frequent AEs were hypertension, myelosuppression, weakness, hemorrhage, hand-foot syndrome, total bilirubin elevation, sick, proteinuria, oral ulcer, loss of appetite, and transaminase elevation. The most AEs were in grade I~II. Conclusion The combination therapy of apatinib plus S-1 was effective and well tolerated in the treatment of advanced ESCC patients after first-line chemotherapy failure. The combination therapy has the potential to be a potent therapeutic option for advanced ESCC patients after first-line chemotherapy failure.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; Male; Middle Aged; Oxonic Acid; Protein Kinase Inhibitors; Pyridines; Survival Analysis; Tegafur; Treatment Outcome

Squamous cell lung cancer is one of the major pathological types in patients with non-small cell lung cancer. Since treatment with angiogenic agents and target drugs in patients with advanced squamous cell lung cancer is not promising, there are limited strategies to improve the outcome in such patients. Herein, we report a pretreated patient with advanced squamous cell lung cancer, who received low-dose of apatinib combined with S-1 as salvage treatment, with good long-term response.. The patient complained of dry cough for one month without any relief by medication. Otherwise, she denied any other medical or family history.. According to the chest computed tomography, and pathologic findings from biopsy for lesion in lung, the patient was diagnosed with lung squamous cell lung cancer with enlargement of bilateral supraclavicular lymph nodes suggesting metastasis, staged as IIIb.. The patient received gemcitabine plus cisplatin as first line treatment, and gemcitabine as maintenance therapy. After progression, she received vinorelbine as second line treatment. After progression again, she received low-dose apatinib combined with S-1 as third line treatment.. With the follow-up period from October 21, 2014, to April 6, 2019, there were 15 months, 9 months, and 24 months of progression-free survival time for first line (including maintenance therapy), second line, and third line treatment, respectively. The only adverse event was neutropenia at grade 2 (CTC AE) occurring during the maintenance treatment.. This case indicated that low-dose apatinib combined with S-1 might be effective and safe in selected pretreated patients with advanced squamous cell lung cancer. It might be worthy to conduct further researches to investigate the efficacy and safety of the combination therapy in such patients.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Disease Progression; Drug Combinations; Female; Humans; Lung Neoplasms; Middle Aged; Oxonic Acid; Pyridines; Tegafur

A substantial number of patients with esophageal squamous cell carcinoma (ESCC) do not achieve complete remission after definitive concurrent chemoradiotherapy (dCRT). We performed this retrospective study to evaluate the efficacy and safety of apatinib combined with S-1/capecitabine as the oral maintenance therapy for these patients.. Thirty-nine ESCC patients with residual disease after dCRT were included. Patients were treated with apatinib combined with S-1 /capecitabine after dCRT. Efficacy, toxicity, and survival were analyzed.. Of the 39 patients, 5 (12.8%) achieved a partial response and 29 (74.4%) achieved stable disease, yielding a disease control rate of 87.2%. The median progression-free survival (PFS) and overall survival (OS) were 27.5 (95%CI: 14.9 - 40.1) and 38.1 (95%CI: 31.3 - 44.8) months. Most frequent adverse events were of grade 1 to 2. Multivariate analysis revealed the occurrence of any adverse events (HR = 0.274, 95%[CI] = 0.119 - 0.630) correlated to better PFS and occurrence of proteinuria (HR = 0.108, 95%[CI] = 0.025 - 0.456) predicted better OS.. The oral combination therapy consisting of apatinib and S-1/capecitabine showed a tolerable toxicity profile and achieved satisfactory disease control in ESCC patients with residual disease after dCRT.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Drug Combinations; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; Maintenance Chemotherapy; Male; Middle Aged; Oxonic Acid; Pyridines; Retrospective Studies; Tegafur

Advanced gastric cancer (AGC) patients are not tolerant to the toxicities of traditional chemotherapy and its second-line therapeutic regimens are limited. The aim of the present study is to evaluate the efficacy and safety of apatinib combined with S-1 as the second-line therapy for AGC patients.Patients with AGC were enrolled in this study. Patients received oral apatinib (250 mg to 500 mg once daily) and S-1(40 mg/m2 twice daily) on days 1-14. Each cycle was 28 days and one course of treatment consisted of 2 cycles. Clinical efficacy and adverse events (AEs) were observed. Kaplan-Meier method was used for survival analysis.From November 2015 to December 2017, 58 AGC patients who failed first-line chemotherapy were enrolled and assessed retrospectively. According to the Response Evaluation Criteria in Solid Tumors (RECIST) standard, all patients were evaluable for response. None achieved CR, and 10 (17.2%) achieved PR (95% CI 7.2%-27.3%). SD was observed in 58.6% (34/58) of patients (95% CI 45.6%-71.7%) and NR in 24.1% (14/58) of patients (95% CI 12.8%-35.5%). The objective response rate (ORR) and the disease control rate (DCR) were 17.2% and 75.8% respectively. The median progression-free survival (PFS) and median overall survival (OS) were 143.1 days (95% CI 121.7-164.5) and 211.6 days (95% CI 162.9-219.7) respectively. The multivariate analysis showed that the ECOG PS was the independent factor of PFS and OS for AGC patients (PFS: HR = 3.565, 95% CI: 2.25-5.65, P < .001; OS: HR = 3.676, 95% CI: 2.29-5.89, P < .001). The main AEs were fatigue (72.4%), hypertension (46.6%), and leukopenia (48.3%).Apatinib combined with S-1 showed promising efficiency and was well tolerated as the second-line therapy for AGC patients. ECOG PS was the independent factor of PFS and OS for AGC patients. AEs were moderate and controllable, and leukopenia or hypertension was predictable factors for the PFS and OS of AGC patients.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Drug Therapy, Combination; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Oxonic Acid; Progression-Free Survival; Pyridines; Response Evaluation Criteria in Solid Tumors; Retrospective Studies; Stomach Neoplasms; Tegafur; Young Adult

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, one of the novel oral antiangiogenic agents, shows survival benefits in treating advanced or metastatic gastric adenocarcinoma. However, its efficacy in treating advanced head and neck neoplasms has not been reported. Herein, three elderly men with advanced head and neck neoplasms were treated with apatinib and S-1. Their initial diagnoses were hypopharyngeal carcinoma, metastatic squamous cell carcinoma of head and neck, and squamous cell carcinoma of the pyriform sinus. All patients underwent repeated chemotherapy but developed disease progression. As they refused radiotherapy due to its serious adverse reaction, apatinib was administered at a dose of 425 mg daily and S-1 at 60 mg twice daily. Thirty days after apatinib administration, the patients achieved partial response according to the Response Evaluation Criteria in Solid Tumors 1.1 standard. Mild toxicity or drug-related side effect was observed during the treatment. Therefore, apatinib and S-1 could be the new treatment option for advanced head and neck neoplasms. However, clinical trials are required to confirm their efficacy and safety.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Biopsy; Drug Combinations; Head and Neck Neoplasms; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Pyridines; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

Brain metastasis (BM) is a rising challenge in forward-looking oncology, as its treatment choices are very limited, especially, after the failure of local treatment schemes.. We report on a 39-year-old Chinese woman who was diagnosed with stage IV triple-negative breast cancer(TNBC) with multiple brain, lung, and bone metastases. She had previously, undergone whole-brain radiation therapy. Paclitaxel, platinum, UTD1, capecitabine, gemcitabine, vinorelbine, and single-agent apatinib were then administered as first- to fifth-line therapies. She exhibited progression each time after a short period of disease stabilization.. Triple-negative breast cancer.. The patient chose treatment with apatinib+CPT-11+S-1 as the sixth-line therapy.. A remarkable response of the brain, and lung metastases, and alleviation of the brain edema were achieved, and these effects persisted for 7 months.. We describe the significant anti-tumor effect of apatinib + CPT-11 + S-1 against BMs from breast cancer. This report is the first to suggest potential approaches to BM treatment using this scheme and describes the effects of an apatinib-containing regimen on BMs.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Edema; Brain Neoplasms; Camptothecin; Disease Progression; Drug Combinations; Female; Humans; Irinotecan; Lung Neoplasms; Neoplasm Staging; Oxonic Acid; Pyridines; Tegafur; Triple Negative Breast Neoplasms