s-1-(combination) and Adenocarcinoma-of-Lung

A 62-year-old male was diagnosed with large cell lung cancer(c-Stage IV)based on pathological examination of an anterior chest tumor. He received chemotherapy with cisplatin, pemetrexed, and bevacizumab. He suffered from persistent hiccups from day 2 of the first course of chemotherapy. He was unsuccessfully treated with chlorpromazine, shakuyakukanzoto, and gabapentin. Therefore, we administered pregabalin to him, and his hiccups subsided immediately. To prevent hiccups, he subsequently took pregabalin along with his chemotherapy regimen, and was able to receive 4 courses of chemotherapy without persistent hiccups. Pregabalin is a possible therapeutic option for treating persistent chemotherapy-induced hiccups.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Hiccup; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pregabalin; Tegafur; Treatment Outcome

Although cytotoxic chemotherapy is essential in epidermal growth factor receptor (EGFR)‑mutated non‑small cell lung cancer (NSCLC), it is unclear which regimen is most effective. We retrospectively compared the efficacy of standard platinum‑based chemotherapy with that of combination chemotherapy using vinorelbine (VNR) plus dihydropyrimidine dehydrogenase‑inhibitory fluoropyrimidine (DIF) in EGFR‑mutated lung adenocarcinomas, and we investigated a potential mechanism by which the combination chemotherapy of VNR + DIF was favorable in the treatment of EGFR‑mutated lung adenocarcinoma in vitro. In our retrospective analysis, the response rate and disease control rate afforded by the VNR + DIF treatment tended to be better than those by platinum‑based chemotherapy, and the progression‑free survival of the 24 VNR + DIF‑treated patients was significantly longer than that of the 15 platinum‑based chemotherapy patients. In EGFR‑mutated PC9 cells, VNR induced EGFR dephosphorylation at a clinically achievable concentration. 1BR3‑LR cells, a line of fibroblast cells transfected with a mutant EGFR construct, were completely resistant to gefitinib in the medium containing 10% fetal bovine serum (FBS), whereas the sensitivity of these cells to gefitinib was increased in 0.5% FBS‑containing medium. Similarly, the sensitivity of 1BR3‑LR cells to VNR was increased when they were cultured in low‑serum condition. In addition, sodium orthovanadate (Na3VO4) inhibited the EGFR dephosphorylation induced by VNR or gefitinib and suppressed the cell growth inhibition by these agents in PC9 cells. VNR and gefitinib showed synergistic cell growth inhibition in combination with 5‑fluorouracil (5‑FU) in PC9 cells. We propose that the EGFR dephosphorylation induced by VNR is related to cell growth inhibitory activity of VNR, and that this is one of the mechanisms of the synergistic effect of VNR + 5‑FU in EGFR‑mutated lung cancer cells. In conclusion, the combination chemotherapy of VNR + DIF may be a promising treatment for NSCLC patients with EGFR mutations.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; ErbB Receptors; Female; Fluorouracil; Gefitinib; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Mutation; Oxonic Acid; Quinazolines; Retrospective Studies; Tegafur; Treatment Outcome; Vinblastine; Vinorelbine

A phase I dose-escalation study was performed to investigate the safety and pharmacokinetics of the combination of S-1 and gefitinib in patients with pulmonary adenocarcinoma who had failed previous chemotherapy.. Patients received gefitinib at a fixed daily oral dose of 250 mg, and S-1 was administered on days 1-14 every 21 days at doses starting at 60 mg/m(2) (level 1) and escalating to 80 mg/m(2) (level 2). The primary end point of the study was determination of the recommended dose for S-1 given in combination with a fixed dose of gefitinib.. Twenty patients were enrolled in the study. Two of the first six patients at dose level 2 experienced a dose-limiting toxicity (elevation of alkaline phosphatase of grade 3 in one patient; elevations of aspartate and alanine aminotransferases of grade 3 in the other). The recommended dose was thus determined as level 2, and an additional 11 patients were assigned to this level. All observed adverse events were well managed. The response rate was 50 % (10 of 20 patients), and the median progression-free survival (PFS) and overall survival times were 10.5 and 21.2 months, respectively. In EGFR mutation-positive patients (n = 9), seven patients achieved an objective response and the median PFS was 12.4 months, whereas none with wild-type EGFR (n = 6) responded. No pharmacokinetic interaction between S-1 and gefitinib was detected.. The combination of S-1 and gefitinib is well tolerated and appears to possess activity against EGFR mutation-positive NSCLC.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Gefitinib; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Quinazolines; Tegafur

Adjuvant chemotherapy with platinum-based regimens for completely resected early-stage non-small cell lung cancer (NSCLC) provides overall survival benefit in several clinical trials.. We conducted this prospective study to evaluate the efficacy and safety of adjuvant chemotherapy with carboplatin and S-1 for patients with completely resected stage II to IIIA NSCLC.. Patients with completely resected stage IIA to IIIA NSCLC were treated with four cycles of carboplatin with area under the concentration time curve of 5 mg/mL/min on day 1 plus S-1 at 80-120 mg/bodyweight per day for two weeks, followed by one-week rest as adjuvant chemotherapy. The primary endpoint was the completion rate of three cycles of the treatment. The secondary endpoints were safety and two-year survival rate.. A total of 19 patients were enrolled, until the study was terminated prematurely because of fatal pulmonary embolism in two patients. The median number of treatment cycles was three (range: 1-4). The completion rate of three cycles was 78.9% (95% confidence interval [CI]: 56.6-91.4%). Two-year disease-free survival rate was 57.8%. Grade 3 or 4 hematological toxicities included neutropenia (26.2%), anemia (5.2%), and thrombocytopenia (15.7%). Grade 3 or 4 nonhematological toxicities were anorexia (10.5%) and nausea (10.5%). Febrile neutropenia developed in 5.2%. In two patients (10.5%), grade five pulmonary embolism was observed, and the causal relationship with treatment could not be denied.. Carboplatin and oral S-1 had modest survival benefit, but this regimen was not tolerable in an adjuvant setting because fatal pulmonary embolism occurred in two patients.. Carboplatin and oral S-1 had modest survival benefit but this regimen was not tolerable. Fatal pulmonary embolism occurred in this regimen.

Topics: Adenocarcinoma of Lung; Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pilot Projects; Prospective Studies; Survival Rate; Tegafur

Herein, we report a case of unresectable lung cancer in which S-1 monotherapy contributed to an improvement in the patient's quality of life and to prolonged survival. A 44-year-old man with primary pulmonary adenocarcinoma(negative driver mutation and a PD-L1 tumor proportion score of 1-24%)of clinical stage ⅢA(cT4N0M0)underwent multidisciplinary treatment as follows: 1 ) weekly carboplatin and paclitaxel plus radiotherapy as induction chemoradiotherapy, 2 ) surgery that revealed that the lesion was unresectable, 3 ) cisplatin plus pemetrexed as second-line treatment, and 4 ) pembrolizumab as third-line treatment. However, the disease progressed after 19 courses of pembrolizumab, and the patient developed cachexia due to esophageal stenosis caused by tumor enlargement. He underwent percutaneous gastrostomy and was fed via a gastrostomy tube. S-1 monotherapy(2-week administration every 3 weeks)was introduced as fourth-line treatment. After 3 courses of S-1 monotherapy, the patient complained of regurgitation of stomach fluid. Computed tomography( CT)revealed that the primary tumor had decreased in size, and he developed the ability to drink water. After 6 courses of S-1, CT revealed progressive disease, so atezolizumab was administered as fifth-line treatment. However, after 2 courses, mediastinitis due to esophageal penetration into the mediastinum occurred. The patient died 28 months after the initial treatment.

Topics: Adenocarcinoma of Lung; Adult; Antimetabolites, Antineoplastic; Drug Combinations; Humans; Lung Neoplasms; Male; Oxonic Acid; Quality of Life; Tegafur

Topics: Adenocarcinoma of Lung; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Docetaxel; Drug Combinations; Humans; Lung Neoplasms; Male; Oxonic Acid; Paget Disease, Extramammary; Pneumonectomy; Positron-Emission Tomography; Skin Neoplasms; Tegafur; Treatment Outcome

A 62-year-old Japanese female with primary lung adenocarcinoma received seven cycles of nivolumab as an eighth line of chemotherapy until she presented with hemoptysis. After transcatheter arterial embolization therapy, she received subsequent chemotherapy with paclitaxel and S-1. Four weeks later, a chest computed tomography examination revealed infiltrative shadows mainly in the right lung field, in addition to enlargement of the lung metastasis in the right middle lung lobe. Bronchofiberscopic examination revealed infiltration of lymphocytes without any malignant cells in the right segment 1 of the lung, which suggested interstitial lung disease. Corticosteroid therapy not only improved the infiltrative shadows but also reduced the lung metastasis. Even after the infiltrative shadows improved, the lung metastasis reduced further. This phenomenon resembles manifestation of pseudoprogression during treatments with immune checkpoint inhibitors, such as nivolumab.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Antibodies, Monoclonal; Drug Combinations; Female; Humans; Lung; Lung Neoplasms; Middle Aged; Neoplasm Metastasis; Nivolumab; Oxonic Acid; Paclitaxel; Tegafur; Tomography, X-Ray Computed

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Adult; Anaplastic Lymphoma Kinase; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Cell Cycle Proteins; Drug Combinations; Glutamates; Guanine; Humans; Lung Neoplasms; Male; Microtubule-Associated Proteins; Oxonic Acid; Pemetrexed; Positron-Emission Tomography; Receptor Protein-Tyrosine Kinases; Serine Endopeptidases; Tegafur; Treatment Outcome