s-1-(combination) and Neoplasms--Squamous-Cell

A case showing reinforcement of the action of warfarin and potassium in a patient administered S-1 is reported.The patient was a 71-year-old man with left upper gingival cancer.He had ventricular tachycardia (VT), hypertrophic cardiomyopathy, and a cerebellar infarction.He underwent a pacemaker implantation, and was administered warfarin.After the operation, in mid-March 2010, he was administered with S-1 and warfarin. However, the international normalized ratio of prothrombin time (PT-INR) increased to an extremely high level of 5.82, and S-1 and warfarin were stopped. They were re-administered at the end of April, and the PT-INR stabilized to approximately 2.

Topics: Aged; Anticoagulants; Antimetabolites, Antineoplastic; Cardiomyopathy, Hypertrophic; Cerebral Infarction; Drug Combinations; Drug Interactions; Humans; Male; Mouth Neoplasms; Neoplasms, Squamous Cell; Oxonic Acid; Tachycardia, Ventricular; Tegafur; Warfarin

Cisplatin plus fluorouracil is widely used for the treatment of head and neck cancer. However, the cisplatin plus fluorouracil regimen necessitates hospitalization. Therefore, we planned to develop a new regimen that can be administered on an outpatient basis and performed a phase I study of S-1 + nedaplatin.. S-1 was given orally at a fixed dose for 14 days, and nedaplatin was administered intravenously on day 8 of S-1 administration. The dose of nedaplatin was increased in 10-mg/m(2) steps to find the maximum tolerated dose, depending on the appearance of dose-limiting toxicities.. A total of 14 patients were registered. The maximum tolerated dose of nedaplatin was determined to be 90 mg/m(2). The main toxicities were neutropenia and thrombocytopenia. The response rate was 57.1%.. The recommended dose of nedaplatin for a phase II study was determined to be 80 mg/m(2). We concluded that our regimen was well tolerated and that the response rate was acceptable.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Carcinoma, Squamous Cell; Cisplatin; Disease Progression; Drug Combinations; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Recurrence, Local; Neoplasms, Squamous Cell; Organoplatinum Compounds; Oxonic Acid; Squamous Cell Carcinoma of Head and Neck; Tegafur

This study aimed to evaluate the effect and safety of anlotinib combined with S-1 in the treatment of recurrent or metastatic esophageal cancer patients who refused or were intolerant to intravenous chemotherapy.This study retrospectively reviewed 22 recurrent or metastatic esophageal cancer patients who refused or were intolerant to intravenous chemotherapy between June 1, 2018 and February 28, 2019. All patients did not previously receive anlotinib or S-1.Of 22 patients, 20 patients had squamous cell cancer. Seventeen patients received at least 2 cycles of anlotinib plus S-1. The objective response rate (ORR) was 35.3%, and the disease control rate (DCR) was 82.4%. The median progression-free survival (PFS) was 3.5 months, and median overall survival (OS) was 5.2 months. In the first-line treatment subgroup, the ORR was 50%, the DCR was 80%, the median PFS was 4.5 months, and the median OS was 5.8 months. In the second-line and above treatment subgroup, the ORR was 14.3%, the DCR was 85.7%, the median PFS was 3.0 months, and the median OS was 3.7 months. The main adverse events (AEs) of anlotinib combined with S-1 were fatigue (58.8%), hypertension (47.1%), hemoptysis (29.4%), anemia (29.4%), nausea (23.5%), liver function damage (23.5%), albuminuria (17.6%), abdominal pain (17.6%), leukopenia (17.6%), neutropenia (11.8%), fever (11.8%), and hand-foot syndrome (11.8%). Grade 3 AEs included nausea (5.9%) and hypertension (5.9%), and no grade 4 or more AEs were reported.Anlotinib combined with S-1 achieved promising disease control and satisfactory survival with tolerable safety in recurrent metastatic esophageal cancer who refused or were intolerant to intravenous chemotherapy.

Topics: Antimetabolites, Antineoplastic; Drug Combinations; Esophageal Neoplasms; Humans; Indoles; Neoplasm Recurrence, Local; Neoplasms, Squamous Cell; Oxonic Acid; Quinolines; Retrospective Studies; Tegafur; Treatment Outcome

We reported previously that decorin (DCN) is significantly up-regulated in chemoresistant cancer cell lines. DCN is a small leucine-rich proteoglycan that exists and functions in stromal and epithelial cells. Accumulating evidence suggests that DCN affects the biology of several types of cancer by directly/indirectly targeting the signaling molecules involved in cell growth, survival, metastasis, and angiogenesis, however, the molecular mechanisms of DCN in chemoresistance and its clinical relevance are still unknown. Here we assumed that DCN silencing cells increase chemosusceptibility to S-1, consisted of tegafur, prodrug of 5-fluorouracil. We first established DCN knockdown transfectants derived from oral cancer cells for following experiments including chemosusceptibility assay to S-1. In addition to the in vitro data, DCN knockdown zenografting tumors in nude mice demonstrate decreasing cell proliferation and increasing apoptosis with dephosphorylation of AKT after S-1 chemotherapy. We also investigated whether DCN expression predicts the clinical responses of neoadjuvant chemotherapy (NAC) using S-1 (S-1 NAC) for oral cancer patients. Immunohistochemistry data in the preoperative biopsy samples was analyzed to determine the cut-off point for status of DCN expression by receiver operating curve analysis. Interestingly, low DCN expression was observed in five (83%) of six cases with complete responses to S-1 NAC, and in one (10%) case of 10 cases with stable/progressive disease, indicating that S-1 chemosensitivity is dramatically effective in oral cancer patients with low DCN expression compared with high DCN expression. Our findings suggest that DCN is a key regulator for chemoresistant mechanisms, and is a predictive immunomarker of the response to S-1 NAC and patient prognosis.

Topics: Aged; Aged, 80 and over; Animals; Antineoplastic Agents; Biomarkers, Tumor; Biopsy; Cell Line, Tumor; Decorin; Drug Combinations; Female; Gene Knockdown Techniques; Humans; Immunoblotting; Immunohistochemistry; Male; Mice, Nude; Middle Aged; Mouth Neoplasms; Neoadjuvant Therapy; Neoplasms, Squamous Cell; Oxonic Acid; Tegafur; Xenograft Model Antitumor Assays

An 82-year-old man died because of squamous cell carcinoma of the right lung with metastasis to the left femoral bone. At the age of 75 years, he was admitted to our hospital because of hematemesis. Widespread type 3 gastric cancer was detected in the lesser curvature. Computed tomography(CT)showed multiple liver metastases. Preoperative chemotherapy with TS-1/cisplatin(CDDP)was administered. TS-1 was orally administered at 80mg/body/day and CDDP was administered by intravenous infusion at 20mg/body/day every week for 3 weeks and this was followed by a drug-free 2-week period as the first course. After the fourth course, gastrectomy was performed for the primary lesion and radiofrequency ablation(RFA)was performed for the liver metastases. The patient survived for more than 7 years with a complete response (CR)and died thereafter because of squamous cell carcinoma of the lung.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Autopsy; Cisplatin; Drug Combinations; Humans; Liver Neoplasms; Male; Neoplasms, Squamous Cell; Oxonic Acid; Stomach Neoplasms; Tegafur; Time Factors; Treatment Outcome

Induction chemotherapy (ICT) has been used to select patients for organ preservation and determine subsequent treatments in patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN). Still, the clinical outcomes of LASCCHN patients who showed response to ICT are heterogeneous. We evaluated the efficacy of interim 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) after ICT in this specific subgroup of LASCCHN patients who achieved partial response (PR) after ICT to predict clinical outcomes after concurrent chemoradiotherapy (CCRT).. Twenty-one patients with LASCCHN who showed PR to ICT by Response Evaluation Criteria In Solid Tumors before definitive CCRT were chosen in this retrospective analysis. FDG-PET was performed before and 2-4 weeks after ICT to assess the extent of disease at baseline and the metabolic response to ICT, respectively. We examined the correlation of the metabolic response by the percentage decrease of maximum standardized uptake value (SUVmax) on the primary tumor or lymph node after ICT or a specific threshold of SUVmax on interim FDG-PET with clinical outcomes including complete response (CR) rate to CCRT, progression-free survival (PFS), and overall survival (OS).. A SUVmax of 4.8 on interim FDG-PET could predict clinical CR after CCRT (100% vs. 20%, p=0.001), PFS (median, not reached vs. 8.5 mo, p<0.001), and OS (median, not reached vs. 12.0 months, p=0.001) with a median follow-up of 20.3 months in surviving patients. A 65% decrease in SUVmax after ICT from baseline also could predict clinical CR after CCRT (100% vs. 33.3%, p=0.003), PFS (median, not reached vs. 8.9 months, p<0.001) and OS (median, not reached vs. 24.4 months, p=0.001) of the patients.. These data suggest that interim FDG-PET after ICT might be a useful determinant to predict clinical outcomes in patients with LASCCHN receiving sequential ICT followed by CCRT.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Fluorodeoxyglucose F18; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasms, Squamous Cell; Oxonic Acid; Positron-Emission Tomography; Radiopharmaceuticals; Radiotherapy Dosage; Radiotherapy, Conformal; Remission Induction; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Tegafur; Treatment Outcome