s-1-(combination) and Intestinal-Neoplasms

The aim of this dose escalation study was to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs) and preliminary efficacy of docetaxel, S-1 and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer. Seventeen patients received oral S-1 (40 mg m(-2) bid) on days 1-14, intravenous cisplatin (60 mg m(-2)) and docetaxel (60, 70 or 80 mg m(-2) depending on DLT) on day 8 every 3 weeks. The MTD of this combination was presumed to be docetaxel 70 mg m(-2). At this dose level, 40% of the patients (two of five) developed grade 4 neutropenia and 20% (one of five) exhibited grade 3 nausea during the first course. Therefore, the recommended dose of docetaxel was defined as 60 mg m(-2). The DLT was neutropenia. The response rate (RR) was 88.2% (15 of 17), consisting of one complete response and 14 partial responses. There were two stable diseases but no progressive disease. Of these 15 responders, four (23.5%) with high VEGF expression showed rapid tumour regression and achieved downstaging, leading to subsequent curative gastrectomy. Three of these have been disease free for about 3 years, suggesting a complete cure. In conclusion, this regimen was tolerable and showed a quite high RR, with an appreciable downstaging rate in metastatic gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Female; Humans; Immunoenzyme Techniques; Intestinal Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur; Vascular Endothelial Growth Factor A

Both paclitaxel and S-1 are effective against gastric cancer, but the optimal regimen for combined chemotherapy with these drugs remains unclear. This phase I/II study was designed to determine the maximum tolerated dose (MTD), recommended dose (RD), dose-limiting toxicity (DLT), and objective response rate of paclitaxel in combination with S-1. S-1 was administered orally at a fixed dose of 80 mg m-2 day-1 from days 1 to 14 of a 28-day cycle. Paclitaxel was given intravenously on days 1, 8, and 15, starting with a dose of 40 mg m-2 day-1. The dose was increased in a stepwise manner to 70 mg m-2. Treatment was repeated every 4 weeks unless disease progression was confirmed. In the phase I portion, 17 patients were enrolled. The MTD of paclitaxel was estimated to be 70 mg m-2 because 40% of the patients given this dose level (two of five) had DLT. The RD was determined to be 60 mg m-2. In the phase II portion, 24 patients, including five with assessable disease who received the RD in the phase I portion, were evaluated. The median number of treatment courses was six (range: 1-17). The incidence of the worst-grade toxicity in patients given the RD was 28 and 8%, respectively. All toxic effects were manageable. The response rate was 54.1%, and the median survival time was 15.5 months. Our phase I/II trial showed that S-1 combined with paclitaxel is effective and well tolerated in patients with advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Drug Combinations; Female; Humans; Intestinal Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

Standard therapy for advanced small bowel adenocarcinoma (SBA) has not yet been established. The present study assessed the efficacy and safety of chemotherapy (CT) in association with molecular targeting approaches for SBA.. The histories of 33 advanced SBA patients from six different institutions in Japan, who received CT from 2008 to 2016, were retrospectively examined for background, clinical course and outcome.. Median patient age was 65 years (range 39-83). Primary tumor was located in the duodenum in 21 patients (67%), the ampulla of Vater in three patients (9%), the jejunum in seven patients (21%) and the ileum in one patient (3%). Histologically, well-to-moderately and poorly differentiated adenocarcinoma were identified in 20 (61%) and nine (27%) patients, respectively. Thirteen patients received a single CT regimen, seven patients received two types of CT regimen, and 13 patients received three or more CT regimens. As first-line CT, modified FOLFOX6, capecitabine plus oxaliplatin, and S-1 plus cisplatin were employed in 13, 1, and 4 patients, respectively. The response rate (RR) and median progression-free survival (PFS) were 25% and 6.0 months, respectively. Median overall survival (OS) was 13.0 months. Nine out of the 33 patients received bevacizumab-containing CT and three received cetuximab-containing CT. Median OS of bevacizumab-containing CT patients was 21.9 months. No unexpected serious adverse events were observed.. The analysis indicates that combination CT for advanced SBA is associated with modest efficacy and safety, and bevacizumab-containing CT may contribute to favorable outcome in these patients.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Capecitabine; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Intestinal Neoplasms; Intestine, Small; Japan; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxonic Acid; Retrospective Studies; Survival Rate; Tegafur

The patient was an 89-year-old male who consulted our hospital with a complaint of black stools. He had undergone gastrectomy and Roux-en Y reconstruction. Upper digestive tract endoscopy revealed a flat plate-like ulcer in the jejunum on the anal side of the gastrojejunostomy site. Biopsy findings suggested undifferentiated adenocarcinoma. Computed tomography (CT) showed cervical, mediastinal, and intraperitoneal lymph node swelling, suggesting metastasis. Extensive lymph node metastasis made curative resection impossible, and symptoms such as perforation/stenosis were absent. Therefore, surgery was not performed, and systemic hemotherapy with S-1 (80 mg/body/day) was administered. We repeated 2-week administration and 1-week discontinuation per course. After the end of the second course, upper digestive tract endoscopy revealed cicatrization of the ulcer, and CT showed a marked decrease in the lymph node size; a complete response (CR) was achieved. During the 7-month follow-up after the initial consultation (7 courses of S-1 therapy in all), there has been no exacerbation, and the quality of life (QOL) has been maintained.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Drug Combinations; Endoscopy, Gastrointestinal; Humans; Intestinal Neoplasms; Intestine, Small; Lymphatic Metastasis; Male; Oxonic Acid; Quality of Life; Tegafur; Tomography, X-Ray Computed

This is an account of a case of primary adenocarcinoma of the small intestine with peritoneal dissemination successfully treated with chemotherapy. A 64-year-old woman was admitted with a complaint of severe abdominal distension. Abdominal computerized tomography revealed a bowel obstruction with tumor and the remarkable small bowel dilation of oral side of tumor. The tumor was found at surgery to be at the ileum 15 cm proximal from the ileocecal region. Peritoneal dissemination was recognized around the ileocecal region, so ileum partial resection was performed for the primary cancer lesion and dissemination region. Pathological diagnosis of the resected specimen was adenocarcinoma with lymph nodes metastasis. The peritoneal dissemination consisted of metastatic adenocarcinoma from small intestine. After an operation, internal use of S-1 was performed as adjuvant chemotherapy. But a recurrent lesion at the ovarium was detected 6 months after surgery. The patient was subsequently treated with resection of the ovarium. For lung metastasis, the combination chemotherapy with mFOLFOX6 + bevacizumab was administered. Primary small intestinal adenocarcinoma is a rare disease, and it is often diagnosed as advanced cancer because of few characteristic symptoms. So carcinoma of the small intestine usually has a poor prognosis.

Topics: Adenocarcinoma; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Combined Modality Therapy; Drug Combinations; Female; Fluorouracil; Humans; Ileal Neoplasms; Intestinal Neoplasms; Leucovorin; Lymphatic Metastasis; Middle Aged; Organoplatinum Compounds; Ovarian Neoplasms; Oxonic Acid; Tegafur

As there is no standard treatment for advanced gastric cancer refractory to first-line chemotherapy, the feasibility of S-1 plus weekly docetaxel combined with concurrent radiotherapy was evaluated.. Ten patients were enrolled in this study. Patients were given S-1 at a daily dose of 40 mg/m(2) and docetaxel at a weekly dose of 20 mg/m(2) for 5 consecutive weeks, with concurrent radiotherapy (RT) amounting to a total irradiation dose of 45 Gy or 50.4 Gy.. Hematological toxicities were grade 3 or less except for anemia. Non-hematological toxicities were all grade 2 or less, apart from one grade 3 asthenia. There was one treatment-related death, resulting from melena, in a patient with a mechanical device in the radiation field. Planned treatment was delivered with relative dose intensity for S-1, docetaxel and RT as 94%, 98% and 97%, respectively. Median survival time of 297 days was obtained, with an objective response seen in 2 patients and symptom relief achieved in all patients.. S-1 plus weekly docetaxel combined with concurrent RT exhibited a tolerable toxicity profile with sufficient symptom palliation and prolonged survival in patients with advanced gastric cancer refractory to first-line chemotherapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Docetaxel; Drug Combinations; Drug Resistance, Neoplasm; Feasibility Studies; Female; Humans; Intestinal Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

This study was designed to examine the efficacy and compliance of S-1 for the patients with peritoneal metastasis of gastric cancer.. Sixteen consecutive patients with peritoneal metastasis of gastric cancer were treated with S-1. Their survival was compared with that of the historical control group (25 patients). Thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase and orotate phosphoribosyl transferase mRNA expression in the tumor were evaluated.. The median survival time of S-1-treated patients was 550 days, which was significantly longer than that of the historical control group (215 days). We elucidated some factors to prolong the survival of the patients treated with S-1 for peritoneal metastasis: peritoneal metastasis without other distant metastases, the combination of S-1 treatment and gastrectomy, and low expression of thymidine phosphorylase mRNA in primary tumors.. S-1 showed a surprisingly long-term survival with minimum toxicity in patients with peritoneal metastasis of gastric cancer.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Female; Gastrectomy; Humans; Intestinal Neoplasms; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Orotate Phosphoribosyltransferase; Oxonic Acid; Patient Compliance; Peritoneal Neoplasms; Stomach Neoplasms; Survival Rate; Tegafur; Thymidine Phosphorylase; Thymidylate Synthase; Time Factors; Treatment Outcome

A 72-year-old female was admitted to our hospital with the complaint of left neck lymph node swelling. Abdominal computed tomography (CT) revealed wall thickening of the small intestine and multiple lymph node metastases. Barium meal study of the small intestine showed circular stenosis. The patient was operated on under a diagnosis of tumor of the small intestine and left neck lymph node swelling. Needle biopsy of the left neck lymph node and partial resection of the small intestine was done without regional lymph node dissection because of Virchow lymph node metastasis. On the resected material a 5 x 4 cm type 2 tumor was identified. Pathological findings included poorly-differentiated adenocarcinoma, si (bladder), n 4, P 0, ly 3, v 3, H 0, M(-), Stage IV. The patient received the chemotherapy with TS-1. TS-1(80 mg/body/day) orally administered for 4 weeks followed by a drug-free 2-week period as one course. CT revealed that the metastatic lesion had shrunk markedly after the second course. A complete response (CR) was observed after one year. There were no drug side effects. At present, 3 years and 9 months after the operation, cervical and abdominal CT reveals no evidence of enlargement of the cervical and intraperitoneal lymph nodes.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Female; Humans; Intestinal Neoplasms; Intestine, Small; Lymph Nodes; Lymphatic Metastasis; Neoadjuvant Therapy; Oxonic Acid; Pyridines; Remission Induction; Tegafur