s-1-(combination) and Edema

Oral fluoropyrimidines are used for the first-line treatment of metastatic breast cancer to avoid severe adverse effects, although firm supporting evidence is lacking. We aimed to establish whether S-1 is non-inferior to taxanes in this setting.. We did an open-label, non-inferiority, phase 3 trial at 154 hospitals in Japan. We enrolled individuals who had HER2-negative metastatic breast cancer who had received no chemotherapy for advanced disease, and who were resistant to endocrine treatment. Patients were randomly assigned (1:1) either to taxane (docetaxel 60-75 mg/m(2) at intervals of 3-4 weeks; paclitaxel 80-100 mg/m(2) weekly for 3 of 4 weeks; or paclitaxel 175 mg/m(2) at intervals of 3-4 weeks) or to S-1 (40-60 mg twice daily for 28 consecutive days, followed by a 14-day break). Randomisation was done centrally with the minimisation method, with stratification by institution, liver metastasis, oestrogen and progesterone receptor status, previous treatment with taxanes or oral fluorouracil, and time from surgery to recurrence. The primary endpoint was overall survival, with a prespecified non-inferiority margin of 1·333 for the hazard ratio (HR). The primary efficacy analysis was done in the full analysis set, which consisted of all patients who took at least one study treatment and who had all data after randomisation. This trial is registered with the University Hospital Medical Information Network, Japan (protocol ID C000000416).. Between Oct 27, 2006, and July 30, 2010, we enrolled 618 patients (309 assigned to taxane; 309 assigned to S-1). The full analysis set consisted of 286 patients in the taxane group and 306 in the S-1 group. Median follow-up was 34·6 months (IQR 17·9-44·4). Median overall survival was 35·0 months (95% CI 31·1-39·0) in the S-1 group and 37·2 months (33·0-40·1) in the taxane group (HR 1·05 [95% CI 0·86-1·27]; pnon-inferiority=0·015). The most common grade 3 or worse adverse events were neutropenia (20 [7%] of 307 patients in the S-1 group vs nine [3%] of 290 patients in the taxane group), fatigue (ten [3%] vs 12 [4%]), and oedema (one [<1%] vs 12 [4%]). Treatment-related deaths were reported in two patients in the taxane group.. S-1 is non-inferior to taxane with respect to overall survival as a first-line treatment for metastatic breast cancer. S-1 should be considered a new option for first-line chemotherapy for patients with HER2-negative metastatic breast cancer.. Comprehensive Support Project for Oncology Research of the Public Health Research Foundation, Japan; Taiho.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Disease Progression; Disease-Free Survival; Docetaxel; Drug Combinations; Edema; Fatigue; Female; Follow-Up Studies; Health Status; Humans; Liver Neoplasms; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Survival Rate; Taxoids; Tegafur

Pancreatic cancer is frequently complicated by malignancies in other organs. However, synchronous triple cancers including pancreatic cancer have been seldom reported in the English language literature.. We describe the rare case of a 77-year-old man with triple cancers of the pancreas, stomach, and cecum. Biopsies revealed that all three tumors were adenocarcinomas. The pancreatic and gastric tumors were positive for cytokeratin 7 and negative for cytokeratin 20, whereas the cecal tumor was negative for cytokeratin 7 and positive for cytokeratin 20. K-ras mutations were present at codon 12 in the pancreatic tumor and at codon 13 in the cecal tumor, but were absent from the gastric tumor. Since the three tumors had different characteristics, the patient was diagnosed with synchronous triple cancers. Because invasive surgery was required to remove all three tumors and the patient had risk factors for surgery, we elected to treat him with chemotherapy. All three cancers were markedly reduced in size by treatment with cycles of 100 mg/day S-1 for 2 weeks, followed by a 1-week rest. The patient later developed hypoproteinemia and anasarca, which was diagnosed as pancreatic exocrine insufficiency due to pancreatic head cancer. Treatment with pancrelipase resulted in dramatic improvements in hypoproteinemia and anasarca.. This is the first case report in which S-1 was effective in triple cancers of the pancreas, stomach, and cecum. Patients with pancreatic head cancer should be monitored for pancreatic exocrine insufficiency.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Cecal Neoplasms; Drug Combinations; Edema; Humans; Hypoproteinemia; Keratin-20; Keratin-7; Male; Mutation; Neoplasms, Multiple Primary; Oxonic Acid; Pancreatic Neoplasms; Pancrelipase; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins; Stomach Neoplasms; Tegafur; Treatment Outcome

Chemotherapy with TS-1 has recently become the first-line chemotherapy for recurrent and unresectable gastric cancer in Japan. Therefore, the establishment of a second-line chemotherapy is needed for cases that show resistance and aberrant effect to TS-1. In this study, 7 patients were treated with weekly administrations of paclitaxel after TS-1 treatment. We assessed the therapeutic effect and feasibility of chemotherapy with weekly administration of paclitaxel. Our results showed that weekly administration of paclitaxel could be a promising regimen as a second-line chemotherapy after TS-1.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Edema; Feasibility Studies; Female; Humans; Infusions, Intravenous; Leukopenia; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Pyridines; Stomach Neoplasms; Tegafur

S-1, an antineoplastic formulation of a fluorinated pyrimidine derivative containing tegafur (FT), CDHP, and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1, was recently developed by Taiho Pharmaceutical Co., Ltd., with the aim of prolonging the effective plasma concentration of 5-fluorouracil (5-FU) over that produced by FT alone and reducing its dose-limiting gastrointestinal toxicity. As a part of the S-1 toxicity study, a 13-week oral repeated dose toxicity study and a recovery study using male and female rats was conducted. Doses of S-1 were adjusted to deliver 1.5, 5, and 15 mg/kg/day as doses of FT, and FT was given at 15 mg/kg/day. The following results were obtained. 1. In clinical observation, edema of the limbs and face or swelling of the auricle of the ear and an anemic appearance were observed in both sexes in the 15 mg/kg/day group as dose of FT. Subsequently, males in this group developed severe anemia, decreased spontaneous motor activity, emaciation, and subnormal skin temperature, and many males died. In the survivors, keratosis of the palm, sole, or tail was observed, with necrosis and loss of the tail tip in the severe cases. 2. Body weight gain was suppressed from about week 2 of treatment in both sexes in the 15 mg/kg/day group as dose of FT, and there was almost no weight gain after week 4-5. Food consumption was consistently less than the control value for males in the 15 mg/kg/day group as dose of FT throughout the treatment period. 3. No marked changes were observed in water intake and on opthalmologic examination. 4. In the fecal test for occult blood, a positive tendency was observed in both sexes in the 15 mg/kg/day group as dose of FT. 5. Urinalysis disclosed a slight increase in protein and decrease in sodium, potassium, and chloride in males, and an increase in protein in females in the 15 mg/kg/day group as dose of FT. 6. Hematologically, both sexes in the 15 mg/kg/day group as dose of FT showed decreases in red blood cell count, hemoglobin, and hematocrit, and increases in platelet count and fibrinogen, with a slight decrease in white blood cell count in males. 7. In the blood biochemical test, abnormal findings included increases in total cholesterol and free cholesterol, and decreases in non-esterified fatty acid and albumin in both sexes in the 15 mg/kg/day group as dose of FT. 8. In organ weight measurement, abnormal changes included a decrease in thymus weight in both sexes in the 5 mg/kg/day or higher dosage gr

Topics: Administration, Oral; Animals; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Blood Chemical Analysis; Body Weight; Bone Marrow; Drug Combinations; Edema; Female; Hematologic Tests; Lymph Nodes; Male; No-Observed-Adverse-Effect Level; Organ Size; Oxonic Acid; Pyridines; Rats; Tegafur; Thymus Gland; Urine