Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Docetaxel and paclitaxel are demonstrated to be effective for use as salvage therapy for advanced gastric cancer. Both drugs are taxane derivatives but there is only partial cross-resistance between them. For breast cancer and ovarian cancer, there have been several reports that showed docetaxel is effective for paclitaxel-resistant cancer, and vice versa. We experienced two cases of advanced gastric cancer effectively treated by sequential therapy of docetaxel and paclitaxel. One patient was a 43-year-old woman with a type 4 gastric carcinoma, and the other a 51-year-old woman who had suffered a recurrence of the gastric cancer after a total gastrectomy. At first, chemotherapy failed, so we chose docetaxel/high-dose 5-FU (HDFU) for the second-line therapy. After resistance to Docetaxel/HDFU, paclitaxel was effective for third-line treatment of both patients.
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PMID:[Two cases of advanced gastric cancer in which paclitaxel proved effective after resistance to docetaxel]. 1794 Mar 82

Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine to generate phosphatidic acid (PA) and choline. There are at least two PLD isozymes, PLD1 and PLD2. Genetic and pharmacological approaches implicate both PLD isozymes in a diverse range of cellular processes, including receptor signaling, membrane transport control, and actin cytoskeleton reorganization. Several recent studies reported that PLD has a role in signaling pathways that oppose apoptosis and promote cell survival in cancer. In this study, we examined the role of PLD in taxotere-induced apoptosis in stomach cell lines; normal stomach (NSC) and stomach cancer cells (SNU 484). Taxotere treatment resulted in increase of PLD activity. To confirm the role of PLD in taxotere-induced apoptosis, PLDs were transfected into SNU 484 cells. Overexpression of PLD isozymes resulted in inhibition of taxotere-induced apoptotic cell death, evidenced by decreased degradation of chromosomal DNA, and increased cell viability. Concurrently, Bcl-2 expression was upregulated, and taxotere-induced activation of procaspase 3 was inhibited after PLD's transfection. However, when PLD was selectively inhibited by specific siRNA-PLD1 or -PLD2, taxotere-induced apoptosis was exacerbated in SNU 484 cells. On top of this, PA -- the product of PLDs, also resulted in upregulation of Bcl-2 in SNU 484. Although PA-induced Bcl-2 expression was blocked by mepacrine, an inhibitor of phospholipase A(2) (PLA(2)), increased Bcl-2 expression by PA was not abrogated by propranolol, an inhibitor of PA phospholyhydrolase (PAP). Taken together, PLD1 and PLD2 are closely related with Bcl-2 expression together with PLA(2), but not with PAP, during taxotere-induced apoptosis in SNU 484 cells.
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PMID:Overexpression of phospholipase D suppresses taxotere-induced cell death in stomach cancer cells. 1819 Jul 95

This study evaluated the feasibility and pharmacology of intraperitoneal docetaxel (IP docetaxel) when administered weekly for 3 consecutive weeks, followed by 1 week without treatment. A total of 24 patients with peritoneal carcinomatosis of gastric cancer (10 preoperative, 7 postoperative and 7 recurrent) were enrolled in this study. Docetaxel was dissolved in an isotonic saline to a final 1 liter solution and was administered in a 1 h dosage of 25, 35, 45 and 60 mg/m(2) to determine the maximum tolerated dose (MTD). To measure the docetaxel concentration, blood and peritoneal fluid samples were collected 0.5, 1, 2, 3, 6 and 24 h after administering the drug to 15 patients. A total of 109 chemotherapy cycles were administered, with a median of four cycles per patient (range 2-9). The MTD of the weekly IP docetaxel was defined at 60 mg/m(2). At a docetaxel dosage of 60 mg/m(2) per week, the dose-limiting events of grade 3 abdominal pain and grade 3 diarrhea, which may be associated with local toxicity, occurred. Peak concentrations of peritoneal fluid ranged from 24.5 to 68.7 microg/ml. The mean ratio of the area under concentration (AUC) in the peritoneal fluid to the plasma concentration was 515. Furthermore, the mean of plasma AUC by IP docetaxel was 5.63 microg h/ml versus that of IV docetaxel at a dose of 60 mg/m(2). The response rate of the preoperative IP docetaxel was 80% (4 CR, 4 PR, 1 NC and 1 PD), which was judged with laparoscopy and peritoneal lavage cytology. Gastrectomy, with D2 lymph node dissection, was performed on all of the patients evaluated as CR. The weekly IP docetaxel demonstrated a low toxicity and high efficacy for peritoneal carcinomatosis with dual anti-cancer effects via the peritoneal surface and capillary blood supply due to its unique pharmacokinetic property.
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PMID:Dual anti-cancer effects of weekly intraperitoneal docetaxel in treatment of advanced gastric cancer patients with peritoneal carcinomatosis: a feasibility and pharmacokinetic study. 1842 92

5-Fluorouracil (5-FU) has been the most widely accepted and studied chemotherapeutic agent, and many combination chemotherapeutic regimens have been reported. However, until recently, a standard regimen for metastatic gastric cancer had not been established. The combination of S-1 and cisplatin is a good candidate as a standard first-line regimen for metastatic gastric cancer. On the other hand, interest in biochemical modulation has become wide spread recently. The low level of dihydropyrimidine denhydrogenase (DPD), thymidylate synthase (TS) activities, and a high level of orotate phosphoribosyl-transferase (OPRT) activity enhance the antitumor effect of 5-FU and S-1. Docetaxel is one of the agents that modulate these enzyme expressions and activities. Moreover, the response rate of combination therapy of docetaxel and S-1 for metastatic gastric cancer was 56.3% and median survival time was 14.3 months in a phase II study, showing it to be a good candidate for a new standard regimen for gastric cancer. A phase III collaborative study, START (S-1 and Taxotere for advanced gastric cancer randomized phase III trial), is now under way in Japan and Korea.
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PMID:Challenge for a better combination with basic evidence. 1855 30

Docetaxel is a microtubule inhibitor that has actions in the S and G(2)-M phase of the cell cycle. The pyrimidine trifluorothymidine (TFT) induces DNA damage and an arrest in the G(2)-M phase. TFT, as part of TAS-102, has been clinically evaluated as an oral chemotherapeutic agent in colon and gastric cancer. The aim of the present study was to determine the optimal administration sequence of TFT and docetaxel and to investigate the underlying mechanism of cytotoxicity. Drug interactions were examined by sulforhodamine B assays and subsequent combination index analyses, and for long-term effects the clonogenic assay was used. A preincubation with docetaxel was synergistic in sulforhodamine B (combination index 0.6-0.8) and clonogenic assays, and was accompanied by a time-dependent cell death induction (17-36%), the occurrence of polynucleation (22%), and mitotic spindle inhibition as determined by flow cytometry and immunostaining. Interestingly, administration of TFT followed by the combination displayed strong antagonistic activity, and was accompanied by less polynucleation and cell death induction than the synergistic combinations. Western blotting showed that the G(2)-M-phase arrest (25-50%) was accompanied by phosphorylation of Chk2 and dephosphorylation of cdc25c in the synergistic combinations. Together, this indicates that synergistic activity requires docetaxel to initiate mitotic failure prior to the activation of TFT damage signaling, whereas antagonism is a result of TFT cell cycle-arrested cells being less susceptible to docetaxel. Caspase 3 activation was low after docetaxel, suggestive of caspase-independent mechanisms of cell death. Taken together, our models indicate that combination treatment with docetaxel and TFT displays strong synergy when docetaxel is given first, thus providing clues for possible clinical studies.
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PMID:Synergistic interaction between trifluorothymidine and docetaxel is sequence dependent. 1895 56

Gastric cancer is a global health problem accounting for 800,000 cancer related deaths annually. Often diagnosed at an advanced stage, the treatment of gastric cancer with chemotherapy is directed towards palliating cancer related symptoms with only modest improvements in survival. In addition, no regimen has emerged as a globally accepted standard. New therapeutic options are desperately needed for the treatment of gastric cancer. Docetaxel given in combination has recently emerged as a new option for patients with advanced gastric cancer. This review focuses on the treatment of advanced gastric cancer utilizing docetaxel-based therapy and the novel additions of biotherapy to the existing cytotoxic platforms. In addition, the current investigations of docetaxel for the treatment of potentially curable gastric cancer will be discussed.
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PMID:Review of docetaxel in the treatment of gastric cancer. 1920 81

Patients with advanced gastric carcinoma have still had bad prognosis despite advances in the modern treatment era. Docetaxel, cisplatin, 5-fluorouracil (DCF) is effective, but highly toxic regimen for advanced cases. In this study, we modified the standard doses of DCF (mDCF) to evaluate the effectiveness and side effects. From July 2005 to July 2008, 37 advanced gastric cancer patients treated with at least one course of mDCF protocol as first-line treatment were included. The mDCF protocol included 60 mg/m(2) docetaxel and cisplatin for 1 day and 600 mg/m(2)/day, 5-flourouracil infusion for 5 days, repeated every 3 weeks. No patients used prophylactic granulocte -colony stimulating factor. Of the patients, 28 were male and nine were female; the median age was 53 (23-65) years. Of them, 83.8% received at least four courses of chemotherapy and 64.9% completed the preplanned six courses of treatment. Eleven (29.7%) of those patients who received mDCF in the first-line treatment used the FOLFIRI (5-FU, folinic acit, irinotekan) regimen for the second-line treatment. Response rates were evaluated according to RECIST criteria in 30 out of 37 patients. The median follow-up time was 7.1 months. The longest follow-up time was 19.9 months. Two patients (5.4%) had complete response, nine (21.6%) had partial response, and 14 (37.9%) had stabilized disease; overall, the disease was controlled in 25 patients (64.9%) whereas five patients (13.5%) had progression. Median time to progression was 6.7 months and overall survival was 10 months. The assessment of patients for grade 3-4 toxicity revealed that while 5.4% had anemia and 8.1% had neutropenia, 5.4% nausea and 5.4% diarrhea. Neutropenic fever developed in two patients, requiring hospitalization. G-CSF was used in three patients. Two patients with neutropenic fever and two with severe anemia (total number 4; 10.8%) received delayed chemotherapy. Dose reduction was required in four patients (10.8%), one due to neutropenia, one due to nephrotoxicity, and two due to nausea. No patient died due to chemotherapy toxicity. This retrospective study suggested that mDCF might have comparable efficacy with classical DFC, with better toxicity profile. However, its small size and retrospective nature should be considered when interpreting the results.
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PMID:The efficacy and safety of reduced-dose docetaxel, cisplatin, and 5-fluorouracil in the first-line treatment of advanced stage gastric adenocarcinoma. 1963 62

Despite a sharp decline in the incidence of gastric cancer during the second half of the 20th century, this malignancy remains the second leading cause of cancer mortality in the world. The incidence and mortality rate of gastric cancer increase with age; at present, the median ages at diagnosis are 67 years for men and 72 years for women in the US. This article reviews and discusses current medical treatment options for both the general population and elderly gastric cancer patients. Management of localized gastric cancer has changed significantly over recent years. Adjuvant chemoradiation is not generally recommended outside the US. After decades of trials of adjuvant chemotherapy with inconclusive results, a significant survival benefit for perioperative combination chemotherapy - as compared with surgery alone - in patients with resectable or locally advanced gastro-oesophageal cancer was recently demonstrated in the UK MAGIC trial. A further large, randomized trial from Japan demonstrated a significant survival benefit for adjuvant chemotherapy with S-1 after D2 resection for gastric cancer. However, both trials are applicable only to the population in which the trials were conducted. Specific data on elderly patients are missing. For patients with metastatic disease, oral fluoropyrimidines, such as capecitabine, have been developed. In Asian patients, treatment with the oral fluoropyrimidine S-1 is safe and effective. Docetaxel, oxaliplatin and irinotecan have demonstrated activity against gastric cancer in appropriately designed, randomized, phase III trials and have increased the available treatment options significantly. In addition, according to preliminary data, trastuzumab in combination with chemotherapy has significantly improved activity when compared to chemotherapy alone in patients with human epidermal receptor (HER)-2-positive gastric and gastro-oesophageal cancers. Thus, therapeutic decisions in patients with advanced gastric cancer may be adapted to the molecular subtype and co-morbidities of the individual patient. Data from retrospective analyses suggest that oxaliplatin seems to be better tolerated than cisplatin in elderly patients.
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PMID:Advances in the pharmacological treatment of gastro-oesophageal cancer. 1968 30

There is no standard treatment for peritoneal carcinomatosis (PC) from gastric cancer. New bidirectional chemotherapy (neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS)) was developed. The aim of the present study was to assess the safety and efficacy of NIPS and to show the selection for cytoreductive surgery on PC from gastric cancer. Seventy-nine patients with PC from gastric cancer were treated with NIPS. A peritoneal port system was introduced into the abdominal cavity. The peritoneal wash cytological examination through a port was done before and after NIPS. The patients were treated with oral TS-1 twice a daily for 21 days, followed by a 1-week rest. On day 1, 8, and 15 from the start of oral TS-1 administration, 30 mg/m(2) of Docetaxel and 30 mg/m(2) of cisplatinum with 500 ml of saline were introduced into the peritoneal cavity through the port. A median course of oral TS-1 was 2.1 course and a median time of IP chemoterapy was 5.8. Peritoneal free cancer cells (PFCCs) had been detected in 65 (82.2%) patients before NIPS, and the positive cytology changed to be negative in 41 (63.0%) patients after NIPS. After NIPS, 41 patients underwent laparotomy, and complete cytoreduction was done in 32 (78%) patients. Complete cytoreduction was done in 27 (51.9%) of 52 patients with negative cytology but in only 4 (14.8%) of 27 patients with positive cytology (P < 0.001). Patients with negative cytology after NIPS survived significantly longer than those with positive cytology. The adverse effects after NIPS were mild and there was no treatment-related deaths. The grade 3/4 hematological adverse effects were found in 2 (2.6%) patients. Grade 3 renal toxicity and port site infection was found in three patients, respectively. NIPS using a port system is a safe and effective treatment for PC. Peritoneal wash cytology through a port system is a good indicator to select the patients to perform cytoreductive surgery.
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PMID:Safety and efficacy of bidirectional chemotherapy for treatment of patients with peritoneal dissemination from gastric cancer: Selection for cytoreductive surgery. 1969 37

Recently, the significant efficacy of S-1 monotherapy or S-1 plus CDDP combination therapy has been reported. Docetaxel also has been reported to have favorable efficacy in gastric cancer. In addition, docetaxel can be administered in outpatient clinics. We investigated the efficacy and safety of S-1 plus docetaxel combination therapy for 35 naive patients with advanced gastric cancer. Docetaxel was administered at a dose of 40 mg/m(2) on day 1, and oral S-1 was administered at the full dose of 80 mg/m(2) twice daily for two weeks followed by one week rest. MST was 300 days, and the response rate was 42. 9%. Although leucopenia was observed in 31%, all patients were able to be continue this therapy. In conclusion, we considered that this S-1 plus docetaxel combination therapy was effective and safe in advanced gastric cancer, and convenient for outpatients.
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PMID:[Efficacy and safety of S-1 plus docetaxel combination therapy for patients with advanced gastric cancer]. 1983 24


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