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

A 58-year-old man was diagnosed as having type 3 gastric cancer (poorly differentiated adenocarcinoma). He underwent total gastrectomy with splenectomy, as well as D3 dissection, and received postoperative chemotherapy combining oral uracil and futrafur (UFT) with cisplatin (CDDP), but results showed recurrence of multiple abdominal lymph node metastases around the aorta. He therefore received various anticancer drug regimens (irinotecan [CPT-11]/CDDP; 1 M tegafur-0.4 M gimeracil-1 M oteracil potassium [TS-1], methotrexate (MTX)/5-fluorouracil); however, final results showed growth of lymph node metastasis and simultaneous worsening of his general condition. The patient then received combined administration of doxifluridine (5'-DFUR)/docetaxel (5'-DFUR, 1000 mg/body [666.7 mg/m(2)], given by consecutive daily administration, orally, for days 1-14; and docetaxel, 80 mg/body [60 mg/m(2)], on day 8, by venous drip, every 3 weeks). Three courses of this regimen resulted in approximately 90% reduction of the abdominal lymph node size, disappearance of the right cervical lymph node metastasis, reductions of the levels of two tumor markers (carcinoembryonic antigen [CEA] and carbohydrate antigen [CA]19-9), and improvement of his general condition. In total, seven courses of the regimen were carried out. The patient died on day 298 after starting this combined regimen and showed a response period of 126 days. The primary toxicity identified was neutropenia (grade 4), as well as other low-grade (grade 1, 2) hematological and nonhematological toxicities. In the field of gastric cancer treatment, especially for patients showing multiple resistance to anticancer drugs, an effective therapy is critically needed.
Gastric Cancer 2002
PMID:Effectiveness of doxifluridine (5'-DFUR)/docetaxel against advanced/recurrent gastric cancer showing resistance to various anticancer drug regimens. 1249 Oct 82

We retrospectively evaluated the efficacy of chemotherapy regarding symptom control, toxicity and discharge rate in 39 patients with gastric or colorectal cancer. Treatment consisted of TS-1 (n = 16), TS-1 + CPT-11 (n = 8), CDDP + CPT-11 (n = 5), paclitaxel (n = 8) and MTX + 5-FU (n = 4) for gastric cancer and 5-FU + l-leucovirin (n = 6), 5-FU + CPT-11 (n = 5), MMC + CPT-11 (n = 8) and 5-FU protracted continuous infusion (n = 5) for colorectal cancer. The rates of symptom improvement were the following: pain 60% (10/15), general fatigue 56% (5/9) and abdominal fullness 53% (8/15). 87% (34/39) of the patients were discharged from hospital and continued chemotherapy as outpatients grade 3 toxicities were the following: anemia 10.3%, nausea and/or vomiting 7.7%, diarrhea 5.1%. There was no treatment related death. The rates of outpatient based treatment duration improvement were the following: gastric cancer: 47.6%, colorectal cancer: 72%. These data suggest that these treatments for gastric and colorectal cancer are safe and improve the patients' QOL.
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PMID:[Effectiveness of chemotherapy for outpatients with gastric or colorectal cancer]. 1253 32

The current basic and clinical studies of S-1 (TS-1) were reviewed. S-1 is a novel oral dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine (DIF) based on a biochemical modulation of 5-fluorouracil (5-FU); S-1 contains tegafur (FF) and two types of enzyme inhibitor, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1. In pharmacokinetic studies, S-1 showed high 5-FU concentration in blood for long periods of time. In a combined analysis of two pivotal late phase II studies in gastric cancer, the overall response rate was 44.6% (45/101), and median survival time and 1-year survival rate were 244 days and 37%, respectively. A postmarketing survey was conducted, and in the interim analysis, tolerability and safety profiles were shown in 3294 patients with gastric cancer. The oral dose form and low incidence of adverse reactions permit treatment on an outpatient basis. To evaluate the survival benefit of S-1 in advanced gastric cancer, a phase III study of S-1 vs 5-FU vs cisplatin (CDDP) plus irinotecan (CPT-11) has been conducted. The effect of S-1 in adjuvant chemotherapy is also promising. Currently, a phase III study of surgery alone vs S-1 in patients with curative resection of gastric cancer is in progress. Further therapeutic benefits are expected to be gained by combining S-1 with other chemotherapeutic agents. Several preliminary results of combination phase I/II studies of S-1 with CDDP or CPT-11 have recently been obtained, and phase II studies are in progress. Thus, S-1 is currently the first candidate as the standard anticancer drug for gastric cancer. Further evaluations by well-controlled clinical trials are still needed.
Gastric Cancer 2003
PMID:S-1 in gastric cancer: a comprehensive review. 1277 12

We report a patient with peritoneal metastasis from gastric cancer who responded to weekly chemotherapy with paclitaxel (TXL) as the third line treatment and could take meals for half a year. The patient was a 64-year-old man who underwent total gastrectomy for advanced gastric cancer with peritoneal metastasis. He was first treated with TS-1 as an outpatient treatment; however, tumor markers rose. He could not take meals and had to be hospitalized. CPT-11 was infused on the second line, but due to disease progress, the patient was administered weekly TXL. TXL (70 mg/m2) was infused over 1 hour after short premedication. Administration was continued for 3 weeks followed by 1 week rest. The tumor markers decreased, and he could take meals and was discharged from hospital. The toxic events were leukopenia (grade 2), alopecia (grade 2) and pneumonia (grade 3).
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PMID:[A patient with peritoneal metastasis from gastric cancer who responded to weekly chemotherapy with paclitaxel on the third line and could take meal]. 1293 74

There is no standard chemotherapy for advanced gastric cancer. A combination of CPT-11 and cisplatin was evaluated for response and toxicity in Asians. 38 patients with histologically proven stage IV gastric/gastroesophageal junction adenocarcinoma were treated with CPT-11 50 mg/m2 and cisplatin 30 mg/m2 weekly for 3 weeks. Each cycle was repeated every 28 days. The median number of cycles was 1.66 (range 0.33-4.33). Dose delay was needed in 11 (29%) patients and dose reductions in 19 (50%) patients. The overall response rate was 42%. There was no complete response. Grade 3 and 4 hematological toxicity was 26%. Grade 3 or 4 diarrhea was not common. Median time to progression for all patients was 15 weeks. Median duration of survival of all patients was 42 weeks. Patients with better performance status and no prior chemotherapy did better. CPT-11 and cisplatin is a useful regimen with significant but manageable toxicity that can be administered without a central venous catheter.
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PMID:CPT-11 and cisplatin in the treatment of advanced gastric cancer in Asians. 1296 70

The limited effectiveness of chemotherapy in esophageal cancer used to palliate metastatic disease or to combine with radiotherapy in locally advanced disease has prompted the evaluation of new systemic agents. Irinotecan (CPT-11, Camptosar) has shown promising activity in a number of gastrointestinal cancers, including esophageal cancer. The phase II evaluation of the combination of weekly irinotecan and cisplatin has shown encouraging response rates exceeding 30% to 50% in esophageal and gastric cancer. Novel regimens include the combination of irinotecan with mitomycin (Mutamycin), the taxanes docetaxel (Taxotere) and paclitaxel, and continuous infusion fluorouracil (5-FU). Irinotecan is an active radiosensitizer, and trials have evaluated the combination of irinotecan with concurrent radiotherapy. We completed a phase I trial combining weekly irinotecan, cisplatin, and concurrent radiotherapy in locally advanced esophageal cancer. Minimal toxicity has been observed, with no grade 3/4 esophagitis or diarrhea, and hematologic toxicity was also surprisingly minimal. Full doses of weekly irinotecan (65 mg/m2) and cisplatin (30 mg/m2) could be combined safely with concurrent radiotherapy, with a significant rate of pathologic complete response. Phase II evaluation of this chemoradiotherapy regimen as preoperative therapy is planned at single institutions and at the cooperative group level in the United States. Further phase I and II investigation of combined irinotecan, cisplatin, and concurrent radiation is ongoing with the addition of targeted agents, including celecoxib (Celebrex), cetuximab (Erbitux), and bevacizumab (Avastin). Alternative combinations of irinotecan with radiotherapy, including the addition of docetaxel and continuous infusion 5-FU, are also undergoing phase I and II evaluation.
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PMID:Irinotecan in esophageal cancer. 1456 46

5-FU has been a key chemotherapeutic agent in the treatment of advanced or recurrent gastric cancer. In order to enhance the effect of 5-FU, biochemical modulation or combined chemotherapy has been developed. Although several phase III studies have been reported in 1990's, a standard chemotherapeutic regimen has not been established worldwide. Recently, newly developed anticancer agents such as CPT-11, TS-1, Paclitaxel, or Docetaxel can be clinically used for advanced gastric cancer either single agent or in combination that may further improve the quality of life and prolong the survival of patients with gastric cancer. In Japan, postoperative adjuvant chemotherapy has been actively developed to enhance survival benefit of surgery for patients with gastric cancer. There were a few positive single randomized controlled study showing benefit of adjuvant chemotherapy with a high evidence level. However, all reports of meta-analysis of adjuvant chemotherapy for gastric cancer indicated the survival benefit of adjuvant chemotherapy. At present, a nation-wide randomized controlled study in the postoperative adjuvant setting for gastric cancer using TS-1 (ACTS-GC) is under way that may clarify the effect of postoperative adjuvant chemotherapy in gastric cancer.
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PMID:[Chemotherapy for gastric cancer]. 1465 Sep 54

A 57-year-old male patient with upper epigastric discomfort was introduced to our hospital from another clinic because of gastric cancer. Several examinations showed massive liver metastasis and paraaortic lymph node metastasis from Type-3 gastric cancer beneath the posterior wall of the pyloric antrum. First we tried infusion of CDDP (10 mg/day for days 1-5 and 8-12) and continuous infusion of 5-FU (500 mg/day for 14 days). Concurrently, we added infusion of CPT-11 (80 mg/day on days 1,8). After 3 courses of chemotherapy, the tumor had decreased remarkably in size. Moreover, liver metastasis and paraaortic lymph node metastasis had vanished. This regimen thus appears to be effective for advanced gastric carcinoma.
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PMID:[A case of advanced cancer with liver metastasis and paraaortic lymph node metastasis responding remarkably to combination chemotherapy of low-dose CDDP, 5-FU and CPT-11]. 1465 Sep 68

Potential benefits of neoadjuvant therapy for locally advanced gastric cancer include tumor downstaging and an increased R0 resection rate. Potential disadvantages include increased surgical complications. This study assesses postoperative morbidity and mortality by comparing patients undergoing gastrectomy with and without neoadjuvant chemotherapy. From October 1998 to July 2002, a total of 34 patients with locally advanced gastric cancer were placed on a phase II neoadjuvant chemotherapy protocol consisting of two cycles of CPT-11 (75 mg/m(2)) with cisplatin (25 mg/m(2)). Demographic, clinical, morbidity, and mortality data were compared for these patients (CHEMO) versus 85 patients undergoing gastrectomy without neoadjuvant chemotherapy (SURG). The CHEMO patients were more likely to be less than 70 years of age (P< or =0.01), have proximal tumors (P< or =0.01), and undergo proximal gastrectomy (P< or =0.025). Fifty-two percent of SURG patients had T3/T4 tumors compared to 19% of CHEMO patients, consistent with tumor downstaging. The R0 resection rate was similar (80%). Morbidity was 41% in CHEMO patients and 39% in SURG patients. There were five postoperative deaths (4.4%), two in the CHEMO group and three in the SURG group (P=NS). It was concluded that neoadjuvant chemotherapy with CPT-11 and cisplatin is not associated with increased postoperative morbidity compared to surgery alone. CPT-11-based neoadjuvant chemotherapy should be tested further in combined-modality treatment of gastric cancer.
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PMID:Complications of gastrectomy following CPT-11-based neoadjuvant chemotherapy for gastric cancer. 1467 11

Gastric cancer is one of most common malignancies in the world. 5-fluoroyracil, CPT-11, TS-1, Paclitaxel and Docetaxel are used as chemotherapeutic agents for advanced gastric cancer, although endoscopic mucosal resection and surgical gastrectomy are potentially curative treatments. Most important problems associated chemotherapeutic agents are side effects and drug resistances. TSG101, implicated in membrane trafficking and transcriptional regulation, is upregulated in gastric cancer with multidrug resistant phenotype. Shen et al reported that transient transfection of TSG101 siRNA reduced the expression level of TSG101 protein as well as resistance to vincristine and adriamycin in gastric cancer cells. Bioinformatics, microarray analyses, SNP typing, and high-throughput functional analyses are applied for pharmacogenomics in the post-genome era. Therapeutics based on the genotyping of each patient is the future goal of personalized medicine (or tailor-made medicine) for gastric cancer.
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PMID:Pharmacogenomics on gastric cancer. 1504 60


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