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)

A 46-year-old Japanese female with advanced gastric cancer with positive peritoneal cytology and who was refractory to methotrexate plus 5-FU sequential chemotherapy received low-dose, fractional irinotecan hydrochloride (CPT-11) in combination with cisplatin. This regimen could be repeated biweekly on an outpatient basis and was well tolerated. After 8 cycles of administration, a negative change in peritoneal cytology subsequently enabled a total gastrectomy, splenectomy, and cholecystectomy with a D3 lymph node dissection. The rationale for a low-dose, fractional administration of CPT-11 in combination with cisplatin is the synergistic antitumor activity obtained through the ability of SN-38 to potentiate cisplatin-induced cytotoxicity, as well as the increased therapeutic efficacy of a protracted CPT-11 administration over more intense treatment schedules. As far as we are aware, this case report demonstrates for the first time that a low-dose, fractional administration of CPT-11 with cisplatin can successfully produce a negative change in peritoneal lavage cytology, and potentiates a R0 resection in a 5-FU resistant advanced gastric cancer patient. This suggests that this combination could be an effective regimen for potentially disseminated, 5-FU resistant patients.
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PMID:[Successful downstaging by a low-dose, fractional administration of irinotecan hydrochloride (CPT-11) in combination with cisplatin in peritoneal lavage cytology positive, 5-fluorouracil refractory advanced gastric cancer patients]. 1522 15

We developed concise, accurate prediction models of the in vitro activity for 8 anticancer drugs (5-FU, CDDP, MMC, DOX, CPT-11, SN-38, TXL and TXT), along with individual clinical responses to 5-FU using expression data of 12 genes. We first performed cDNA microarray analysis and MTT assay of 19 human cancer cell lines to sort out genes which were correlative in expression levels with cytotoxicities of the 8 drugs; we selected 13 genes with proven functional significance to drug sensitivity from a huge number of potent prediction marker genes. The correlation significance of each was confirmed using expression data quantified by real-time RT-PCR, and finally 12 genes (ABCB1, ABCG2, CYP2C8, CYP3A4, DPYD, GSTP1, MGMT, NQO1, POR, TOP2A, TUBB and TYMS) were selected as more reliable predictors of drug response. Using multiple regression analysis, we fixed 8 prediction formulae which embraced the variable expressions of the 12 genes and arranged them in order, to predict the efficacy of the drugs by referring to the value of Akaike's information criterion for each sample. These formulae appeared to accurately predict the in vitro efficacy of the drugs. For the first clinical application model, we fixed prediction formulae for individual clinical response to 5-FU in the same way using 41 clinical samples obtained from 30 gastric cancer patients and found to be of predictive value in terms of survival, time to treatment failure and tumor growth. None of the 12 selected genes alone could predict such clinical responses.
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PMID:Concise prediction models of anticancer efficacy of 8 drugs using expression data from 12 selected genes. 1523 42

Sixteen patients with highly-advanced gastric cancer were administered low-dose TS-1 and CDDP as a first-line treatment, followed by either paclitaxel or CPT-11/CDDP as a second-line treatment. The results of the 2 second-line treatments are reported herein. Overall response rate for the first-line treatment was 55.6%. For the second-line treatments, responses were noted in both the paclitaxel group and the CPT-11/CDDP group. Overall MST was 16.3 months and 1-year survival was 60%. The paclitaxel group, however, showed significantly better prognoses than the CPT-11/CDDP group. Adverse reactions to the first-line treatment were grade 3 leukopenia in 1 patient, with no other reactions over grade 2 observed. No adverse reaction greater than grade 2 was noted during administration of the second-line treatments. These results appear to present ample data that a first-line treatment of low-dose TS-1/CDDP followed by a second-line treatment of paclitaxel at 1/week in the outpatient setting yields improved prognoses and minimal adverse reactions.
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PMID:[Examination of second-line therapies following administration of low-dose TS-1+CDDP for highly-advanced gastric cancer]. 1527 83

A 71-year-old man underwent distal partial gastrectomy for gastric cancer. Four years after surgery, the tumor marker was elevated. Examinations by computed tomography (CT) revealed para-aortic lymphnode swelling and hydronephrosis. The patient treated oral administration of TS-1 (120 mg/day). After 3 courses of treatment of TS-1, progressive disease was observed. TS-1+CPT-11 (TS-1 120 mg/day day 1-14, CPT-11 100 mg/day day 1, 15) combination therapy was then chosen as second-line chemotherapy. After 5 courses of combination therapy, the tumor marker was decreased and para-aortic lymphnodes could not be detected by CT. Only grade 2 leukopenia was observed as an adverse event during the therapy. TS-1+CPT-11 combination therapy could be useful as the second-line chemotherapy for cases of TS-1 resistant recurrent gastric cancer.
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PMID:[A case of TS-1 resistant recurrent gastric cancer responding to TS-1 +CPT-11 combination therapy]. 1527 91

The predictive values of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) gene expressions were retrospectively evaluated in patients with gastric cancer treated by a regimen containing S-1. The study population consisted of 53 patients registered into different two phase II studies for metastatic gastric cancer; 27 patients treated by S-1-alone study: 26 patients treated with S-1 combined with irinotecan (CPT-11). TS and DPD gene expressions in primary tumours were measured by the real-time reverse transcription PCR method. There was no statistical difference in DPD gene expression in terms of response in cases treated with S-1 alone and those treated with S-1 plus CPT-11. TS mRNA of responding tumours was lower than that of nonresponding ones when treated with S-1 (P<0.005). In the S-1-alone group, taking TS cutoff as the median values, the response rate in the low TS group was 50%, but only 8% in the high TS group (P<0.05). Patients with low TS gene expression survived longer than those with high TS gene expression (P<0.0001). However, there was no statistically significant difference in response rate and survival between patients with low TS tumours and those with high TS tumours, when the cutoff was taken as the median value of TS gene expression in the group treated with S-1 plus CPT-11. In conclusion, treatment effects of S-1 monotherapy for gastric cancer were determined by the status of TS gene expression, regardless of DPD gene expression. TS predictive power was overcome by CPT-11 combination therapy with S-1.
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PMID:Thymidylate synthase predictive power is overcome by irinotecan combination therapy with S-1 for gastric cancer. 1535 15

We have experienced a case of gastric cancer with multiple liver metastases resistant to combined treatment of TS-1 and CDDP. After the treatment with TS-1 and CDDP, abdominal CT demonstrated a progressive growth of metastatic liver tumor. Administration of CPT-11 (80 mg/body) by a hepatic arterial infusion inhibited the growth of metastatic liver tumor and decreased serum levels of CEA and CA19-9 for several months without a significant adverse side effect.
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PMID:[CPT-11 hepatic arterial infusion chemotherapy for metastatic liver tumor from gastric cancer]. 1555 27

Recently, new promising anti-tumor agents such as TS-1, taxanes, and CPT-11 have been approved for gastric cancer treatment. These agents showed a better response and may contribute to a patient's survival and quality of life. However, there are cases with advanced and recurrent gastric cancer that are resistive or tolerant to these agents. We report two cases in which the patients had suffered symptomatic local recurrence during the chemotherapy. Consequently, they had been treated with radiotherapy in order to improve their clinical status. We also discuss the significance of radiotherapy in gastric cancer.
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PMID:[Two cases of advanced and recurrent gastric cancer treated with the combination of chemotherapy and radiation]. 1555 45

LV (l-LV)/5-FU therapy has been used broadly and is considered to be a standard treatment for large bowel cancer due to an enhancing therapeutic effect of 5-FU. According to recent clinical study reports on large bowel cancer in Europe and the United States, various administration methods of LV/5-FU with a combination of other drugs have been devised. It appeared that 5-FU used together in bolus and continuous infusions have yielded outstanding results. Although the basis of combination therapy for gastric cancer seemed to be LV/5-FU, there were many reports on TS-1 combined with other drugs because the oral medicine TS-1 was domestically available for the past one or two years. Currently, controlled randomized trials of LV/5-FU therapy and TS-1 have been ongoing. However, when patients cannot take oral intakes, LV/5-FU therapy is important. It seems that LV/5-FU therapy in combination with other drugs, in particular, CDDP, CPT-11, paclitaxel, docetaxel, oxaliplatin, and ETP will be given as candidates for the standard treatment of gastric cancer.
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PMID:[Combination chemotherapy for gastric cancer including LV/5-FU]. 1557 Sep 19

There is no chemotherapy considered to be standard treatment for advanced gastric cancer worldwide, and there is no consensus as to whether combination or single agent therapy is preferred. In the phase I portion, a dose-escalation study of cisplatin (CDDP) combined with TS-1, new oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). TS-1 was given orally at 40 mg/m2 bid for 21 consecutive days following a 2-week rest. CDDP was planned to be given intravenously on day 8, at a dose of 60, 70, or 80 mg/m2, depending on the DLT. Treatment was repeated every 5 weeks, unless disease progression was observed. In the phase I portion, the MTD of CDDP was presumed to be 70 mg/m2, because 33.3% of patients (2/6) developed DLTs; mainly neutropenia. Therefore, the RD of CDDP was estimated as 60 mg/m2. In the phase II portion, 19 patients including 6 patients of the RD phase I portion were evaluated. The median administered courses was 4 (range: 1-8). The incidence of haematological and non-haematological toxicities (> or = grade 3) was 15.8 and 26.3%, respectively, but all were manageable. The RR was 74% (14/19, 95%) confidence interval: 54.9 (90.6%), and the median survival days were 383. This regimen is considered to be active against AGC with acceptable toxicity. In addition, currently, a randomized phase III study (JCOG 9912) for AGC patients not treated previously with chemotherapy is underway in Japan. It compares three arms: 5-FU alone, TS-1 alone and CPT-11 with CDDP therapy. We also initiated a randomized phase III study comparing TS-1 alone, and with CDDP for AGC. From those two phase III studies, we may be able to evaluate the clinical benefit of TS-1 in combination with CDDP versus TS-1 single, or 5-FU combined with CDDP therapy in terms of survival benefits and improving the QOL for AGC patients.
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PMID:[Combination chemotherapy of TS-1 +cisplatin for inoperable gastric cancer]. 1557 Sep 20

The effectiveness of chemotherapy for metastatic gastric cancer has been already revealed. But a standard chemotherapy has not been established yet. New agents such as TS-1, CPT-11 and taxanes are improving the response rates and also the survivals for gastric cancer. Including these new drugs, several randomized phase III trials are ongoing in Japan. In the near future, the candidate for standard resume will be sent abroad. In this article, we described the current state of CPT-11 combined chemotherapy for gastric cancer. Among various CPT-11- combined chemotherapy, CPT-11 + TS-1 is the most effective and less toxic treatment.
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PMID:[CPT-11 combined chemotherapy for metastatic gastric cancer]. 1557 Sep 23


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