Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the first phase of this study 34 patients with advanced pancreatic cancer have been treated either with gemcitabine/cisplatin or gemcitabine/5-fluorouracil (5FU)/leucovorin combination. (Gemzar: 900 mg/m2, Cisplatin: 20 mg/m2, 5-FU: 750 mg/m2). Treatments were continued till tumor progression. There was no difference observed between the two protocols in the clinical response rates (PR=65%). On the other hand, a significant difference was found between the two protocols regarding the side effects. In the case of gemcitabine/5-FU neutropenia, thrombocytopenia and anaemia (as well as nausea and vomiting) were much less frequent compared to gemcitabine/cisplatin combination. Based on these data the efficacy of gemcitabine/5-FU combination was evaluated in 99 stage III, T1-4, N1 and stage IV, T1-4, N0-1, M1 pancreatic cancer patients throughout 364 treatment cycles. OR was achieved in 10% while stable disease in 52% of the cases. The average survival period was 8.33 months while the time to progression was 5.75 months. Based on these data we recommend gemcitabine/5-FU/leucovorin combination for the treatment of advanced pancreatic cancer.
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PMID:[Experience with the treatment of advanced pancreatic cancer in Hungary]. 1297 69

The purpose of this report is to summarize information on oxaliplatin, a drug recently approved by the U.S. Food and Drug Administration. Information provided includes regulatory history, study design, efficacy and safety results, and pertinent literature references. A single, multicenter, randomized trial, enrolling 463 patients with metastatic colorectal carcinoma whose disease had recurred or progressed during or within 6 months of completion of therapy with the combination of bolus 5-fluorouracil (FU)/leucovorin (LV) and irinotecan, was submitted. Study arms included infusional 5-FU/LV alone (arm A), oxaliplatin alone (arm B), and the combination of oxaliplatin and infusional 5-FU/LV(arm C). Oxaliplatin, at a dose of 85 mg/m2, was administered to patients in arms B and C intravenously over 2 hours in 250-500 ml of dextrose 5% in water (D5W) on day 1 only. A 200-mg/m2 dose of LV was administered simultaneously to arm C patients, in a separate bag using a Y-line, or alone to arm A patients, by i.v. infusion, over 2 hours. 5-FU was then administered to arms A and C patients, first as a bolus injection over 2-4 minutes at a dose of 400 mg/m2, then as a continuous infusion in 500 ml of D5W over 22 hours at a dose of 600 mg/m2. LV was repeated on day 2 of the cycle (arms A and C) followed by a 400-mg/m2 5-FU bolus and a 600-mg/m2 22-hour infusion. Treatment was repeated every 2 weeks. Response rate was the prespecified end point for accelerated approval. Time to progression (TTP) was a secondary end point. The prespecified primary comparison was between the 5-FU/LV regimen and the 5-FU/LV/ oxaliplatin combination regimen. The three arms were well balanced for patient prognostic factors. There were no complete responders. The partial response rates were 0%, 1%, and 9% for the 5-FU/LV, oxaliplatin, and oxaliplatin plus 5-FU/LV treatments, respectively (p = 0.0002, arm C versus arm A). The median times to radiographic tumor progression, based on available radiographs, were 2.7 months, 1.6 months, and 4.6 months, respectively (p < 0.0001, arm C versus arm A). Common adverse events associated with the combination treatment included peripheral neuropathy, fatigue, diarrhea, nausea, vomiting, stomatitis, and abdominal pain. Neutropenia was the major hematologic toxicity. Adverse events were similar in men and women and in patients <65 and > or =65 years of age, but older patients may have been more susceptible to dehydration, diarrhea, hypokalemia, and fatigue. Oxaliplatin in combination with infusional 5-FU/LV was approved for the treatment of patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed during or within 6 months of completion of first-line therapy with the combination of bolus 5-FU/LV and irinotecan. Approval was based on response rate and on an interim analysis of TTP. No results are available, at this time, that demonstrate a clinical benefit, such as improvement in disease-related symptoms or survival.
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PMID:FDA drug approval summaries: oxaliplatin. 1475 10

A 65-year-old male was admitted to our hospital because of sudden onset of upper abdominal pain due to the perforation of gastric cancer with synchronous hepatic metastasis. He underwent total gastrectomy with lymphatic dissection of D1 + alpha. Pathological diagnosis of the surgical specimen was moderately differentiated tubular adenocarcinoma. The cancer progression was fStage IV (T1, N0, H1, P0). Since 50 days after surgery, he had received oral administration of UFT (300-600 mg/day) and intermittent intrahepatic arterial infusion of 5-FU (one injection, 500 mg/2 weeks). Seven months after the start of chemotherapy, the size of hepatic lesion was reduced. Thirteen months later, the tumor became necrotic with cystic change. Furthermore, 22 months later, abdominal CT scan showed complete response. He has been well without recurrence for 38 months following the start of chemotherapy.
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PMID:[A case of gastric cancer with a synchronous hepatic metastasis responding to postoperative oral administration of UFT and intermittent intrahepatic arterial chemotherapy of 5-FU]. 1504 51

Two of the most promising new targets in the treatment of colorectal cancer are the epithelial growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF). Agents that inhibit the EGFR or bind to VEGF have demonstrated clinical activity as single agents and in combination with chemotherapy in phase II and phase III clinical trials. The most promising of these agents are cetuximab, which blocks the binding of EGF and transforming growth factor alpha (TGF-alpha) to EGFR, and bevacizumab, which binds free VEGF. Cetuximab and irinotecan have been evaluated in two clinical studies in the USA (IMCL CP02-0141 and IMCL CP02-9923). Study IMCL CP02-0141 evaluated the antitumor activity of single-agent cetuximab in patients with irinotecan-refractory, EGFR-positive metastatic colorectal carcinoma. There were 6 partial responses in 57 treated patients, for a response rate of 10.5%. Study IMCL CP02-9923 evaluated the combination of cetuximab and irinotecan in a total of 139 patients enrolled at 27 study sites. In this trial 22.5% of patients with progressive disease on irinotecan achieved an objective response (19% by investigator assessment) showing that the combination of cetuximab and irinotecan has antitumor activity in this population. A large randomized phase II trial evaluating similar study populations in Europe confirmed these findings, demonstrating response rates for cetuximab/irinotecan and cetuximab alone of 22.9% and 10.8%, respectively. The other promising agent bevacizumab is a humanized variant of the anti-VEGF monoclonal antibody. VEGF is produced by healthy and neoplastic cells. Its activities are mediated by two receptor tyrosine kinases. VEGF signaling is often a rate-limiting step in physiologic and pathologic angiogenesis. Bevacizumab has been studied as an antiangiogenic cancer therapeutic as a single agent and in combination with chemotherapy in patients with stage III and IV colon cancer. In addition to its direct antiangiogenic effects, bevacizumab may allow more efficient delivery of chemotherapy by altering tumor vasculature and decreasing the elevated interstitial pressure common in tumors. In this regard, some of the most robust phase II data using bevacizumab are from a randomized study of chemotherapy [fluorouracil (5-FU) and leucovorin (LV)] with or without bevacizumab in metastatic colorectal cancer. In this study, treatment with bevacizumab plus 5-FU/LV resulted in higher response rates, longer median time to disease progression, and longer median survival. Recently, a phase III, multicenter, double-blind, randomized, placebo-controlled trial was designed to investigate the addition of bevacizumab to first-line irinotecan, 5-FU, and LV chemotherapy (IFL). The trial showed a higher response rate, longer time to tumor progression, and prolonged overall survival in patients with metastatic colorectal cancer. It was the first large, randomized, phase III survival trial to assess the importance of targeting VEGF and tumor angiogenesis for the treatment of human cancer. Integration of novel agents targeting VEGF and EGFR with irinotecan-based chemotherapy has shown clinical activity in patients with metastatic colorectal cancer. The goal in the future will be to predict which specific chemotherapy and targeted agent combination will most likely benefit individual patients.
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PMID:Integration of novel agents in the treatment of colorectal cancer. 1530 12

This case was a 69-year-old male who had advanced gastric cancer with unresectable multiple liver metastases (Stage IV). He received a combination therapy consisting of a continuous venous infusion (cisplatin: CDDP 10 mg/body, 5-FU 500 mg/body, day 1-28). As a result, metastatic tumors in the liver completely disappeared and a total gastrectomy was sequentially performed. Four years after the surgery, neck lymph node (LN) metastases and the right adrenal metastasis appeared, and chemotherapy (TS-1, and sequentially TS-1+CDDP) was performed. But, the chemotherapy to eradicate the metastases was hardly enough to be effective. Next, docetaxel (DOC 60 mg/m2 q3w) was started. After 9 courses, they were effective and marked regressions (70%). A total of 15 courses of docetaxel administration were possible until tumor progression recurred. This regimen was not severe in toxicity for the duration except for grade 3 poor appetite. Docetaxel will be a key drug for the gastric cancer. In case of responding well to the chemotherapy, we can hope for an extended long-term survival with a continuation of this regimen.
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PMID:[A case report of the 8 year survivor--unresectable liver metastases from advanced gastric cancer (Stage IV) were completely responsive, after 4 years from a total sequential gastrectomy, combining docetaxel treatment to regress the recurrence]. 1555 83

Nedaplatin (CDGP) is designed to further improve the anti-tumor effect and to reduce adverse effects of cisplatin (CDDP), such as renal toxicity. We previously reported a combination therapy of superselective intraarterial CDGP infusion, and radiation therapy could be delivered safely with good efficacy for locoregional management of oral cancer. However, both the clinical and pathological response decreased with tumor progression. This study was performed to assess the feasibility of a new chemotherapy regimen by superselective intraarterial infusion of CDGP in patients with advanced oral carcinomas. This regimen is under way in which chemotherapy with 5-FU 500 mg/day on days 1 to 5 and superselective intra-arterial infusion of CDGP on day 6 combined with radiation therapy is being evaluated for locally advanced oral cancer. Eight patients were treated with this regimen. After evaluation of the response, patients underwent surgery as a therapeutic procedure. Both the complete and partial response rates were achieved in each 3 patients (37.5%), respectively. Histological effects classified according to Oboshi-Shimosato's criteria were grade IVa in 2 patients, grade III in 1, grade IIb in 1, grade IIa in 3, and grade I in 1. All patients were free from renal dysfunction, which is one of the adverse effects of CDDP. Moreover, most toxicity was relatively mild in all patients.
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PMID:[Clinical trial of chemotherapy by superselective intra-arterial infusion of nedaplatin combined with radiotherapy for advanced oral cancer]. 1618 22

Cyclooxygenase-2 (COX-2) inhibitors are being tried in clinics for cancer treatment. One of the mechanism by which COX-2 inhibitors suppress cancer progression is suggested to be inhibition of angiogenesis. To investigate how COX-2 inhibitors affect regulation of angiogenic factors, we studied alterations in VEGF levels in sera and plasma during COX-2 inhibitor treatment in breast cancer patients. Serum and plasma VEGF levels were monitored in 48 patients treated with the COX-2 inhibitor celecoxib together with 5-FU, epirubicine, cyclophosphamide (FEC). Serum VEGF levels showed decreases on day 3 of the first cycle (P<0.0001), followed by increases after 3 weeks (P<0.0001). Plasma VEGF levels did not show decreases on day 3 but showed increases after 3 weeks (P<0.05). The increases of VEGF levels in sera and plasma continued until the next cycle of the treatment. In patients treated with FEC alone (without celecoxib) did not show increases in serum VEGF levels during the treatment. Our data showed that treatment with COX-2 inhibitors decreased serum VEGF levels at an early time and increased VEGF levels in serum and plasma at a late time in breast cancer patients. Further studies are necessary to elucidate how COX-2 inhibitors regulate production of VEGF in different cells and different tissues in cancer patients.
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PMID:Increases in circulating VEGF levels during COX-2 inhibitor treatment in breast cancer patients. 1680 97

In the present article, we have summarized the phase I/II clinical trials on combination therapy of S-1 and docetaxel. With result of the phase I study, patients were treated with intravenous infusion of 40 mg/m2 docetaxel on day 1 and oral S-1 80 mg/m2/day on days 1 to 14 every 3 weeks. Forty eight patients received a total of 272 treatment cycles. No complete responses (CRs) and 27 partial responses (PRs) were observed for an overall response rate (CR+PR) of 56.2% (95% CI, 38-66%). Eighteen patients (37.5%) had stable disease (SD), and 3 patients (6.2%) had progressive disease (PD) as best response. The tumor control rate (CR+PR+SD) was 93.8% (95% CI, 83-98%). The median overall survival was 14.3 months (95% CI: 10.7-20.3 months) and the median time to tumor progression was 7.3 months (95% CI: 4.2-10.7 months). The most common grade 3-4 hematologic toxicities were neutropenia 58.3%, leukopenia 41.7%, febrile neutropenia 8.3%, and anemia 8.3%. The most common grade 3 nonhematologic toxicities were anorexia 14.6%, stomatitis 8.3%, nausea 6.3%, diarrhea 4.2%, constipation 4.2%, and vomiting 2.1%. No grade 4 nonhematologic toxicities were reported, and all treatment-related toxicities were resolved. The mechanisms underlying these synergistic effects of S-1 and docetaxel were examined by expression and activity analyses of 5-FU metabolic enzymes. The expressions of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) were decreased and that of orotate phosphorybosyl transferase (OPRT) was increased in mRNA, protein level and activity assay after the treatment with docetaxel and 5-FU in the TMK-1 gastric cancer cell. These findings strongly indicate that the combination chemotherapy of docetaxel and S-1 is effective against gastric carcinomas and therefore is a good candidate as a standard chemotherapeutic strategy in treating these tumors.
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PMID:[Combination chemotherapy of S-1 and docetaxel on advanced and recurrent gastric cancer]. 1689 78

While acute oxidative stress triggers cell apoptosis or necrosis, persistent oxidative stress induces genomic instability and has been implicated in tumor progression and drug resistance. In a previous report, we demonstrated that reactive oxygen species modulator 1 (Romo1) expression was up-regulated in most cancer cell lines and suggested that increased Romo1 expression might confer chronic oxidative stress to tumor cells. In this study, we show that enforced Romo1 expression induces reactive oxygen species (ROS) production in the mitochondria leading to massive cell death. However, tumor cells that adapt to oxidative stress by increasing manganese superoxide dismutase (MnSOD), Prx I, and Bcl-2 showed drug resistance to 5-FU. To elucidate the relationship between 5-FU-induced ROS production and Romo1 expression, Romo1 siRNA was used to inhibit 5-FU-triggered Romo1 induction. Romo1 siRNA treatment efficiently blocked 5-FU-induced ROS generation, demonstrating that 5-FU treatment stimulated ROS production through Romo1 induction. Based on these results we suggest that cellular adaptive response to Romo1-induced ROS is another mechanism of drug resistance to 5-FU and Romo1 expression may provide a new clinical implication in drug resistance of cancer chemotherapy.
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PMID:Drug resistance to 5-FU linked to reactive oxygen species modulator 1. 1753 4

Amyotrophic lateral sclerosis (ALS) is a degenerative disease involving both upper and lower motor neurons and the pathogenesis of this disorder is still unknown. To date, few reports have suggested that motor neuron diseases may have a paraneoplastic origin. However, it is still under discussion whether ALS occurring in cancer patients is paraneoplastic. A 60-year-old man with rectal cancer (Stage IV) having multiple lung, liver and para-aortic lymph node metastases underwent anterior resection of the rectum as palliative surgery. He was referred to our hospital for adjuvant chemotherapy. Lung and lymph node metastases decreased after 2 courses of chemotherapy using CPT-11 and 5-FU/LV but liver metastases were enlarged, following up increase in CEA. Thereafter, he suffered from muscle weakness in hands, arms, and legs and results of neurophysiologic studies were compatible with primary lateral sclerosis (ALS). For second line chemotherapy, he was treated with low-dose CDDP/5-FU over 6 courses. As a result, the size the of metastatic lesions markedly reduced and CEA was decreased to the normal level. Although significant tumor reduction was observed, his neurological symptoms rapidly progressed. He died of aspiration pneumonia 8 months after onset of the disease. Autopsy revealed that his neuropathological findings were compatible with ALS, and it was thought to be the primary cause of death in the because of absence of cancer progression. In this case the neurological syndrome was not affected by cancer therapy. Thus our case does not support the hypothesis that ALS in associated with cancer and the relationship between both disorders remains uncertain.
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PMID:Report of an autopsy case of colon cancer with amyotrophic lateral sclerosis. 1782 8


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