Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0546837 (esophageal cancer)
 8,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accumulating data indicate a beneficial effect of combining infusional fluorouracil (5-FU) with radiation therapy in gastrointestinal cancers, and phase II/III studies are under way to examine this approach in a variety of tumor types. The oral fluoropyrimidine capecitabine (Xeloda) provides a more convenient approach to radiosensitization. The agent has good single-agent activity in a variety of tumor types. The final step in activation of the drug to 5-FU occurs via activity of thymidine phosphorylase; thymidine phosphorylase activity is markedly upregulated in many tumor tissues compared with healthy tissue (Miwa M, Ura M, Nishida M, et al: Eur J Cancer 34:1274-1281, 1998), allowing greater accumulation of 5-FU in tumor tissue, and there is evidence indicating that radiation therapy results in augmented upregulation of this enzyme. A variety of data suggest benefits of 5-FU as a radiosensitizer in improving outcome of radiation therapy in a number of gastrointestinal cancers, including data indicating improved survival with this chemoradiation therapy approach. Prospective and randomized studies of 5-FU-based chemoradiation are under way in esophageal, gastric, biliary tract, pancreatic, rectal, and anal cancer. Early phase studies are planned to examine the combination of capecitabine, celecoxib (Celebrex), and radiation therapy in esophageal cancer and pancreatic cancer and to compare the effects of capecitabine and capecitabine/oxaliplatin (Eloxatin) with radiation therapy in rectal cancer. A phase III trial comparing capecitabine and infusional 5-FU in chemoradiation therapy in rectal cancer has also been planned. Additional studies should be conducted in gastric, biliary tract, and anal cancer. Capecitabine shows promise in replacing infusional 5-FU as the platform for gastrointestinal chemoradiation therapy.
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PMID:Capecitabine and radiation therapy for advanced gastrointestinal malignancies. 1252 Jun 37

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

Esophageal cancer frequently expresses cyclooxygenase-2 (COX-2) enzyme. In preclinical studies, COX-2 inhibition results in decreased cell proliferation and potentiation of chemotherapy and radiation. We report preliminary results of a phase II study conducted by the Hoosier Oncology Group in patients with potentially resectable esophageal cancer. All patients received cisplatin at 75 mg/m2 given on days 1 and 29 and fluorouracil (5-FU) at 1000 mg/m2 on days 1 to 4 and 29 to 32 with radiation (50.4 Gy beginning on day 1). Celecoxib (Celebrex) was administered at 200 mg orally twice daily beginning on day 1 until surgery and then at 400 mg orally twice daily until disease progression or unexpected toxicities, or for a maximum of 5 years. Esophagectomy was performed 4 to 6 weeks after completion of chemoradiation. The primary study endpoint was pathologic complete response (pCR). Secondary endpoints included response rate, toxicity, overall survival, and correlation between COX-2 expression and pCR. Thirty-one patients were enrolled from March 2001 to July 2002. Respective grade 3/4 toxicities were experienced by 58%/19% of patients, and consisted of granulocytopenia (16%), nausea/vomiting (16%), esophagitis (10%), dehydration (10%), stomatitis (6%), and diarrhea (31%). Seven patients (24%) required initiation of enteral feedings. There have been seven deaths so far, resulting from postoperative complications (2), pulmonary embolism (1), pneumonia (1), and progressive disease (3). Of the 22 patients (71%) who underwent surgery, 5 had pCR (22%). We conclude that the addition of celecoxib to chemoradiation is well tolerated. The pCR rate of 22% in this study is similar to that reported with the use of preoperative chemoradiation in other trials. Further follow-up is necessary to assess the impact of maintenance therapy with celecoxib on overall survival.
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PMID:Cisplatin, fluorouracil, celecoxib, and RT in resectable esophageal cancer: preliminary results. 1568 29