Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relatively high response rate demonstrated with the use of continuous infusion 5-Fluorouracil (CIFU) 200 to 300 mg/m2 per day in disseminated colon cancer is the rationale behind a NCI-sponsored intergroup trial (INT 0153) for postoperative adjuvant therapy of stage III colon cancer. Because CIFU necessitates a significant reduction in the dose of the modulator leucovorin compared with bolus 5-FU, a pilot study of continuous infusion 5-FU in several doses with levamisole was conducted to determine any unexpected toxicity of this combination, and to assess completion rates of levamisole was conducted to determine any unexpected toxicity of this combination, and to assess completion rates of this dose intensive schedule. CIFU, scheduled as two 12-week cycles, was administered at 250 mg/m2 per day. Pending toxicity at the initial dose, CIFU was to be escalated (300 mg/m2) or de-escalated (200 mg/m2). All but one patient entered on this trial completed 24 weeks of adjuvant CIFU+levamisole. Eight patients (57%) completed 24 weeks of therapy with the 2-week scheduled break. One of these 8 patients required a dose reduction without interrupting the schedule. Six patients had toxicity from the CIFU, which obliged us to interrupt the schedule. Limiting toxicities were stomatitis and hand-foot syndrome. No dose-limiting hematologic toxicity was encountered. Three patients (21%) had catheter problems that required replacement. These data suggest that up to 30% of patients started on this regimen may require dose reduction, shorter infusion courses with rest breaks, or both to complete 24 weeks of adjuvant treatment in order to achieve desired dose intensity.
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PMID:A pilot trial of continuous infusion 5-fluorouracil with levamisole for adjuvant therapy of colon cancer. 880 55

At present there remains a need for more effective systemic therapy in advanced pancreatic cancer. Some studies have suggested that infusional chemotherapy schedules and biomodulation of 5-fluorouracil (5-FU) may improve the therapeutic outcome in advanced colon cancer. One such regimen that uses continuous infusion 5-FU, weekly leucovorin, daily dipyridamole, and intermittent mitomycin-C has activity in both colon and unresectable pancreatic carcinoma. The intent of this trial was to test the effectiveness of this four-drug regimen in advanced pancreatic cancer. Patients received 5-FU 200 mg/m2 daily by continuous infusion, leucovorin 30 mg/m2 IV weekly, mitomycin-C 10 mg/m2 day 1, and dipyridamole 75 mg orally four times daily for 5 weeks. After a 1-week break, treatment cycles were repeated every 6 weeks. Eligibility included biopsy-proven advanced measurable pancreatic cancer, Eastern Cooperative Oncology Group performance status 0 and 2, and no prior systemic chemotherapy. Of 46 evaluable patients, 9 partial responses and 1 complete tumor response were seen, for an overall response rate of 22% (95% confidence interval 11-36%). The median survival in the group of 50 patients registered to this trial was 4.6 months, with a range of 0.33 to 40.2 months. Toxicity was manageable, with the most common toxicities (> or =grade III National Cancer Institute Common Toxicity Criteria) being anorexia (13%), stomatitis (17%), and hand-foot syndrome (13%). Of note, little severe hematologic toxicity and no significant headaches were reported. Although some patients did respond, the therapeutic results are not encouraging enough to take this regimen to phase III testing.
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PMID:Phase II evaluation of continuous-infusion 5-fluorouracil, leucovorin, mitomycin-C, and oral dipyridamole in advanced measurable pancreatic cancer: a North Central Cancer Treatment Group Trial. 1103 19

Capecitabine is an orally administered fluoropyrimidine carbamate that is preferentially converted to 5-fluorouracil in tumors relative to normal tissue. Three different dosing regimens were investigated in phase I studies: continuous monotherapy, intermittent monotherapy, and intermittent therapy supplemented with leucovorin. These studies defined the maximum tolerated dose for each regimen. Dose-limiting toxicities were diarrhea, hand-foot syndrome, and leukopenia. Each phase I study recommended a dose; these were directly compared in a phase II study. This phase II study showed that the intermittent regimen of capecitabine monotherapy was the most favorable on the basis of tumor response rates, time to progression, dose intensity, and toxicities. The intermittent regimen of capecitabine has been compared with the Mayo Clinic regimen of 5-fluorouracil/leucovorin in two large, phase III studies of patients with advanced colorectal cancer. The combined data from the two studies showed that capecitabine was superior to 5-fluorouracil/leucovorin in terms of tumor response rate (22% v 13%; P < .0001) and similar in terms of time to disease progression and overall survival. Capecitabine is now being compared with the Mayo Clinic regimen as an adjuvant treatment for patients with Dukes' C colon cancer.
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PMID:5-fluorouracil/leucovorin versus capecitabine in patients with stage III colon cancer. 1127 90

The purpose of this study was to determine the safety of irinotecan and capecitabine in patients with advanced solid tumors. Thirty-four patients received 122 courses of irinotecan 200 to 300 mg/m(2) as an intravenous infusion during 30 minutes on day 1 and capecitabine 1,500 to 3,000 mg/d orally 12 hours apart starting on day 2 for 14 days, repeated every 21 days (one course). Three to seven patients were treated in six dose-escalation cohorts. Three of 7 (43%) patients treated with irinotecan 300 mg/m(2) and capecitabine 2,300 mg/d had course 1 dose-limiting toxicity (DLT) defining maximum tolerated dosage (MTD). Fatigue and diarrhea were the major DLTs, and other events included neutropenia, anorexia, and hand-foot syndrome. At one dose level below the MTD, none of 7 patients treated with irinotecan 275 mg/m(2), and capecitabine 2,300 mg/d (36 courses) had course 1 DLT. Grade III to IV toxicities beyond course 1 included neutropenia (11% of all courses), fatigue (3.4%) and hand-foot syndrome (3.4%). There were only two episodes of febrile grade II neutropenia. There were no toxic deaths. Transient antitumor response was noted in one patient with irinotecan and 5-fluorouracil-refractory colon cancer. The combination of irinotecan 275 mg/m(2) and capecitabine 2,300 mg/d represents a safe, favorable, and convenient outpatient regimen warranting further phase II evaluation.
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PMID:Phase I clinical trial of irinotecan with oral capecitabine in patients with gastrointestinal and other solid malignancies. 1239 99

The oral fluoropyrimidine capecitabine (Xeloda) delivers 5-FU to the tumour site, thereby limiting the side effects and other complications associated with intravenous (i.v.) 5-FU. As an oral drug, capecitabine is preferred to 5-FU by many patients as it can be conveniently taken at home. In first-line metastatic colorectal cancer (MCRC), capecitabine results in superior response rates and equivalent progression-free and overall survival compared with i.v. 5-FU/LV. There is also increasing evidence for replacing i.v. 5-FU with capecitabine in combination with other anticancer agents (e.g. oxaliplatin and irinotecan) in MCRC and in the adjuvant treatment of early stage colon cancer. In anthracycline-pretreated metastatic breast cancer (MBC), adding capecitabine to docetaxel improves survival, time to progression (TTP) and response rates beyond docetaxel. Single-agent capecitabine is also effective in pretreated MBC and is a promising first-line therapy. Capecitabine has a favourable safety profile, the most frequent adverse events being hand-foot syndrome, stomatitis and diarrhoea. Because capecitabine is orally administered, it is possible to intervene promptly with dose interruption/reduction to resolve adverse events without impacting on efficacy. The increasing availability of capecitabine in the home-based setting requires careful consideration of the role of the oncology nurse, who is the key link between the patient and clinician for effective and efficient management.
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PMID:Development of and clinical experience with capecitabine (Xeloda) in the treatment of solid tumours. 1534 78

The current standard adjuvant chemotherapy for suitable patients with stage III colon cancer is the combination of oxaliplatin and 5-fluorouracil plus folinic acid (5-FU/LV). However, until recently and for many years prior to this, the accepted standard adjuvant chemotherapy was 6-8 months of bolus 5-FU/LV. However, bolus treatment was associated with significant toxicity, namely stomatitis, diarrhea and neutropenia, in addition to multiple hospital visits for drug administration for patients. The X-ACT trial (Xeloda in Adjuvant Colon Cancer Therapy) compared traditional bolus 5-FU/LV (as per the Mayo Clinic regimen) with capecitabine, in the adjuvant treatment of 1987 stage III colon cancer patients. The main safety, efficacy and pharmacoeconomic results have all been published, and the updated 5-year efficacy results have also recently been presented. This trial demonstrated that capecitabine was at least as effective as bolus 5-FU/LV in terms of disease-free and overall survival, with trends towards superiority for both. Moreover, there was much less toxicity associated with capecitabine, apart from hand-foot syndrome which was significantly more prevalent. On the basis of the X-ACT trial, capecitabine was approved by the US FDA, the National Institute for Clinical Excellence and the Scottish Medicines Consortium as monotherapy for the adjuvant treatment of stage III colon cancer.
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PMID:Redefining adjuvant chemotherapy in patients with stage III colon cancer: X-ACT trial. 1840 21

Patients with colorectal cancer present a number of supportive care challenges including those related to the underlying disease, such as gastrointestinal obstruction, nausea, anorexia, and fatigue, and those caused by the treatments, such as oral mucositis, neuropathy, and chemotherapy-induced diarrhea. Unique toxicities can accompany specific routes of administration of colon cancer drugs such as hand-foot syndrome with oral capecitabine and continuous infusion fluorouracil and biliary sclerosis with intrahepatic arterial floxuridine. The newer targeted therapies also present new toxicities, such as cardiovascular events and wound-healing complications with bevacizumab and rash and hypomagnesemia with cetuximab. Recent additions to the therapeutic armamentarium have presented new challenges, such as oxaliplatin-induced peripheral neuropathy, capecitabine-induced hand-foot syndrome, cetuximab-induced rash, and bevacizumab-associated arterial thrombotic events, bowel perforation, hypertension, and wound-healing complications. This article focuses on the prevention and management of several of these more common symptoms and toxicities.
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PMID:Supportive care in the management of colon cancer. 1863 90

Capecitabine is one of the most effective oral regimens of chemotherapy against advanced or recurrent breast cancer. In addition, capecitabine could widely be used for treatment of colon cancer. It appears that more patients will be administered capecitabine because of its QOL benefits. However, Hand-Foot Syndrome(HFS)may appear to be about 50% of the patients who take this regimen. As a result, the patient's QOL is hindered and led to a reduction of the dosage or discontinuation of the treatment depending on the grade of adverse event. This time, we evaluated the efficacy of topical emollients, creams and vitamin B6 for prevention and reduction of HFS symptoms for patients who received capecitabine. We found the efficacy of preventative measures that the occurrence of HFS grade 1 or above could be decreased and delayed. We also noticed that these preventative measures appear to be decreased the occurrence of HFS grade 2 or above, which led to a reduction of dosage or discontinuation of the treatment. For continuation and completion of the treatment and securing of patient's QOL, the supportive measures are needed to control a variety of side effects, such as HFS and others, and a team care support is indispensable.
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PMID:[Management of hand-foot syndrome in patient treated with capecitabine]. 1870 48

The patient was a 78-year-old woman who suffered from right upper quadrant pain. She was diagnosed as colon cancer with hepatic metastasis. Initial chemotherapy using capecitabine plus oxaliplatin(XELOX)+bevacizumab achieved partial response. After 12 months, XELOX was discontinued due to Grade 3 hand-foot syndrome and peripheral neuropathy. Irinotecan plus oral S-1(a combination of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate)and(IRIS)+bevacizumab were continued as second-line therapy, and her status was maintained as stable disease. XELOX and IRIS regimens do not require catheter placement and long infusion process, providing a great advantage to patients.
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PMID:[A case of metastatic colon cancer effectively treated by XELOX and IRIS]. 2386 64

A regimen of capecitabine plus oxaliplatin(XELOX)has become one of the standard postoperative adjuvant chemotherapies for colon cancer. However, few tolerability studies have been conducted in Japan. In this study, we retrospectively examined treatment continuation and the adverse events that occurred during 8 courses of postoperative adjuvant chemotherapy with XELOX in 21 patients with colorectal cancer who had undergone curative resection. The completion rate for 8 courses of treatment with XELOX was 71.4%, while the median relative dose intensities of capecitabine and oxaliplatin were 85.0% and 75.0%, respectively. Although the incidence of subsequent Grade 3 or higher hand-foot syndrome was 14.3%, the rate of peripheral neuropathy was 0%. Our hospital had a high rate of XELOX treatment continuation, suggesting that XELOX adjuvant chemotherapy would be well tolerated in clinical practice as well.
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PMID:[Tolerability of XELOX in postoperative adjuvant chemotherapy for colorectal cancer]. 2512 86


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