Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009402 (colorectal cancer)
 53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown clinical activity in metastatic colorectal cancer patients when used as either a first-line or second-line treatment. Here, we evaluated the efficacy and safety of bevacizumab plus FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) or FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin) in metastatic colorectal cancer cases after failure to FOLFIRI and FOLFOX. Between October 2004 and February 2007, the data on 42 patients with metastatic colorectal cancer after failure of FOLFIRI and FOLFOX were reviewed retrospectively. All patients were treated with bevacizumab plus FOLFIRI or FOLFOX. The median patient age was 57.0 years. The ECOG performance status was 0 or 1 in 27 patients (64.3%). The number of previous chemotherapy regimens was >/=3 in 35 patients (83.3%). Thirty-nine patients were evaluable for response. Four patients had partial responses (PRs) and no patient had a complete response (CR), giving an overall response rate of 9.5%. Twenty-two patients (52.4%) had stable disease and 13 patients (31.0%) showed progressive disease. With a median follow-up time of 12.9 months (range 1.0-30.0 months), the median progression-free survival time and the median overall survival time were 5.3 and 9.5 months, respectively. Grade 3 or 4 neutropenia developed in 18 patients (42.9%), including febrile neutropenia in 4 patients (9.5%). Common non-hematologic toxicities were fatigue (21.4%), neuropathy (21.4%), and mucositis (21.4%). Grade 2 or 3 hypertension occurred in 4 patients (9.6%), and grade 1 or 2 proteinuria was seen in 16 patients (38.1%). The frequencies of adverse events related BV, such as bleeding, thrombosis, and gastrointestinal perforation, were within the ranges of previous reports. However, there were no treatment-related deaths. The combination of bevacizumab plus FOLFIRI or FOLFOX showed modest activity and was relatively tolerable in patients with metastatic colorectal cancer refractory to both FOLFIRI and FOLFOX.
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PMID:Bevacizumab plus FOLFIRI or FOLFOX as third-line or later treatment in patients with metastatic colorectal cancer after failure of 5-fluorouracil, irinotecan, and oxaliplatin: a retrospective analysis. 1849 64

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

Ulcerative colitis is a chronic inflammatory bowel disease, often associated with abdominal pain, rectal bleeding, fatigue, and poor quality of life. Although 5-aminosalicylic acid (5-ASA) preparations are the mainstay of treatment of this condition, the observed efficacy of many current formulations is limited by delivery systems that require multiple-daily dosing schedules and are associated with poor patient adherence. It is of critical importance that patients adhere to medication regimens, because failure to do so has been shown to result in a greater number of disease flares and an increased risk of complications, including colorectal cancer. Patient-friendly formulations of 5-ASA have recently been approved or are in development to overcome the limitations of many older formulations and improve remission rates. As a major point of contact for many patients with ulcerative colitis, it is essential that gastrointestinal nurses keep abreast of such relevant developments in treatment options. Indeed, nurses are a crucial educational conduit for patients and are in a unique position to serve as trusted educators on important issues. This review provides an update on recent advances in 5-ASA therapy to ensure that gastrointestinal nurses are aware of potential strategies for improving clinical outcomes of patients with ulcerative colitis.
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PMID:Novel 5-aminosalicylic acid formulations in ulcerative colitis: old dog, new tricks. 1870 33

Pain (P), fatigue (F), and insomnia (I) are among the most prevalent, distressing, and undermanaged symptoms experienced by cancer patients. Research has demonstrated that PFI co-occur; what remain unclear are the patterns and stability of PFI and the patient, disease, and treatment characteristics that predict PFI patterns over time. This secondary analysis used a data set composed of 867 elders (46% women) who were newly diagnosed with breast, colorectal, lung, or prostate cancer and followed at 4 points during the year after diagnosis. The university's institutional review board approved this study. Descriptive statistics and multistate transition models using multinomial logistic regression were used. The typical participant was 72.6 years old, who reported 7.9 symptoms and 2.7 comorbidities. Previous PFI pattern was consistently associated with significantly increased risks of subsequent PFI pattern. At observations 1 to 3, lung cancer, treatment, higher comorbidity with breast cancer, and late-stage colorectal cancer were significantly associated with increased risks of PFI patterns. Advancing age was not significantly associated with increased risks of PFI patterns. Pain, fatigue, and insomnia co-occurrence declined over time but was associated with significantly increased risks of death or loss to follow-up and increased reports of other symptoms. Pain, fatigue, and insomnia co-occurrence is associated with adverse outcomes and should be proactively targeted for intervention.
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PMID:Predictors of patterns of pain, fatigue, and insomnia during the first year after a cancer diagnosis in the elderly. 1877 57

The combination of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX-4) is still a reference regimen in advanced colorectal cancer; however, the addition of new biologic compounds represents a significant way forward. Bortezomib is an inhibitor of proteasome, a multicatalytic enzyme complex that degrades several intracellular proteins. In this study, escalating doses of Bortezomib were administered along with the standard FOLFOX-4 doses, in order to evaluate the dose-limiting toxicity (DLT), toxicity profile and activity of the combination. Patients with advanced colorectal cancer, unpretreated for metastatic disease, were enroled in the study. Bortezomib starting dose was 1.3mg/m(2), which was to be escalated in the subsequent steps according to the toxicities observed after first cycle. Exploratory pharmacogenetics research was conducted by analysing the association between clinical outcomes and polymorphisms in candidate genes for response to each of the used drugs. Correlation between tumour marker changes and response was also investigated. One mg/m(2) (DL-1) was defined as being the maximum tolerated dose since only 1 DLT was observed in 6 patients. The main toxicities were haematologic, neuropathy, diarrhoea and fatigue. Amongst 13 evaluable patients, five had a partial response, five had a stable disease and three patients progressed. Two patients are long-term survivors after a combined chemosurgical approach. Further trials of the current combination may be justified.
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PMID:An EORTC phase I study of Bortezomib in combination with oxaliplatin, leucovorin and 5-fluorouracil in patients with advanced colorectal cancer. 1880 14

Three-drug combination of fluoropyrimidine, irinotecan and oxaliplatin has shown survival benefits in patients with metastatic colorectal cancer (mCRC). Recently we performed a phase II study of a new 3-drug regimen, TIROX (S-1 plus irinotecan and oxaliplatin) to evaluate efficacy and safety in refractory mCRC patients. Patients with refractory to all of 3 drugs, age > or = 18 years, PS 0-2, > or = 1 measurable lesion(s) and adequate organ functions were eligible. S-1 was given 40 mg/m(2) twice a day on D1-14, oxaliplatin 85 mg/m(2) and irinotecan 150 mg/m(2) on D1 every 3 weeks. The primary endpoint was overall response rate (ORR). Between Mar 2007 and Nov 2007, 19 patients (of 18 planned) were enrolled; median age 50 years; M/F 12/7; PS 0/1/2 5/13/1; colon/rectum 11/8. By intent-to-treat analysis, ORR was 21.1% (95% CI, 8.7-43.7) and disease control rate was 52.6% (95% CI 31.5-72.8) with four PRs and six SDs. Median duration of disease control was 4.3 months (95% CI 1.7-6.9). Median PFS was 2.6 months (95% CI 2.2-2.9) and median OS was 9.8 months (95% CI 5.3-14.4) after median F/U of 15.4 months. G3/4 toxicities per pt included neutropenia (five, 26.3%), febrile neutropenia (two, 10.5%), thrombocytopenia (one, 5.3%), diarrhea (two, 10.5%) and fatigue (two, 10.5%). TIROX seemed to be feasible and efficacious for refractory mCRC patients, and could be an alternative for patients with good PS but no further treatment options.
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PMID:A phase II study of S-1 plus irinotecan and oxaliplatin in heavily-treated patients with metastatic colorectal cancer. 1881 28

While the use of chemotherapy has significantly improved survival rates, the symptoms associated with chemotherapy remain a major burden for patients. Preventing or appropriately managing side effects significantly improves patients' functional status and quality of life, ultimately leading to greater patient acceptance of chemotherapy. However, symptom assessment and management are fraught with difficulties such as poor patient recall, retrospective assessment conducted by clinicians and lack of appropriate, clinically relevant and patient friendly symptom assessment and management tools. Furthermore the differences between clinician and patient perceptions of stresses and distress during chemotherapy are well recognised. This study aimed to evaluate the impact of a nursing intervention incorporating structured symptom assessment and management, facilitated by information technology, on chemotherapy-related symptoms, nausea, vomiting, fatigue and mucositis. This pan-European study, involved 8 clinical sites from Belgium, Denmark, England, Ireland and Scotland. Adults (n=249) receiving first line chemotherapy for breast, lung, ovarian or colorectal cancer, osteosarcoma, acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) or lymphoma were recruited to the study. Patients completed daily symptom assessment questionnaires for 14 days following consecutive cycles of chemotherapy. Symptom outcomes were compared before and after the introduction of the intervention with positive impact on patients' experiences of nausea, vomiting and oral problems. Fatigue was not significantly improved.
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PMID:WISECARE+: Results of a European study of a nursing intervention for the management of chemotherapy-related symptoms. 1884 57

The present study was designed to retrospectively examine the efficacy of postoperative adjuvant chemotherapy in 107 patients with stage II primary colorectal cancer who underwent curative resection. The chemotherapy regimen was intravenous 5FU/LV in 30 patients (FL-IV group) and oral UFT/PSK in 77 patients (oral group). There were no significant differences between the FL-IV and the oral group with respect to the 3-year relapse-free survival rate, 5-year relapse-free survival rate, and 5-year overall survival rate, which were 82.4 vs. 83.0% (p=0.8546), 78.8 vs. 80.0% (p=0.756), and 81.6 vs. 92.8% (p=0.1609), respectively. Grade 3 adverse events that occurred in the FL-IV group were leukopenia in one patient (3.3%), nausea/vomiting in two (6.6%), anorexia in two (6.6%), diarrhea in one (3.3%), and fatigue in one (3.3%). No grade 3 or 4 adverse events were observed in the oral group. These results suggest that the oral regimen achieved equivalent efficacy to the FL-IV regimen in patients with stage II colorectal cancer, while improving their postoperative quality of life.
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PMID:Comparison between intravenous and oral postoperative adjuvant immunochemotherapy in patients with stage II colorectal cancer. 1894 20

The rest-activity circadian rhythm (CircAct) reflects the function of the circadian timing system. In a prior single-institution study, the extent of CircAct perturbation independently predicted for survival and tumor response in 192 patients receiving chemotherapy for metastatic colorectal cancer. Moreover, the main CircAct parameters correlated with several health-related quality of life (HRQoL) scales. In this prospective study, we attempted to extend these results to an independent cohort of chemotherapy-naive metastatic colorectal cancer patients participating in an international randomized phase III trial (European Organisation for Research and Treatment of Cancer 05963). Patients were randomized to receive chronomodulated or conventional infusion of 5-fluorouracil, leucovorin, and oxaliplatin as first-line treatment for metastatic colorectal cancer. Patients from nine institutions completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and wore a wrist accelerometer (actigraph) for 3 days before chemotherapy delivery. Two validated parameters (I<O and r24) were used to estimate CircAct. Of 130 patients with baseline CircAct assessments, 96 had baseline HRQoL data. I<O was confirmed to correlate with global quality of life, physical functioning, social functioning, fatigue, and appetite loss (r > |0.25|; P < 0.01). I<O further independently predicted for overall survival with a hazard ratio of 0.94 (P < 0.0001). The associations between CircAct parameters, HRQoL, and survival, which were shown in this international study involving previously untreated metastatic colorectal cancer patients, confirm prior single-institution findings in mostly pretreated metastatic colorectal cancer patients. The circadian timing system constitutes a novel therapeutic target. Interventions that normalize circadian timing system dysfunction may affect quality of life and survival in cancer patients.
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PMID:Circadian rhythm in rest and activity: a biological correlate of quality of life and a predictor of survival in patients with metastatic colorectal cancer. 1947 Jul 69

Colorectal cancer is a common disease in the United States. The majority of sporadic colorectal cancers develop from adenomatous polyps. In the United States, the incidence of colorectal cancer is declining, most likely because of colonoscopic polypectomy. Adenoma detection rate is affected by the quality of prep, careful mucosal inspection, and withdrawal time. In this issue of the Journal, there is intriguing evidence that the timing of colonoscopy, morning vs. afternoon, affects adenoma detection rate. Physician fatigue is postulated as a factor leading to lower polyp detection rates in the afternoon compared with the morning. Further, prospective studies are needed to confirm these findings and determine the effect on clinical practice.
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PMID:The influence of timing of colonoscopy on adenoma detection: is timing everything? 1949 41


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