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)

This study identified the psychosocial problems that 752 patients from 3 states who had been diagnosed with 1 of the 10 most commonly occurring cancers indicated concerned them the most. Approximately 1 year after being diagnosed with cancer, 68.1% of patients were concerned with their illness returning, and more than half were concerned with developing a disease recurrence (59.8%) or had fears regarding the future (57.7%). In addition to these psychological problems focused on fear, approximately two-thirds (67.1%) of patients were concerned about a physical health problem, fatigue, and loss of strength. Two other physical health problems that concerned more than two-fifths of patients were sleep difficulties (47.9%) and sexual dysfunction (41.2%). More problems were reported by younger survivors (ages 18-54 yrs), women, nonwhites, those who were not married, and those with a household income of less than 20,000 US dollars a year. Those patients currently in treatment for cancer reported on average significantly more problems (P < 0.001) and on average had a higher Cancer Problems in Living Scale (CPILS) total score (P < 0.001) compared with those not currently in treatment. In a comparison of respondents with one of the four most common cancers, the most concerns regarding problems in living and highest mean CPILS scores were reported by those diagnosed with lung cancer, followed by survivors of breast cancer, colorectal cancer, and prostate cancer.
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PMID:Adult cancer survivors: how are they faring? 1625 29

Thirty-one patients with metastatic colorectal cancer were enrolled in this phase I/II trial of a triple combination of camptosar (C), oxaliplatin (O) and tomudex (T), all given on day one of a convenient three-week schedule. Patients received 257 cycles (1-18) in five cohorts. Toxicity was manageable and haematological toxicity was mild to moderate. Diarrhoea was the main dose-limiting toxicity; nausea and vomiting were common. Fatigue was frequent, moderate in severity and a reason for discontinuation in some patients. The recommended phase II doses were (C) 220 mg/m(2), (O) 100mg/m(2), (T) 2.75 mg/m(2). A 50% response rate in 30 evaluable patients was confirmed by an independent radiology review board; progression-free survival and overall median survival were 7.3 months and 16.6 months, respectively. Of the 16 patients treated at the recommended dose, 9 (56.3%) experienced partial response. Further evaluation in a randomized study compared to sequential doublets is warranted. Triple combinations could be relevant in curative settings for high-risk patients.
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PMID:A National Cancer Institute of Canada Clinical Trials Group Study--IND.135: Phase I/II study of irinotecan (camptosar), oxaliplatin and raltitrexed (tomudex) (COT) in patients with advanced colorectal cancer. 1633 Feb 4

Primary sclerosing cholangitis (PSC) is a chronic cholestatic syndrome of unknown etiology frequently associated with inflammatory bowel disease and characterized by diffuse inflammation and fibrosis of the intra and/or extrahepatic bile ducts. Recent studies seem to favor autoimmunity in the context of a genetic predisposition as the most likely underlying mechanism for the development of the disease, however our knowledge on the pathogenesis of PSC is still incomplete and further work is needed. The most common manifestations are fatigue, pruritus, jaundice and abdominal pain; however, the increasing use of invasive cholangiography has led to diagnosing this condition in a high proportion of asymptomatic patients. PSC usually follows a progressive course leading to biliary cirrhosis with complications of portal hypertension and hepatic failure. Patients with PSC also may develop a number of other complications, including bacterial cholangitis, dominant biliary strictures, conditions of chronic cholestasis, colorectal cancer and cholangiocarcinoma. Currently, no medical therapy aimed at disrupting disease progression is available, although high-dose ursodeoxycholic acid and other medicines are being evaluated in clinical trials. A better understanding of the pathogenesis of the disease will serve as a guide for evaluating new medical approaches. Liver transplantation is the only therapeutic alternative that improves survival in patients with end-stage PSC. Prognostic models are useful in determining the timing of liver transplantation.
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PMID:Primary sclerosing cholangitis. 1648 1

The epidermal growth factor receptor (EGFR), which participates in signalling pathways that are deregulated in cancer cells, is frequently mutated in colorectal-cancer cells. Cetuximab is a monoclonal antibody that specifically blocks the EGFR. We evaluated the efficacy of cetuximab in weekly combination with irinotecan in metastatic colorectal cancer patients refractory to previous treatments based on oxaliplatin or irinotecan. We included 55 heavily pretreated patients (colon/rectum: 34/11, M/F: 16/29, median age 63 years, range: 27-79) whose disease had progressed during or within an oxaliplatin-based first-line chemotherapy and a irinotecan-based second-line regimen. Patients were followed for tumour response and were also evaluated for the time to tumour progression, and safety of treatment. Cetuximab was given at an initial dose of 400 mg m(-2), followed by weekly infusions of 250 mg m(-2). Irinotecan was administered weekly at the dose of 90 mg m(-2). All patients were assessable for treatment efficacy and safety response rate was 25.4% (95% CI: 21.7-39.6%); 38.2% (95 CI: 18.6-39.8%) of patients showed a disease stability as the best response. As a consequence, the overall tumour control rate was 63.6% (95% CI: 46.4-70.6%). The median time to progression was 4.7 months (95% CI: 2.5-7.1 months) and the median survival time was 9.8 months (95% CI: 3.9-10.1 months). The most common G3-4 noncutaneous side toxicities were: diarrhoea (16.4%), fatigue (12.7%) and stomatitis (7.3%). 89.1% of patients developed skin toxicity and 32.6% of cases was of grade 3-4. No allergic reactions were identified at any courses in any patients. Fever was documented in 27.3% of patients and was most commonly recorded after the first administration. Cetuximab has clinically significant activity even in heavily pretreated colorectal cancer patients progressed after both oxaliplatin and irinotecan-based chemotherapy regimens.
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PMID:Cetuximab and irinotecan as third-line therapy in advanced colorectal cancer patients: a single centre phase II trial. 1650 34

The purpose of this study was to evaluate the safety and activity of fixed-dose capecitabine in patients with advanced colorectal cancer and to correlate pretreatment plasma concentrations of homocysteine and serum and red cell folate with toxicity. Patients received capecitabine 2000 mg (4 x 500 mg tablets) twice daily on days 1-14 every 3 weeks. They were reviewed weekly during the first cycle and then three weekly for safety assessment. Eligibility criteria were advanced/metastatic colorectal cancer, < or = 2 prior chemotherapy regimens, ECOG performance status 0-2 and life expectancy >12 weeks. A total of 60 patients were enrolled and 55 were evaluable for efficacy. The median age was 72 years and 63% of patients had a performance status of 1 or 2. Confirmed tumour responses were reported in 15 patients (28%; 95% confidence interval (CI), 15.7-40.3%). The median time to disease progression was 4.9 months and median overall survival was 11.2 months. The median ratio of fixed dose to body surface area (BSA)-calculated dose was 88% (range 65-108%). Significant myelosuppression was not observed. Grade 2/3 treatment-related adverse events were diarrhoea (34%), fatigue (27%), stomatitis (15%) and hand-foot syndrome (22%). Dose reduction due to adverse events was required in 16 patients (29%) and multiple reductions in five patients (9%). There was no grade 3/4 haematological toxicity, any grade 4 adverse events or treatment-related deaths. Patients with higher pretreatment levels of serum folate experienced significantly greater toxicity (P = 0.02, CI: 1.0-1.2) during cycle 1 and over the entire treatment period (P = 0.04, CI: 1.0-1.3). Pretreatment homocysteine concentrations did not predict for toxicity. In conclusion, fixed-dose capecitabine appears to have similar efficacy and safety compared to the currently recommended dose schedule based on body surface area and simplifies drug administration. A high pretreatment folate may be predictive of increased toxicity from capecitabine.
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PMID:A phase II study of fixed-dose capecitabine and assessment of predictors of toxicity in patients with advanced/metastatic colorectal cancer. 1655 36

In a large, 16-week, prospective study of 2,964 anemic patients with various cancers undergoing chemotherapy, once-weekly subcutaneous administration of 40,000 U of epoetin alfa,with potential escalation to 60,000 U, increased hemoglobin (Hgb) levels, decreased transfusion requirements, and improved quality of life (QOL) as assessed using the Linear Analog Scale Assessment (LASA) for energy, activity, and overall QOL and the Functional Assessment in Cancer Therapy-Anemia (FACT-An) QOL instrument. A retrospective subset analysis conducted in 244 colorectal cancer patients enrolled in the study showed statistically significant improvements from baseline to final readings in LASA energy, activity, and overall QOL and FACT-An Anemia Symptoms and Fatigue subscale scores (P < 0.02). Moreover, patients who achieved larger improvements in Hgb levels also demonstrated greater percentage improvements in QOL over baseline measurements. Mean Hgb levels increased by 1.2 g/dL after 4 weeks of treatment and by 1.6 g/dL by study end, independent of red blood cell transfusion within 28 days prior to the Hgb assessment. Hematopoietic response (Hgb level > or = 12 g/dL and/or increase in Hgb level > or = 2 g/dL, independent of transfusion) was observed in 61% of patients (139/229). Additionally, the proportion of patients receiving transfusions decreased from 17% at baseline to 4% during the final month of therapy. Epoetin alfa was well tolerated, with no evidence of unexpected adverse events. Except for significantly higher QOL scores at baseline, results for the cohort of colorectal cancer patients were similar to those for patients with other cancer types in the main study population.
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PMID:Clinical benefits of once-weekly epoetin alfa in anemic patients with colorectal cancer receiving chemotherapy. 1672 48

Computed tomographic (CT) colonography is a promising noninvasive examination for colorectal cancer screening; however, the optimal interpretation strategy remains undecided. Virtual dissection is an innovative technique whereby the three-dimensional (3D) model of the colon is virtually unrolled, sliced open, and displayed as a flat 3D rendering of the mucosal surface, similar to a gross pathologic specimen. This technique has the potential to reduce evaluation time by providing a more rapid 3D image assessment than is possible with an antegrade and retrograde 3D endoluminal fly-through. It may also ultimately improve accuracy by reducing blind spots present with 3D endoluminal displays and by reducing reader fatigue. A disadvantage of virtual dissection is the potential for distortion of colonic lesions and normal anatomy. To avoid potential pitfalls in image interpretation, the radiologist must be familiar with the unique appearance of the normal colon anatomy and of various pathologic findings when using virtual dissection with two-dimensional axial and 3D endoluminal CT colonographic image data sets.
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PMID:Three-dimensional virtual dissection at CT colonography: unraveling the colon to search for lesions. 1710 43

Oxaliplatin (L-OHP) has been established as a key drug for advanced colorectal cancer, and combination therapy with 5-FU/Leucovorin (LV)(FOLFOX regimen) is commonly used in Europe and the US. A phase I study of modified (m) FOLFOX 6 therapy was conducted to determine the recommended dose (RD) of 5-FU infused for 46 hours. Inclusion criteria were unresectable advanced colorectal cancer,measurable lesions, performance status (PS; ECOG) 0-2, age 20-75 years, and adequate organ functions. L-OHP and l-LV was administered over 2 hours and followed by bolus injection and continuous infusion of 5-FU for 46 hours every 2 weeks. Two cycles of mFOLFOX 6 therapy were performed. Doses of L-OHP, l-LV, and bolus injection of 5-FU were fixed at 85 mg/m(2), 200 mg/m(2), and 400 mg/m(2), respectively. The dose of continuous infused 5-FU was escalated from 1,600 mg/m(2), (level 1), 2,000 mg/m(2), (level 2), 2,400 mg/m(2), (level 3), and 2,800 mg/m(2), (level 4). RD was determined in a dose escalation manner, and safety was evaluated according to NCI-CTC Ver 2.0. A total of 13 patients were enrolled. Male/female=7/6, PS 0/1/2=2/4/7, mean age 64 years (range 55-75). Thrombocytopenia was not observed, and grade 2 of neutropenia and peripheral neuropathy was observed in 4 and 6 out of 13 patients. No dose-limiting toxicity (DLT) was observed at level 1 (n=3), 2 (n=4), and 3 (n=4), but at level 4 (n=2), 2 patients experienced DLT; grade 3 easy fatigue and anorexia required treatment delay over 7 days. Level 3 was therefore determined as RD. A phase II study is ongoing to evaluate the efficacy of mFOLFOX 6 therapy.
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PMID:[A phase I study of modified FOLFOX 6 therapy for advanced colorectal cancer]. 1730 27

We evaluated the efficacy and safety of modified FOLFIRI for patients with refractory advanced or recurrent colorectal cancer. Modified FOLFIRI was given 29 patients (21 men and 8 women, with a median age of 61.0 years) from 2 to 16 times (median 10.0). 19 out of 29 patients were colon cancer, and the other 10 were rectal cancer. 18 patients were administered as first-line chemotherapy, and 11 were more than second line. CPT-11 was administered at a dose of under 150 mg/m(2), to remain within the limits in Japan. The response to treatment was CR in 3 patients, PR in 8, and SD in 12. The response rate was 37.9%. Grade 4 hematologic toxicities included leukocytopenia in 2 patients, neutropenia in 7 and anemia in 1. Grade 3/4 non-hematologic toxicities included febrile neutropenia in 4 patients, anorexia in 3, fatigue in 3, and nausea, diarrhea and interstitial pneumonia in 1. Except in 2 patients, all reactions could be controlled with the use of G-CSF or by setting drug holiday. In summary, modified FOLFIRI is a safe and effective regimen even at a dose of under 150 mg/m(2), of CPT-11. It can be given with good tolerance for patients with refractory advanced or recurrent colorectal cancer on an outpatient basis with due care especially for neutropenia.
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PMID:[Feasibility of modified FOLFIRI regimen for patients with refractory advanced or recurrent colorectal cancer]. 1730 28

The purpose of this study was to examine the efficacy of a combination treatment of sequential irinotecan and doxifluridine, an intermediate of capecitabine, evaluated by the response rate and safety in patients with metastatic colorectal cancer. In all, 60 metastatic colorectal cancer patients with measurable disease were enrolled. The schedule of the treatment consisted of a 90 min intravenous (IV) infusion of irinotecan 150 mg/m2 for on days 1 and 15, and 600-1,000 mg/body of oral doxifluridine on days 3-14 and 17-28. Cycles were repeated every 35 days. A median of three cycles of the combination therapy (range 1-14 cycles) was administered. A total of 57 patients (95%) completed at least two cycles of the therapy without any dose reductions. There was one complete response and 23 partial responses with an overall response rate of 40% [95% confidence interval (CI): 28-53%]. A total of 19 patients had stable disease, 43(72%) achieved disease control. The median time to progression was 5.9 months and the median overall survival was 20.5 months. Ten (17%) and 17 (28%) patients developed Grade 3-4 leukopenia and neutropenia, respectively. Grade 3-4 fatigue was observed in 7(12%) patients, nausea in five (8%), vomiting in four (7%), and diarrhea,in three (5%) patients. No treatment-related deaths were noted during the study. From these results, the combination of sequential irinotecan and doxifluridine is considered to be an effective, easy-to-administer regimen with acceptable tolerability.
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PMID:A phase II study of irinotecan in combination with doxifluridine, an intermediate form of capecitabine, in patients with metastatic colorectal cancer. 1742 30


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