Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thymidylate synthase (TS) expression has been identified as an important predictor of response to 5-fluorouracil (5-FU). However, there is relatively little information on the heterogeneity of TS mRNA expression between primary and metastatic tumors, as well as differential expression of TS mRNA in metastatic sites. In this study, TS mRNA expression was measured in primary colorectal cancer tumors and various metastatic tumors. The median TS/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA ratio was 0.98 in primary tumors, 0.70 in liver metastases, 1.92 in lymph node metastases, and 3.42 in pulmonary metastases. A significantly higher expression of TS mRNA was observed in pulmonary and lymph node metastases compared with their respective primary tumors. In contrast, TS mRNA expression in hepatic metastases was significantly lower than in primary tumors. Similar results were observed in tumors obtained from the same patient. These results may explain the difference in the clinical response to 5-FU-based chemotherapy between various metastatic sites. The discordant TS expression between primary and metastatic tumors is a critical factor that must be taken into account when TS is being used as a predictive biomarker for the antitumor effect of 5-FU-based chemotherapy.
Clin Colorectal Cancer 2001 Nov
PMID:Thymidylate synthase gene expression in primary colorectal cancer and metastatic sites. 1245 Apr 24

Coadministration of eniluracil with 5-fluorouracil (5-FU) allows the oral absorption of small doses of 5-FU, resulting in therapeutic plasma levels. A phase II clinical trial of this combination using a continuous dosing schedule was carried out in patients with metastatic colorectal cancer. Fifty-three previously untreated patients and 46 patients who had received one prior regimen for metastatic disease were enrolled. Patients received 10 mg/m2 of eniluracil and 1 mg/m2 of 5-FU twice daily for 28 days, with cycles repeated after a 7-day rest until progression of disease or prohibitive toxicity. Seven of 53 previously untreated patients had an objective tumor response (13.2%): 1 complete response and 6 partial responses. The mean duration of response was 6.3 months. Only 1 of the 45 evaluable patients in the previously treated group had a partial response, with no complete responses. The duration of response was 3 months. The median progression-free survival was 3.4 months for the previously untreated group and 2.5 months for the previously treated group. Median overall survival was 11.1 months for the previously untreated group and 9.0 months for the previously treated group. Hematologic toxicity was infrequent, with 3 patients experiencing grade 3 toxicity. Incidence of grade 3/4 toxicity included 11 patients with diarrhea, 5 with nausea, and 4 with vomiting. Other common toxicities included anemia and stomatitis, but they were generally mild. This regimen is well tolerated and shows activity in previously untreated patients with metastatic colorectal cancer that is similar to that observed with other 5-FU-based regimens. This regimen has not shown to be effective in patients who have had prior chemotherapy.
Clin Colorectal Cancer 2002 May
PMID:Eastern Cooperative Oncology Group phase II trial (E4296) of oral 5-fluorouracil and eniluracil as a 28-day regimen in metastatic colorectal cancer. 1245 37

For rectal cancer, local recurrence following surgical treatment is a grave complication that occurs in as many as 25% of cases. Pathological examination of the surgical resection specimen plays a primary role in assessing both the surgery- and tumor-related factors that contribute to the risk of recurrence. Among the tumor-related factors, stage has long been considered the single most accurate indicator of survival. However, recent evidence strongly suggests that the most powerful predictor of both local recurrence and overall outcome in the absence of distant metastatic disease is the macroscopic quality of the mesorectum in the resection specimen and the proximity of the tumor to the circumferential (radial) resection margin. Additional pathologic features have been shown to have stage-independent prognostic significance in colorectal cancer and may help to further define risk of adverse outcome. Such features include: tumor grade; histologic type; extent of extramural penetration by tumor; neural, venous, and/or lymphatic invasion; tumor border configuration; tumor budding; and host lymphoid response. The predictive value of tumor-specific molecular features is currently under investigation and may help to further improve prognostication and refine individual patient management in rectal cancer.
Clin Colorectal Cancer 2002 Nov
PMID:Pathologic prognostic factors in the recurrence of rectal cancer. 1248 31

Metastatic colorectal cancer is a major cause of cancer-related mortality. Surgical resection of all known metastatic disease can be curative in selected patients. The majority of patients, however, require the consideration of systemic chemotherapy as optimal palliative treatment for their diseases. Using new effective chemotherapeutic agents such as irinotecan and oxaliplatin has resulted in a clear and clinically significant improvement in survival for patients with metastatic colorectal cancer. The optimal sequences and combinations of these agents as initial and salvage chemotherapy along with 5-fluorouracil (5-FU) and leucovorin are controversial. It seems clear that it is important for all patients to have access to all 3 drugs at some point in their therapy for optimal results. Recent randomized trials of first-line chemotherapy for metastatic colorectal cancer in which patients were likely to have access to all 3 effective drugs demonstrated median survivals of 18-20 months. This compares favorably to median survivals of approximately 12 months for patients treated with 5-FU-based regimens alone prior to the availability of effective salvage therapy. A small but meaningful number of patients might develop resectable disease with curative intent as the result of significant tumor response to combination chemotherapy. Herein, we review recent developments in combination and sequential chemotherapy for metastatic colorectal cancer and the implications for the optimal treatment in these patients.
Clin Colorectal Cancer 2002 Nov
PMID:Perspectives on the role of sequential or combination chemotherapy for first-line and salvage therapy in advanced colorectal cancer. 1248 33

Locoregional therapies are useful in treating patients with colorectal cancer metastatic to the liver. A prospective randomized phase II trial of hepatic artery embolization versus hepatic artery chemoembolization was conducted to evaluate the response rates and toxicities of these therapies in the second-line setting. Patients were required to have biopsy-proven adenocarcinoma of the colon or rectum metastatic to the liver, with the liver as the sole or predominant site of metastatic disease. All patients had measurable disease and had failed at least one prior systemic chemotherapy treatment for metastatic disease. Patients were randomized to receive either embolization therapy with polyvinyl alcohol foam (Ivalon) administered as a single agent or chemoembolization using polyvinyl alcohol foam mixed with 750 mg/m2 of 5-fluorouracil and 9 million units of interferon. Drugs and embolic material were administered via the hepatic artery as a slurry with polyvinyl alcohol foam. Fifty eligible patients were enrolled. There were 24 patients in the chemoembolization arm and 26 in the embolization arm. Sixty-four percent of patients in both treatment arms had the liver as the sole metastatic site. The most common National Cancer Institute common toxicity criteria grade 3/4 toxicities were diarrhea (17%) and hepatic toxicity (8%). There was 1 (4%) treatment-related mortality due to a hepatic abscess. Four patients (15.4%) treated with embolization had a partial response (PR), and 5 patients (20.8%) treated with chemoembolization had a PR. The median survival for all patients was 11 months (95% confidence interval [CI], 8-15 months). Survival in patients with extrahepatic disease was 8 months (95% CI, 6-10 months). Survival in patients with liver-only metastases was 15 months (95% CI, 10-17 months). Embolization of the liver as second-line therapy in patients with liver-predominant metastases is safe and effective. Median survivals are comparable to other second-line therapies
Clin Colorectal Cancer 2002 Nov
PMID:Randomized phase II trial of embolization therapy versus chemoembolization therapy in previously treated patients with colorectal carcinoma metastatic to the liver. 1248 35

Colorectal cancer (CRC) is one of the most common malignant tumors in adults. Twenty-five percent of patients are not amenable to surgical resection because they have locally advanced or metastatic disease. For these patients, median survival time is between 4 and 13 months, and chemotherapy is used mainly with palliative intent. We conducted this study to evaluate potential prognostic factors for time to progression and survival. A retrospective review of 91 patients with metastatic CRC treated with bolus 5-fluorouracil-based chemotherapy (Mayo Clinic schedule) was performed. Univariate and multivariate analyses of clinical prognostic factors were carried out. Median follow-up time was 53 months (range, 17-107 months). Median time to disease progression was 9.6 months, and median survival time was 15.4 months. Actuarial 5-year survival was 17%. In the univariate analyses, factors predictive of time to progression were visceral metastases, elevated alkaline phosphatase (AP) levels, performance status (PS), and elevated carcinoembryonic antigen (CEA) and CA 19-9 levels. Multivariate analyses confirmed the independent prognostic value of PS and AP levels. In the univariate analyses for survival, significant prognostic factors were visceral metastases, hypoalbuminemia, elevated lactate dehydrogenase levels, elevated AP levels, PS, and elevated CEA and CA 19-9 levels. In the multivariate analyses, only PS, elevated CEA and CA 19-9 levels, and liver involvement retained prognostic significance. This study confirms the prognostic value of PS for both time to progression and survival. AP levels are significantly related to time to progression. Additional factors influencing survival time are elevated tumor marker levels and the existence of liver metastases.
Clin Colorectal Cancer 2003 Feb
PMID:Analysis of clinical prognostic factors for survival and time to progression in patients with metastatic colorectal cancer treated with 5-fluorouracil-based chemotherapy. 1262 Jan 43

Colorectal Cancer (CRC) is the most frequent digestive cancer in France and a major public health problem. The benefits of adjuvant chemotherapy after curative resection of Stage III CRC has been clearly demonstrated. For metastatic CRC, palliative chemotherapy allows an improvement in survival duration and quality of life compared with symptomatic treatment. 5-FU/Leucovorin chemotherapy (Mayo Clinic protocol and LV5FU2) is the standard adjuvant therapy. The addition of irinotecan (FOLFIRI) or oxyplatin (FOLFOX) to this regimen may improve response in palliative situations. These two regimens have shown their superiority to 5FU/Leucovorin in both tumor response and survival. A good objective response to palliative chemotherapy may allow for a secondary resection of hepatic metastases as part of a multidisciplinary approach. Current studies aim to define: 1) optimal treatment strategies (which drug protocols? in what order?) as they apply to tumor spread, drug toxicity profiles, the general state of the patient, and the desired therapeutic effect; 2) evaluation of new drugs and novel therapeutic approaches. Despite notable progress, the prognosis still remains grim with a survival of only 40% at 5 years. Any improvement in results will require not only an improvement in chemotherapy but also an improvement in methods of early diagnosis (systematic mass screening) which would permit the diagnosis of CRC at earlier stages where curative resection is feasible.
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PMID:[Chemotherapy for colorectal cancers]. 1270 55

Hepatic colorectal metastases present a challenging problem in patients with recurrent colorectal cancer. Twenty percent of patients with recurrence will have liver metastases as a component of their disease, and only 10% of these patients will have isolated liver metastases that are resectable. Although systemic chemotherapy alone has not proven efficacious in the treatment of liver metastases, a number of options exist in managing these lesions. For those that are resectable, surgery remains the optimal treatment, with an expected 5-year survival rate of 33%-39% based on several large series. Hepatic artery chemotherapy is another adjunct treatment in patients undergoing resection and may further improve survival. This benefit may be even more pronounced when combined with systemic chemotherapy. Newer-generation agents are likely to further improve results. More recently, new therapeutic modalities have been used to treat unresectable lesions. These include hepatic artery chemotherapy and ablative techniques such as radiofrequency ablation and cryoablation. This article will highlight the data regarding hepatic resection for colorectal metastases, describe the rationale for and efficacy of hepatic arterial chemotherapy in the postoperative adjuvant setting and in unresectable liver disease, and review the current literature describing ablative techniques in the treatment of liver metastases.
Clin Colorectal Cancer 2003 May
PMID:Locoregional strategies for colorectal hepatic metastases. 1277 91

OBJECTIVE: To determine the factors affecting survival following palliative large bowel resection for colorectal adenocarcinoma. PATIENTS AND METHOD: From the Colorectal Cancer Database of a single institution patients who had a palliative resection of a colorectal cancer from 1980 to 1993 inclusive were identified. Survival curves were constructed using the Kaplan-Meier method. Criteria studied were sex, age at operation, site of tumour, T, N and M status, tumour differentiation, involvement of tumour margins, tumour fixity and the presence or absence of peritoneal, liver or distant metastases. Multivariate analysis of factors was conducted using Cox proportional hazards analysis. RESULTS: Three hundred and seventy-seven patients (232 men, 145 women, median age 64 years) fitted the above criteria. Operative mortality was 5.6%. Crude 6 month survival rate was 71.1% and median survival 10.5 months. Significant factors affecting survival on univariate analysis were - Age (<75 vs. >75 years) (P=0.019); T status (T1/T2 vs. T3/T4) (P=0.039); nodal status (N0 vs. N1/N2) (P=0.0059); distant metastases (P=0.039) or liver metastases (P=0.0058); tumour differentiation (poor vs. moderate/well differentiated) (P < 0.001); involved tumour margins (P < 0.001). Multivariate analysis found the following factors significant: age (P=0.02), liver metastases (P=0.05), distant metastases (P=0.044), T status (P=0.042), nodal status (P=0.0063), tumour differentiation (P < 0.001) and involvement of tumour margins (P < 0.001). CONCLUSIONS: The data suggest that palliative resection of advanced colorectal carcinoma should be considered carefully in patients with advanced age, where distant metastases are present and in cases when primary tumours can not be completely resected. For the remaining patients, palliative resection may be accomplished with acceptable operative mortality and postoperative survival.
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PMID:Factors affecting survival after palliative resection of colorectal carcinoma. 1278 Jun 52

Although the role of prophylactic oophorectomy is currently under debate and not well defined, it is of increasing and considerable relevance, especially in premenopausal women, particularly those with identifiable hereditary cancer syndromes. Patients with colorectal cancer with ovarian metastases are often symptomatic, require surgery, and have poor survival. Prophylactic oophorectomy abolishes the increased risk of primary ovarian cancer in these patients, resects synchronous metastases, and prevents development of metachronous ovarian metastases. Prophylactic oophorectomy trials, mostly conducted in postmenopausal women, have not shown survival advantage. In patients with ovarian metastases of colorectal cancer, maximal cytoreductive surgery followed by adjuvant therapy employing newer chemotherapeutic agents, whole abdominal irradiation with chemosensitization, or hyperthermic intraperitoneal chemotherapy may improve outcomes in selected patients.
Clin Colorectal Cancer 2004 Feb
PMID:Ovarian neoplasms in patients with colorectal cancer: understanding the role of prophylactic oophorectomy. 1502 94


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