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At least 109 records · Page 6Linked to original sources
PubMed2001

Irinotecan and oxaliplatin: an overview of the novel chemotherapeutic options for the treatment of advanced colorectal cancer.

Colorectal cancer is one of the most frequent malignancies in humans and an important cause of cancer death. Metastatic colorectal cancer remains incurable with available systemic therapeutic options. The most active cytotoxic drug against this malignancy, the antimetabolite 5-fluorouracil, was developed more than forty years ago, and as a single agent produces responses in only 10 to 15% of patients which in general last less than one year. Efforts to ameliorate these poor results resulted in the 5-fluorouracil/leucovorin combination, which enhances response rates about two-fold, without, however, significantly improving survival rates. The recent emergence of a handful of new 5-fluorouracil analogues and folate antagonists, as well as the topoisomerase I inhibitor irinotecan, and the third-generation platinum compound oxaliplatin, is likely to alter this gloomy scenario. These agents are at least as effective as 5-fluorouracil in patients with advanced colorectal carcinoma, both untreated and previously treated with 5-fluorouracil-based regimens. This has led to the approval of irinotecan as second-line treatment for 5-fluorouracil-refractory disease, while the use of oxaliplatin has been suggested for patients having a defective 5-fluorouracil catabolism. Recently, FDA approved the combination of irinotecan with 5-fluorouracil and leucovorin for first-line treatment of advanced colon cancer. Based on the synergistic preclinical antitumor effects of some of these agents, their meaningful single-agent activity, distinct mechanisms of cytotoxicity and resistance, and only partially overlapping toxicity profiles, effective combination regimens are now being developed, which are likely to lead to a new, more hopeful era for patients suffering from advanced colorectal carcinoma.

Antimetabolites, Antineoplastic↗
PubMed1999

COX-2 inhibitors: a potential target for drug therapy in the management of colorectal cancer.

Colorectal cancer is currently the third most common cancer in Malaysia. Elevated expression of COX-2, an induced cyclooxygenase isoenzyme, has been seen in colonic adenomas and colorectal carcinoma. There is evidence that inhibition of this COX-2 can decrease the risk of colorectal cancer. Selective COX-2 inhibitors may have a role in reducing the risk of colorectal cancer in high-risk individuals.

Animals↗
PubMed1988

[Clinical effect of postoperative adjuvant immunochemotherapy with the FT-207 suppository and PSK in colorectal cancer patients. Colorectal Cancer Chemotherapy Group in Hokuriku].

For a period of about three years from September 1980, a randomized controlled study was performed on colo-rectal cancer patients who had undergone an absolute curative operation. After operation and administration of 30 mg of Mitomycin (20 mg on the day and 10 mg on the day following the operation), all patients were randomly divided into two groups which received the treatments as follows; Group A, 750 mg x 2/day of FT-207 suppositories, was administered for one year from the 2 nd week after operation; Group B was given FT-207 3.0 g/day of PSK orally for one year. Group A included 71 patients, of whom 46 had colon cancer and 25 had rectal cancer. Group B included 53 patients, of whom 30 patients had colon cancer and 23 had rectal cancer. There was no difference between the two groups in terms of patients' background factors. In regard to the 5-year survival rates of these patients by means of the Kaplan-Meier Method, Group A and B showed 80.8% and 91.4%, respectively, but no significant difference was observed. In the colon cancer patients, 5-year survival rates were 88.6% and 93.0% in Group A and B, and in the rectal cancer patients, they were 68.0% and 87.5% in Group A and B, respectively. The survival rate of Group B was always slightly higher than that of Group B in all analyses, in which we considered such factors as degree of progression, depth of cancer invasion of the wall, lymphnode metastases and vascular invasion. There were no differences between both groups in the patterns and times of recognition of the recurrences, but the number of cases evidencing recurrences within 2 years tended to be smaller in Group B. Thus, it was suggested that PSK was effective for prolongation of the survival period in colo-rectal cancer patients after absolute curative operation.

Administration, Oral↗
PubMedDate not supplied

Recent advances in systemic chemotherapy of metastatic colorectal cancer.

Colorectal cancer is the second most common cancer in the Western world. Nearly 6 out of 10 patients with colorectal cancer have or will have metastasis, and among patients with advanced disease, the liver is the most common site involved (in up to 70% of patients). Chemotherapy of advanced CRC was long considered as ineffective. Recently, however, chemotherapy has made great strides: a number of successful regimens have been reported especially since 1990. The first randomized trials showing a significant extension of survival in patients treated by chemotherapy as compared to those receiving only supportive care were published in 1992 and 1993. This article provides an up-to-date overview of palliative chemotherapy for metastatic colorectal cancer: tumor reduction is two times greater when 5FU is administered in combination with folinic acid or with Methotrexate than when it is administered alone. According to some studies, these combinations may also significantly improve the duration and quality of survival. Two recent controlled studies comparing systemic chemotherapy with supportive care showed a significant improvement in the duration of survival and a study in asymptomatic patients indicated a significant extension of the duration of the symptom-free period. Hepatic intra-arterial chemotherapy significantly prolongs survival but toxicity is high. Further clinical testing is needed to evaluate new agents, improve tolerance to treatment, and evaluate chemotherapy as a bridge to surgery for patients with initially inoperable metastasis.

Antineoplastic Agents↗
PubMed1989

Inherited susceptibility to colorectal cancer.

Colorectal cancer and its potential precursor, adenomatous polyps, tend to aggregate in families, but it is not clear why. Heritability is established for only rare colorectal cancers, some prominently involving polyposis. Preliminary studies suggest, however, that susceptibility to the common colorectal cancer precursors, "sporadic" adenomatous polyps, is also inherited.

Adenoma↗
PubMed1981

Screening for colorectal cancer.

Colorectal cancer remains a major cause of mortality in the United States. Of all persons diagnosed with this tumor, less than 50 percent survive five years. Useful preventive measures have not been established. Screening programs, however, offer the prospect of detecting cancers early in their course, when the prognosis for survival is more favorable. To date, no screening test has clearly demonstrated its effectiveness in reducing mortality from colorectal cancer. Periodic rigid sigmoidoscopy and stool occult blood testing have gained many advocates, but have yet to be proved worthwhile in adequately controlled clinical trials. Uncontrolled studies indicate that both these techniques discover approximately 2 cancers per 1000 screenees. There is suggestive evidence that the cancers discovered are more likely to be localized. For the present, physicians should limit colorectal cancer screening to persons at relatively high risk: persons aged over 45 years, with a family history of bowel cancer, or with polyps. Protocols should be designed to ensure high specificity. The recommendations of the National Cancer Institute's consensus conference provide practical guidelines pending the outcome of randomized controlled trials.

Adult↗
PubMed2006

Chemoprevention of colorectal cancer.

Colorectal cancer is a major public health concern in all developed countries. Despite decades of advances in the treatment and prevention of colorectal cancer, it remains the second most common cause of cancer death. However, the optimal method for early detection remains unknown and patient compliance with screening recommendations remains poor. This has led to the development of complementary strategies, such as chemoprevention to reduce morbidity and mortality from colorectal cancer. Chemoprevention is defined as the use of specific pharmacologic or nutrient agents to prevent, reverse, or inhibit the process of carcinogenesis. This review was designed to discuss the most promising agents in colorectal chemoprevention.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Phase I/II trial of gefitinib and oxaliplatin in patients with advanced colorectal cancer.

Colorectal cancers frequently overexpress the epidermal growth factor receptor. Gefitinib (Iressa), an inhibitor of the epidermal growth factor receptor tyrosine kinase, is synergistic with oxaliplatin in preclinical colon cancer models. The authors conducted a phase I/II trial of gefitinib plus oxaliplatin in patients with previously treated metastatic colorectal cancer. In the phase I portion, 14 patients received oxaliplatin 130 mg/m2 intravenously every 21 days and gefitinib orally daily at 1 of 2 dose levels: 250 mg/day (8 patients), and 500 mg/day (6 patients). There were no objective responses. Three patients (38%) in the 250-mg cohort experienced disease stabilization for a median of 12 weeks, and 1 patient in the 500-mg cohort had stable disease for 18 weeks. Nausea/vomiting and rash were dose limiting. The randomized phase II part of the trial, in which patients were to receive oxaliplatin with or without gefitinib, was canceled due to the inactivity of single-agent gefitinib observed in the phase I portion, and emergent phase III data regarding the minimal activity of single-agent oxaliplatin. The authors conclude that the combination of gefitinib plus oxaliplatin is inactive in advanced colorectal cancer.

Adult↗
PubMed1998

Chemoprevention of colorectal cancer.

Colorectal cancer is the fourth commonest form of cancer in men with 678 000 estimated new cases per year worldwide, representing 8.9% of all new cancers. The disease is most frequent in Occidental countries and particularly so in North America, Australia, New Zealand, and parts of Europe. Prospects for colorectal cancer control are bright and a number of possible approaches could prove fruitful. Among these, pharmaceutical measures seem to be valid and logical approaches to the prevention of colorectal cancer and diminishing its impact. Such approaches could concentrate in primary prevention in at-risk subjects or be applied in altering the course of precursor or established disease. Treatments used must fulfil basic requirements of biological plausibility and safety in continued use in large numbers of subjects. Those available include vitamins and minerals, and other drugs with potential as antioxidants, immune modulators or promoters of cell differentiation or apoptosis. Of the various regimens suggested, vitamin A supplementation may even predispose to adverse outcomes, and antioxidant vitamins in general have no coherent body of evidence to support their use. N-acetylcysteine and ursodeoxycholic acid have promising characteristics but there are as yet no clinical data to support the use of the former in gut epithelial cancer, and formal dose ranging studies must be carried out before the latter is submitted to large scale trial. Folate shows promising characteristics but non-steroidal anti-inflammatory drugs and vitamin D seem the most promising agents. Both seem to reduce the incidence of disease, and to reduce growth rates and/or induce differentiation or apoptosis in gut epithelial cancer cells. Both are also well understood pharmacologically. They may be preferred to newer selective compounds in the same class until these newer compounds are confirmed as safe for widespread long term use.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

[Surgery in complicated colorectal cancer].

Colorectal cancer continues to have a serious social impact. A large proportion of patients are diagnosed at an advanced stage of the disease. Approximately one-third of patients with colorectal cancer will undergo emergency surgery for a complicated tumor, with a high risk of mortality and poorer long-term prognosis. The most frequent complications are obstruction and perforation, while massive hemorrhage is rare. The curative potential of surgery, whether urgent or elective, depends on how radical the resection is, among other factors. In the literature on the management of urgent colorectal disease, there are few references to the oncological criteria for resection. Uncertainly about the optimal treatment has led to wide variability in the treatment of this entity. The present article aims to provide a critical appraisal of the controversies surrounding the role of surgery and its impact on complicated colorectal cancer.

Colorectal Neoplasms↗
PubMed2001

New chemotherapy approaches in colorectal cancer.

Colorectal cancer is one of the leading causes of cancer deaths in the Western world, with approximately 50% of all patients dying from metastatic disease. Until recently, therapeutic options for advanced colorectal cancer were mainly confined to chemotherapy with 5-fluorouracil in various schedules, with or without biochemical modulation with leucovorin. The development of new cytotoxic drugs with substantial activity in this tumor during the past 2 years has dramatically changed treatment strategies and therapeutic goals in metastatic colorectal cancer and has introduced neoadjuvant chemotherapy followed by secondary surgery with the intent of long-term survival. Among these new drugs, oral fluoropyrimidines (tegafur/uracil and capecitabine), irinotecan, and oxaliplatin have already established themselves as part of various treatment approaches. Other novel therapeutics including agents designed to act on molecular targets already show promising activity and will become part of combination protocols with current standard chemotherapy.

Administration, Oral↗
PubMed1996

Screening for Colorectal Cancer.

Colorectal cancer is a major cause of morbidity and mortality in the United States. Early detection of the disease at an asymptomatic stage by screening holds promise for lowering the incidence of colorectal cancer deaths, yet compliance with screening guidelines is poor. Evidence in support of the use of screening techniques for colorectal cancer is accumulating, however, and screening for this disease with fecal occult blood tests and flexible sigmoidoscopy can increase the likelihood of early detection, can decrease mortality and morbidity, and can be cost effective.

Journal Article↗
PubMed1998

Advances in the treatment of metastatic colorectal cancer.

Colorectal cancer is the second leading cause of cancer-related deaths in men and women in the United States. In 1997, it is estimated that 131,200 new cases of colorectal cancer will be diagnosed and 54,900 deaths will occur due to the disease. Although the tumor is localized at the time of diagnosis and resection with curative intent is possible in approximately 75% of patients, more than a third will develop disease recurrence. Consequently, almost half of all patients with colorectal cancer will die of metastatic disease.

Journal Article↗
PubMed1987

Screening for colorectal cancer.

Colorectal cancer is a good candidate for secondary prevention strategies. It appears to have a long lead time since most, if not all, of these cancers arise from premalignant adenomas, and several screening methods are available that might detect the cancer in a very early stage. However, there is little evidence at present to show that the available methods of early detection will actually decrease the mortality from colorectal cancer of a screened population as compared to a non-screened population. Studies that might convincingly provide this evidence are still in progress. This paper critically reviews the natural history of colorectal cancer, risk factors, screening trials and treatment.

Colonic Neoplasms↗
PubMed1999

Natural history of colorectal cancer.

Colorectal cancer arises from a precursor lesion, the adenomatous polyp, which forms in a field of epithelial cell hyperproliferation and crypt dysplasia. Progression from this precursor lesion to colorectal cancer is a multistep process, accompanied by alterations in several suppressor genes that result in abnormalities of cell regulation, and has a natural history of 10-15 years. Environmental factors and inherited susceptibility play major roles in this sequence of events. As a result of familial and genetic studies, we now have a better understanding of various high-risk groups and the application of screening methods to these individuals and to people at average risk. In the future, further identification of genetically predisposed individuals and colonoscopic screening of the general population may provide new opportunities for control of colorectal cancer through secondary prevention, and a better understanding of lifestyle factors and their modification will lead to improved strategies for primary prevention.

Colonic Polyps↗
PubMed2004

Recent phase III trials of fluorouracil, irinotecan, and oxaliplatin as chemotherapy for metastatic colorectal cancer.

Colorectal cancer is a leading cause of cancer death worldwide. Recently the results of a number of well-designed clinical trials conducted across the world have led to important advances in the management of advanced colorectal cancer. These iterative studies fostered the evolution from a standard single-agent approach using fluorouracil (5-FU) to new combination regimens including capecitabine, irinotecan, and oxaliplatin in addition to 5-FU. These developments have significantly expanded the expectations of oncologists managing the disease and the options available to individuals, leading to a likelihood of extended survival compared to previous statistics. The identification of new combination chemotherapy regimens and the integration of novel targeted therapies with cytotoxic chemotherapies are areas of active clinical investigation. In this paper selected phase III studies from around the globe that tested these new chemotherapy options and led to new standards of care and better expectations for patients with advanced colorectal cancer are reviewed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Recent advances in the systemic management of colorectal cancer.

Colorectal cancer represents one of the most prevalent malignancies. There have been considerable improvements in the management of the disease in the last decade, including advances in surgery. In terms of systemic management, 5-fluorouracil, usually with leucovorin, has remained the mainstay of chemotherapy for colorectal cancer in both the adjuvant and metastatic settings. In the late 1990s, irinotecan and oxaliplatin reached the clinical arena, and the introduction of these agents has led to significant improvements in outcomes. More recently, several biopharmaceuticals, including the monoclonal antibodies bevacuzimab and cetuximab, have shown promise in clinical studies. These novel agents are now being incorporated into treatment schedules for colorectal cancer. This review assesses recent improvements in the systemic management of large bowel cancer and highlights future challenges.

Antibodies, Monoclonal↗
PubMed2006

Capecitabine: a new adjuvant option for colorectal cancer.

Colorectal cancer continues to pose a major public health threat in the United States. Without postsurgical adjuvant therapy, approximately 50% of patients will have recurrent disease and die within five years. Since 1990, five new chemotherapy agents have been added to the therapeutic armamentarium for management of colorectal cancer, and agents traditionally used to treat metastatic and advanced disease increasingly are being applied in the adjuvant setting. One such treatment, capecitabine, offers patients the benefit of oral dosing and permits at-home self-management. A phase III randomized trial, Xeloda in Adjuvant Colorectal Cancer Treatment, demonstrated that treatment with single-agent capecitabine was equivalent to bolus 5-fluorouracil with leucovorin with respect to disease-free survival and overall survival, with significantly less diarrhea, stomatitis, neutropenia, nausea and vomiting, and alopecia. This article reviews the findings and discusses how oncology nurses can help provide effective education and monitoring for patients using oral treatment in the adjuvant setting.

Administration, Oral↗