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)

Efforts to improve the length and quality of life, as well as to expand treatment options, for patients with metastatic colorectal cancer have only recently become more successful. With maximization of dose and schedule schemes for fluoropyrimidine therapy, new drugs such as irinotecan (CPT-11, Camptosar) and oxaliplatin have also become part of the standard therapy for patients. Combination chemotherapy has been established to have superior response rates and progression-free survival and--in some instances, for fluorouracil and irinotecan combinations--improved overall survival compared to fluorouracil alone. There is still much to be learned about the optimal management of patients with colorectal cancer, including the role of second- and third-line chemotherapy in the overall survival outcome, and the role of salvage therapy in patients with limited metastatic disease. Most importantly, the development of a biological marker of prognosis and response should help to select appropriate chemotherapy programs for patients on a rational and individual basis, not only in the setting of metastatic disease, but also in the adjuvant population.
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PMID:Update on chemotherapy for advanced colorectal cancer. 1130 34

Colorectal carcinoma is one of the most common malignancies in the western world, and although fluorouracil (5-FU) has been used in its treatment for almost 40 years, new agents with significant activity have been introduced recently. Irinotecan (CPT-11, Camptosar), a topoisomerase I inhibitor, administered at 300 to 350 mg/m2 every 3 weeks is significantly more active than continuous-infusion 5-FU in patients who have experienced disease progression after conventional therapy with 5-FU. In comparison to best supportive care, irinotecan improves survival and preserves quality of life despite treatment-related toxicity. Moreover, the combination of irinotecan and 5-FU has been explored in a number of different schedules. In previously untreated patients, overall response rates are high. Irinotecan can also be combined with mitomycin (mitomycin-C [Mutamycin]), oxaliplatin, or raltitrexed (Tomudex). Oxaliplatin is a new-generation platinum compound that has demonstrated activity against colorectal carcinoma in preclinical trials. It has been evaluated as a single agent against advanced colorectal carcinoma in the salvage setting and also in combination with 5-FU as initial therapy for metastatic disease (where it shows significant activity). The toxicity profile of oxaliplatin (chiefly characterized by neurotoxicity) differs from that of irinotecan (primarily producing diarrhea) and the potential, therefore, exists for combining these agents or for exploiting their possible synergy with 5-FU. The introduction of these two new active agents of different pharmacologic classes promises to enable significant improvements in the treatment of patients with colorectal carcinoma.
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PMID:The role of irinotecan and oxaliplatin in the treatment of advanced colorectal cancer. 1134 31

Traditionally, the role of chemotherapy in the treatment of squamous carcinoma of the head and neck has been confined to patients with recurrent or metastatic disease who are deemed incurable with surgery or radiation therapy. Over the past decade, however, the role of chemotherapy has changed dramatically. The use of primary combined chemoradiation to preserve function or to enhance survival in patients with unresectable disease has become a standard approach. As the use of chemotherapy in squamous carcinoma of the head and neck has expanded, investigators have been interested in identifying new active agents. Topoisomerase I inhibitors, a new class of drugs, have been found to be active in a number of solid and hematologic malignancies. Three topoisomerase I inhibitors have been investigated in the treatment of metastatic or recurrent squamous carcinoma of the head and neck: 9-aminocamptothecin (9-AC), topotecan (Hycamtin), and irinotecan (CPT-11, Camptosar). Neither 9-AC nor topotecan has demonstrated clinically significant activity in the treatment of metastatic or recurrent squamous carcinoma of the head and neck. In contrast, irinotecan has demonstrated a modest overall response rate of 21.2% (95% confidence interval [CI] = 9%-38.9%), with a median survival of 214 days and a 1-year survival rate of 30.2%. The response and toxicity appear to be dose dependent. Further investigation of irinotecan in combination with other active agents and radiotherapy is warranted.
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PMID:Topoisomerase I inhibitors in the treatment of head and neck cancer. 1149 32

Liver is the common site for metastases from colorectal cancer. The 5-year overall survival rate of patients following radical operations is 25%. Surgery can be carried out in only 10-15% of the patients, yet it remains the potential curative treatment for resectable lesions. For the unresectable cancers, only chemotherapy is recommended. New drugs such as Irinotecan prolongs the overall survival of patients affected by advanced disease. In patients with unresectable metastases at diagnosis, pre-surgical treatment with Oxaliplatin leads to reduction of the lesions, allowing resection in 16% of cases. Chemotherapy may be delivered directly into the liver via the hepatic artery. No, clinical trials, to date, have shown convincing survival results in patients treated with this procedure. Combined hepatic artery and systemic treatment may provide a new strategy as adjuvant therapy for patients undergoing resections.
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PMID:Treatment of liver metastases from colorectal cancer: what is the best approach today? 1152 58

Colorectal cancer is the second leading cause of cancer death and it is clear that patients with metastatic disease have better quality of life and survival when given treatment. Despite four decades of experience of treating patients with fluorouracil, there remains considerable controversy about the optimum dose and scheduling, as well as biomodulation with leucovorin and methotrexate. However, irrespective of the dose and schedule, overall survival times are poor--about 1 year. Disappointingly, oral agents with similar mechanisms to fluorouracil do not improve survival rates in comparison with fluorouracil and leucovorin treatment. Irinotecan and oxaliplatin are newer agents that have improved the response rates for patients with metastatic disease when they are added to flurouracil and leucovorin. The combination of irinotecan, fluorouracil, and leucovorin has also improved overall survival. These are small advances in the fight against colorectal cancer, and further drug development is necessary.
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PMID:New therapies, new directions: advances in the systemic treatment of metastatic colorectal cancer. 1190 84

Despite advances in screening procedures and the use of adjuvant therapy, approximately 50% of patients with colorectal cancer eventually will develop metastatic disease. Long-term disease-free survival can be achieved in 25% to 40% of selected patients who undergo resection of liver or lung metastases. For all other patients, treatment is palliative. For decades, 5-fluorouracil was the only available drug for colorectal cancer; hence, numerous trials were performed that used various administration schedules and modulating agents to improve therapeutic efficacy. The addition of leucovorin to 5-FU improves response but not survival. Infusion schedules alter the toxicity profile but have a negligible impact on survival. Irinotecan was the first new drug to demonstrate activity in colorectal cancer. It was used initially in the second-line setting, where it was shown to improve quality of life and survival over best supportive care or infusional 5-FU. Recently, irinotecan has been incorporated into the front-line treatment of metastatic colorectal cancer in combination with 5-FU and leucovorin; this combination improves survival by approximately 3 months. Careful patient selection and adherence to strict dose adjustments are essential to prevent significant toxicity when patients are treated on this regimen. The oral fluoropyrimidine capecitabine recently has been approved for the front-line treatment of patients with colorectal cancer who are not appropriate candidates for combination therapy. Oxaliplatin, a novel DACH (diaminocyclohexane) platinum with definite activity in colorectal cancer, is approved for this disease in Europe and is undergoing phase III clinical trials in the United States. Other drugs with potential activity in colorectal cancer include raltitrexed, pemetrexed disodium, and the epothilone analog BMS-247550 (Bristol-Myers Squibb, New York, NY). Novel cytostatics with promising activity in colorectal cancer are being evaluated in clinical trials, including epidermal growth factor receptor inhibitors, such as IMC-C225 (Imclone Systems, New York, NY) and ZD1839 (AstraZeneca, London, UK), angiogenesis inhibitors such as bevacizumab and SU5416 (Sugen, San Francisco, CA), and vaccines such as CEAVac (Titan Pharmaceuticals, San Francisco, CA). For those patients whose disease is localized to the liver, there also is an emerging role for local therapies, including cryosurgery, radiofrequency ablation, and hepatic artery infusional chemotherapy, and resection. The emergence of these new drugs and new interventional modalities has allowed physicians who treat colorectal cancer to move beyond 5-FU.
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PMID:Metastatic colorectal cancer. 1205 92

Preoperative or postoperative pelvic radiation plus concurrent fluorouracil-based chemotherapy is standard adjuvant treatment for patients with T3 and/or N1/2 rectal cancer. Newer chemotherapeutic regimens have been developed for the treatment of patients with metastatic disease. Irinotecan (CPT-11, Camptosar)-based regimens have improved survival in patients with metastatic disease and are being actively investigated in combination with pelvic radiation therapy for patients with rectal cancer.
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PMID:Combined-modality therapy for rectal cancer using irinotecan. 1210 5

Irinotecan and mitomycin (Mutamycin) possess significant single-agent activity against several tumor types, and mitomycin activates topoisomerase I, the cellular target of irinotecan. We conducted a phase I dose-escalation study of irinotecan and mitomycin in 37 evaluable patients with solid tumors. Antitumor responses included 2 complete responses, 5 partial responses, 10 minor responses, and a CA 19-9 tumor marker response. Responders included 14 patients previously treated with chemotherapy for metastatic disease. No pharmacokinetic interaction between mitomycin and irinotecan was apparent when these agents were given 24 hours apart. Responders (complete and partial responses) demonstrated the largest topoisomerase I induction 24 hours following mitomycin infusion. In addition, since maximum topoisomerase I up-regulation was reached 24 hours after administration of mitomycin, a delay in the administration of irinotecan after mitomycin appeared justified. Based on these encouraging phase I data, phase II clinical trials in breast and esophageal/gastroesophageal junction adenocarcinomas at the recommended doses and schedule are under way.
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PMID:Mitomycin as a modulator of irinotecan anticancer activity. 1219 29

We investigated the activity of irinotecan given with a more convenient modified bimonthly de Gramont regimen of bolus and infusional 5-fluorouracil [IrMdG] in advanced or metastatic colorectal cancer in the first and second line setting. Irinotecan 180 mg m(-2) was infused over 90 min. L-folinic acid 175 mg or d,l folinic acid 350 mg was given over 2 h followed by a bolus of 5-fluorouracil (400 mg m(-2)) and a 46 h continuous infusion of 5-fluorouracil (2.4-2.8 g m(-2)). Forty-six previously untreated patients (Group A) and 36 who had received 5-fluorouracil for metastatic disease (Group B) were recruited. Seventy-eight patients were evaluable for response. A partial response was seen in 13 out of 43 (30% [95%CI 28.1-31.9%]) in Group A and 8/35 (23% [95% CI 17.9-28.1%]) in Group B. 40% (95%CI 38.1-41.9%) of Group A and 26% (95% CI 20.9-31.1%) of Group B patients achieved disease stabilisation. The median progression free survival from the start of this treatment was 7 months (95% CI 4.4-9.6 months) in Group A and 5 months (95% CI 2.8-7.2 months) in Group B. Median overall survival was 14 months (95% CI 9.0-18.9) in Group A and 11 months (95% CI 5.9-16.1) in Group B. Grade 3-4 toxicity in both treatment groups were similar; leucopenia 17% and diarrhoea 7-8%. Grade 3-4 mucositis was not seen and severe alopecia affected only three patients. IrMdG is an active and well-tolerated regimen for both the first and second line treatment of advanced colorectal cancer.
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PMID:Phase II study of irinotecan with bolus and high dose infusional 5-FU and folinic acid (modified de Gramont) for first or second line treatment of advanced or metastatic colorectal cancer. 1243 8

Hepatoblastoma is the most common liver tumor diagnosed in children. Children with persistently unresectable disease, metastatic disease at presentation, recurrent disease, or slowly declining alpha-fetoprotein levels are at high risk for recurrence, exhibit an extremely poor prognosis, and are in desperate need of novel therapeutic agents and strategies. Four high-risk patients were treated. One patient with a local recurrence was treated with irinotecan followed by orthotopic liver transplant. Three patients were treated with tandem high-dose chemotherapy (HDT) with autologous stem cell rescue (two with primary metastatic disease and one with recurrent disease). All three of the patients treated with HDT had relapse (two of them subsequently received irinotecan); the remaining patient underwent surgical resection of a solitary recurrent pulmonary metastasis. Irinotecan demonstrated significant antitumor effects in all three treated patients and was well tolerated. None of the three patients treated with HDT remained disease-free, although the patient who underwent surgical resection of a solitary recurrent pulmonary metastasis remains disease-free 6 years from diagnosis. Further exploration of the use of irinotecan is warranted in high-risk patients with hepatoblastoma.
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PMID:Novel therapeutic approaches in the treatment of children with hepatoblastoma. 1246 18


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