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)

Esophageal cancer is uncommon, but its incidence is rapidly increasing in the Western countries because of the high incidence of the cardia esophageal adenocarcinoma. Notwithstanding the encouraging results achieved with surgical procedures, esophageal carcinoma has a poor prognosis with 5-year survival in 10% of cases without differences between both squamous and adenocarcinoma histologies. Almost 50% of esophageal cancer patients have unresectable disease at presentation; in the past years combined modality treatments, using chemotherapy and/or radiotherapy with or without surgery, have been evaluated to reduce the risk of local and/or distant recurrences. Ongoing regimens with new agents (Taxanes, Vinorelbine, Irinotecan), in association or not with platinum compounds, show good antitumor efficacy and tolerability, even in the metastatic disease. Preoperative strategies with radiation only did not give any advantage compared to surgery alone, instead, controversial results were obtained, with a minimal advantage, using chemotherapy. Combined chemotherapy and radiation, in suitable candidates for resection has shown an improvement of complete pathological responses, in both the histologies, but with superior toxicities when compared to chemotherapy or radiation therapy alone. Postoperative adjuvant therapies as radiation, chemotherapy or both, have not led to a marked improvement in overall survival and should be performed only in clinical trials. The use of chemoradiotherapy showed a clear advantage versus radiotherapy alone and in many cases equivalent to regimens plus surgery even if control studies haven't been performed. Clinical trials with novel biologic agents, in combination to chemotherapy or alone, against cell growth arrest, neoagiongenesis and tumor metastasis invasion process are currently under evaluation. In the coming years new markers as antigen Ki-67 determination, p53 mutation or high levels activity of thymidylate synthase and novel staging techniques as PET could be precious to identify the better treatment for each patient.
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PMID:[New strategies in the treatment of esophageal cancer]. 1259 16

The limited effectiveness of chemotherapy in esophageal cancer used to palliate metastatic disease or to combine with radiotherapy in locally advanced disease has prompted the evaluation of new systemic agents. Irinotecan (CPT-11, Camptosar) has shown promising activity in a number of gastrointestinal cancers, including esophageal cancer. The phase II evaluation of the combination of weekly irinotecan and cisplatin has shown encouraging response rates exceeding 30% to 50% in esophageal and gastric cancer. Novel regimens include the combination of irinotecan with mitomycin (Mutamycin), the taxanes docetaxel (Taxotere) and paclitaxel, and continuous infusion fluorouracil (5-FU). Irinotecan is an active radiosensitizer, and trials have evaluated the combination of irinotecan with concurrent radiotherapy. We completed a phase I trial combining weekly irinotecan, cisplatin, and concurrent radiotherapy in locally advanced esophageal cancer. Minimal toxicity has been observed, with no grade 3/4 esophagitis or diarrhea, and hematologic toxicity was also surprisingly minimal. Full doses of weekly irinotecan (65 mg/m2) and cisplatin (30 mg/m2) could be combined safely with concurrent radiotherapy, with a significant rate of pathologic complete response. Phase II evaluation of this chemoradiotherapy regimen as preoperative therapy is planned at single institutions and at the cooperative group level in the United States. Further phase I and II investigation of combined irinotecan, cisplatin, and concurrent radiation is ongoing with the addition of targeted agents, including celecoxib (Celebrex), cetuximab (Erbitux), and bevacizumab (Avastin). Alternative combinations of irinotecan with radiotherapy, including the addition of docetaxel and continuous infusion 5-FU, are also undergoing phase I and II evaluation.
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PMID:Irinotecan in esophageal cancer. 1456 46

Small bowel adenocarcinoma (SBA) is a relatively rare disease. Because of its rarity the role of chemotherapy either as adjuvant or for advanced disease has not been clearly defined. Therefore any information, including case reports, is warranted. We report on three patients with adenocarcinoma of the jejunum and ileum. Two patients with positive lymph nodes received postoperative adjuvant chemotherapy with 5-fluorouracil-folinic acid (5FU-FA) for 12 months but they developed metastatic disease 3 and 8 months later, respectively. The third patient was initially treated with the same agents but for metastatic disease. All patients were subsequently treated for tumor recurrence with irinotecan 350 mg/m2 i.v. every 3 weeks as salvage chemotherapy supported by Granulocyte Colony Stimulating Factor (GCSF) for 5 days. Two patients achieved a minor response and had a dramatic improvement of their symptoms. Their survival times after irinotecan administration were 14 and 6 months with an overall survival after primary diagnosis of 29 and 27 months, respectively. The third patient who had a tumor refractory to 5FU-FA progressed also on irinotecan and had an 8-month overall survival. Although conclusions cannot be drawn regarding the role of adjuvant chemotherapy in SBA, it seems reasonable to extrapolate from large bowel carcinoma experience. Irinotecan seems to have some degree of activity in the treatment of SBA but further studies are warranted.
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PMID:Irinotecan as salvage chemotherapy for advanced small bowel adenocarcinoma: a series of three patients. 1459 44

More than one third of all non-small-cell lung cancer (NSCLC) patients present with advanced stage IV disease with metastases or with stage IIIB disease with a malignant pleural or pericardial effusion. The prognosis for these patients remains poor despite some improvement in survival produced by 2-drug chemotherapy combinations. With the best 2-drug combinations, the expected median survival is 8-9 months and > 80% of patients die within 2 years of diagnosis. The overall response rate to the best combination is < 40% and the complete response rate is only 1%. Clearly, superior therapies are needed. The topoisomerase I inhibitors have been developed because the topoisomerase I enzyme plays a critical role in the DNA repair process. Irinotecan is a topoisomerase I inhibitor developed during the 1990s. It was initially approved in the United States for the treatment of colorectal cancer. In early trials, considerable activity was seen in both small-cell lung cancer and NSCLC. These observations led to combination studies with cisplatin. Cisplatin-based therapy had become a standard approach in both stage IV disease and in combination with chest radiotherapy in stage IIIB disease because metaanalyses of randomized trials showed that cisplatin-based therapy significantly improved survival. Randomized trials also showed that cisplatin-based therapy improved symptoms in the majority of patients and improved quality of life. In early combination studies, the irinotecan/cisplatin combination produced responses in an average of 40% of patients and produced median survival times that averaged about 10 months. In randomized trials comparing irinotecan/cisplatin to vindesine/cisplatin, the irinotecan/cisplatin combination was slightly better than irinotecan alone and vindesine/cisplatin. These encouraging results led to ongoing randomized trials comparing the 2-drug combination of irinotecan/cisplatin to other 2-drug combinations. Irinotecan has also been combined safely and effectively with carboplatin. The 2-drug combination of irinotecan/carboplatin produced results similar to those achieved with irinotecan/cisplatin. Irinotecan has also been incorporated into 3-drug combinations such as irinotecan/carboplatin/paclitaxel with encouraging results. A randomized trial comparing docetaxel/irinotecan to docetaxel/cisplatin showed similar results. Randomized trials comparing the 3-drug combination to a 2-drug combination are in progress. The irinotecan/cisplatin combination has considerable activity in the second-line setting. Randomized trials comparing this combination to docetaxel are needed. Irinotecan is an active agent in the first- and second- line therapy of NSCLC.
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PMID:The role of irinotecan combined with Cisplatin or Carboplatin in the treatment of advanced non-small-cell lung cancer. 1465 34

The prognosis for non-small-cell lung cancer (NSCLC) patients remains poor, with a high percentage of patients presenting with advanced disease and metastases. Thus, the therapeutic goal is to provide optimal local control and to eradicate any metastases. The advent of novel therapies has provided new hope in the treatment of this disease. Irinotecan, a topoisomerase I inhibitor, is active in both chemotherapy-naive and previously treated NSCLC patients. In addition, its ability to act as a radiosensitizer makes it a promising candidate for use in combined modality therapy. Encouraging response rates have been achieved in multiple trials using irinotecan alone or in combination with cisplatin, carboplatin, docetaxel, and/or radiotherapy. Further phase II and III studies should clarify the benefit of combined modality therapy as well as the optimal way to integrate radiotherapy into irinotecan regimens.
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PMID:Irinotecan Combined with Radiation Therapy for Patients with Stage III Non-Small-Cell Lung Cancer: Current Trials. 1465 37

Colorectal cancer remains one of the major causes of cancer death worldwide, but the past few years have witnessed the development of a number of new, effective treatment options, which have led to considerable improvement in the survival rate for patients suffering from this common cancer. The advent of agents such as capecitabine (Xeloda), irinotecan (Camptosar), and oxaliplatin (Eloxatin), and newer molecular targeted agents such as cetuximab (Erbitux) and bevacizumab (Avastin) brought innovation to the treatment of colorectal cancer. Oncologists are no longer restricted to using fluorouracil and its variations as the only active treatment, and the number of patients who are able to live longer continues to increase. Patients presenting with stage III cancer can expect a greater chance for cure, and those presenting with metastatic disease can expect a median survival approaching 2 years.
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PMID:Progress in the development of novel treatments for colorectal cancer. 1521 91

Colorectal cancer is the second most common cause of cancer-related death in the United States. Approximately 30% to 40% of patients with colorectal cancer have locoregionally advanced or metastatic disease on presentation and cannot be cured with surgical therapy. After many years without significant change, systemic therapy for colorectal cancer is rapidly evolving. The past decade has seen the introduction of new chemotherapeutic agents such as irinotecan (Camptosar), oxaliplatin (Eloxatin) and the oral 5-FU prodrug capecitabine (Xeloda). Combination studies of these new agents with the standard 5-FU/leucovorin have extended median survival in patients with advanced colorectal cancer for up to 21 months. In addition, targeted agents with activity in colorectal cancer have emerged and are promising. This article reviews the current treatment recommendations for patients who present with advanced colorectal cancer. Survival in patients with advanced colorectal cancer is on a positive trajectory. The hope that some patients with advanced disease will be long-term survivors (even without surgery) appears to be within the range of possibility.
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PMID:Current strategies in previously untreated advanced colorectal cancer. 1521 92

Esophageal cancer is a rare but highly virulent malignancy in the United States, and adenocarcinoma of the esophagus has had the most rapid rate of increase of any solid tumor malignancy. Systemic metastatic disease is present in 50% of patients at diagnosis. In the remaining 50% presenting with local regional disease, systemic metastatic disease will develop in the vast majority of these patients. The limited efficacy and toxicity of conventional fluorouracil (5-FU)/cisplatin-based chemotherapy has prompted the evaluation of newer agents. Irinotecan (Camptosar) has shown promising single-agent activity in a number of gastrointestinal cancers, including colorectal, pancreatic, and esophagogastric cancer. The phase II evaluation of the combination of weekly irinotecan and cisplatin has shown encouraging response rates exceeding 30% to 50% in esophageal and gastric cancer. Hematologic toxicity using a schedule of 4 consecutive weeks of therapy followed by 2 weeks of rest prompted interest in a multicenter trial evaluation of a change in therapy delivery to 2 weeks on and 1 week off. Cisplatin at 30 mg/m2 was administered with irinotecan at 65 mg/m2, days 1 and 8, on an every-21-day schedule. Thirty-nine patients were entered on study, with 36 evaluable for toxicity and 31 evaluable for response. Grade 3/4 neutropenia was observed in only 22% of patients, reduced from 49% in a prior phase II trial employing 4 consecutive weeks of therapy. Confirmed major responses were observed in 36% of patients (10 of 28). A change to a day 1, day 8 schedule of weekly irinotecan and cisplatin appears to reduce hematologic toxicity but maintain antitumor activity in patients with esophageal and gastroesophageal junction cancer. A randomized phase II trial in gastric and esophageal cancer comparing weekly irinotecan and cisplatin to epirubicin, cisplatin, and 5-FU, and to infusional 5-FU in combination with irinotecan, will be conducted by the Cancer and Leukemia Group B (CALGB). A phase II trial combining this schedule of weekly cisplatin and irinotecan and concurrent radiotherapy given as preoperative therapy will also be conducted by the CALGB as a pilot trial.
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PMID:Phase II trial of weekly irinotecan/cisplatin in advanced esophageal cancer. 1568 30

The epidermal growth factor receptor (EGFR) plays an important role in cell growth, differentiation, and survival. Targeting EGFR in patients with colorectal cancer has become an important therapeutic tool. Recently, a monoclonal antibody against the extracellular domain of the receptor (cetuximab [Erbitux]) has been approved for the treatment of patients with EGFR-positive metastatic disease refractory to irinotecan (Camptosar)-based therapy. The role of other targeted agents against EGFR, including other monoclonal antibodies as well as inhibitors of the intracellular tyrosine kinase domain, will also be discussed.
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PMID:Epidermal growth factor receptor inhibitors and colorectal cancer. 1568 32

Irinotecan is a cornerstone drug in the management of metastatic colorectal cancer, as demonstrated by several randomized studies proving a survival benefit for the first time. In the adjuvant setting, FOLFOX (infusional 5-fluorouracil [5-FU]/leucovorin [LV] in combination with oxaliplatin) has improved 3-year disease-free survival in stage II/III colorectal cancer in the MOSAIC trial. Because 5-FU/LV-based combination therapy with oxaliplatin or irinotecan has similar efficacy in metastatic disease in the first-line setting, the impact of irinotecan in the adjuvant setting deserves further randomized clinical trials. Six such trials are ongoing or have already been closed to accrual, the results of which will be reported shortly. Five of these trials presently accruing patients or already closed combine irinotecan with an infusional regimen of 5-FU, based on a better tolerance and efficacy profile established in the metastatic setting according to clinical trials conducted principally in Europe. The results of 2 main randomized trials in the adjuvant therapy of stage III colon cancer will be presented at the 41st Annual Meeting of the American Society of Clinical Oncology in 2005 and are eagerly awaited. These results should provide important new insights as to how to manage stage II/III colon cancer.
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PMID:Irinotecan-based regimens in the adjuvant therapy of colorectal cancer. 1587 64


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