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)

Oxaliplatin has shown in vivo cytotoxic activity against colorectal cell lines. Preliminary studies suggest potentiation of fluorouracil (5-FU). To assess this issue, we performed a phase II study in pretreated patients with advanced colorectal cancer (CRC) resistant to leucovorin and 5-FU. The regimen (FOLFOX2) consisted of oxaliplatin 100 mg/m2 as a 2-h infusion on day 1; leucovorin 500 mg/m2 as a 2-h infusion, followed by 5-FU 24-h infusion 1.5-2 g/m2 for two consecutive days every 2 weeks. The initial 5-FU dose was 1.5 g/m2 for two cycles and increased to 2 g/m2 in case of no toxicity > grade 2. 46 patients were treated, all with disease progression on leucovorin and 5-FU therapy for metastatic disease, or relapse less than 6 months after the end of adjuvant therapy. One complete response (CR) and 20 partial responses (PRs) were observed for an overall response rate of 46%. 22 patients had prior documented progression while receiving the same schedule of leucovorin and 5-FU as the one used in the FOLFOX2 regimen, and among them, 10 had PRs (45%). From the start of FOLFOX2, median progression-free survival was 7 months and median survival 17 months. WHO toxicity > or = grade 3 per patient was: peripheral neuropathy 9%, nausea 4%, diarrhoea 9%, mucositis 13%, neutropenia 39%, thrombocytopenia 11%, alopecia 9%, and allergy 2%. Overall, 21 patients (46%) experienced grade 3-4 toxicity. This combination of leucovorin, 5-FU and oxaliplatin achieves a high response rate in pretreated patients with CRC resistant to leucovorin and 5-FU. Limiting toxicities are neutropenia and peripheral neuropathy.
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PMID:Oxaliplatin with high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated metastatic colorectal cancer. 913 91

Patients with colorectal carcinoma progressing after a 5-fluorouracil (5-FU)-containing regimen were eligible. One treatment cycle consisted of repeated administrations of 5-FU combined to folinic acid for six times and to oxaliplatin for three times over 50 days. 5-FU was given at the dose of 2.6 g/m2 as a continuous infusion over 24 h on days 1, 8, 22, 29 and 43 preceded by i.v. folinic acid (FA) at a dose of 500 mg/m2 over 1 h. Oxaliplatin was given 1 h after 5-FU at the dose of 130 mg/m2 over a 2 h infusion on days 1, 22 and 43. A total of 37 patients were treated according to this schedule. The rates of objective responses after the first and second treatment cycles were 28 and 17%, respectively, with rates of tumor growth control, i.e. including the stabilizations, of 55 and 28%. The median duration of response was 10 months and the median duration of stabilizations was 6 months. The median survival time from initiation of oxaliplatin-containing therapy is 10 months (2-28+). The median survival time from the diagnosis of metastatic disease is 24 months (2-40+). The main toxicities were leucopenia, diarrhea, fatigue and paresthesias. The combination of 5-FU/FA/oxaliplatin was well tolerated and appears as a meaningful therapy after failure of a previous 5-FU-containing treatment.
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PMID:Oxaliplatin combined to 5-fluorouracil and folinic acid: an effective therapy in patients with advanced colorectal cancer. 963 19

A significant number of patients with colorectal cancer will present with hepatic metastases as their only site of metastatic disease. Surgical resection in patients with a limited number of metastases will lead to long-term survival in up to one-third. However, following surgery, many of these patients will relapse within the liver, and many will develop extrahepatic metastases. The use of hepatic artery infusion alternating with systemic therapy has proven to reduce the risk of recurrent disease and improve survival. Impressive response rates have been achieved with the combination of oxaliplatin and fluorouracil (5-FU) in patients with metastatic colorectal carcinoma. In one trial, this combination resulted in significant tumor shrinkage allowing resection of previously unresectable hepatic metastases. Given the promising activity of oxaliplatin (Eloxatin), 5-FU, and leucovorin, a trial is now in development to assess the efficacy of this combination when used together with hepatic artery infusion.
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PMID:Intrahepatic therapy for resected hepatic metastases from colorectal carcinoma. 1120 64

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

BACKGROUND: Up to now the cytostatic oxaliplatin was classified as nonvesicant. This is the first report on tissue necrosis induced by oxaliplatin extravasation in literature. A clinical course following oxaliplatin extravasation is reported. CASE REPORT: A 52-year-old white female with adenocarcinoma of the colon and hepatic and pulmonary metastases received palliative chemotherapy consisting of oxaliplatin, leucovorin, and 5-fluorouracil. By mistake oxaliplatin infusion extravasated subcutaneously in the left forearm; consequently, a painless red swelling occurred without any sign of further damage of the tissue. The infusion cannula was removed and oxaliplatin was infused into the right median cubital vein at the elbow. Again oxaliplatin extravasated subcutaneously. A severe painful necrotic reaction of the underlying flexor muscles of the right elbow developed, disabling the patient for 2 months, showing red-brown painful swelling, sclerosis of the skin, induration, fixation, and immobilization of the right elbow. Nonsteroidal analgesics and antibiotics were given, and lymphatic drainage and physiotherapy performed as generally accepted polypragmatic unspecific therapeutic procedure. After 2 months, the patient was able to bow and extend the right elbow except for an extension deficit of 20 degrees, pro- and supination became possible again, pain had completely resolved and strength recovered without limitation. Sclerosis of the skin and stiffness of the underlying tissue were slowly subsiding. CONCLUSION: Oxaliplatin can induce severe necrosis of underlying muscles by extravasation and therefore must be considered as a vesicant. Therefore oxaliplatin should be applied via a central venous access. Copyright 2000 S. Karger GmbH, Freiburg
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PMID:Extravasation of Oxaliplatin (Eloxatin((R))) - Clinical Course. 1144 Dec 43

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

When treating patients for metastatic cancer, there is always a balance between the benefits of treatment and resulting side-effects. Peripheral sensory neuropathy (PSN) is a side-effect of many anticancer agents used in routine practice. Oxaliplatin is a relatively new agent currently licensed in over 50 countries including France, Germany and the UK for the treatment of metastatic colorectal cancer. Although it is a new agent, it is from the same family of drugs as cisplatin, an agent that has been used for many years. PSN is the most commonly discussed side-effect associated with oxaliplatin. Oxaliplatin-induced PSN is characterized by two distinct syndromes: a transient acute dysaesthesia and a cumulative distal neurotoxicity. Importantly, both are generally reversible after stopping treatment. Oxaliplatin-induced acute PSN is triggered and exacerbated by cold and can be greatly reduced in affected patients simply by avoiding cold conditions. Oxaliplatin-induced cumulative PSN may also be managed by temporary cessation of treatment.
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PMID:An overview of chemotherapy-induced peripheral sensory neuropathy, focusing on oxaliplatin. 1195 4

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

Oxaliplatin, a platinum compound characterized by a diaminocyclohexane (DACH) platinum carrier ligand, has proven its efficacy in first- and second-line advanced colorectal cancer (CRC) treatment. Acute reversible and cumulative peripheral sensory neuropathy has been observed frequently with oxaliplatin treatment and limits its use. Its synergism with other drugs, as well as its different mechanism of action and toxicity profile make it an attractive candidate for combination studies in CRC. It can be combined safely with 5-fluorouracil (5-FU)+/-folinic acid (LV), irinotecan, raltitrexed, multitarget antifolate LY231514 (MTA), and oral 5-FU prodrugs. These combinations confer both an increased response rate compared to that of any single agent and an increased secondary surgical resection of initially unresectable metastases, possibly leading to prolonged survival. In three prospective randomized phase III studies in advanced CRC, oxaliplatin plus 5-FU/LV improved significantly progression-free survival without a significant increase in median survival time and without affecting quality of life, compared to treatment with 5-FU/LV. Ongoing clinical trials will define its role in the adjuvant setting.
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PMID:Oxaliplatin: results in colorectal carcinoma. 1239 98

Oxaliplatin, which was recently approved by the US Food and Drug Administration for the treatment of advanced colorectal cancer, is often administered to patients with altered liver function caused by hepatic metastases. Because of the absence of data on the clearance of oxaliplatin in patients with liver dysfunction, and to develop dosing recommendations for the safe use of oxaliplatin in this clinical setting, the Organ Dysfunction Working Group of the National Cancer Institute performed a phase I and pharmacokinetic trial of this drug in patients displaying a wide range of liver function abnormalities. Sixty patients grouped into five classes of liver function were enrolled in this study, including a 12-patient control group with normal liver function, 15 patients with "mild," 16 patients with "moderate," and 16 with "severe" liver dysfunction, as well as one patient who had undergone liver transplantation. The patients had a median age of 62 years and a Eastern Cooperative Oncology Group performance status of 0. All patients had received prior systemic chemotherapy, and 70% had a diagnosis of a gastrointestinal malignancy. The control patients were treated with 130 mg/m(2) oxaliplatin intravenously every 21 days; the starting doses for patients with mild, moderate, or severe liver dysfunction or post-liver transplantation were 105, 80, or 60 mg/m(2), respectively. Cohorts of three or more patients were escalated from these starting doses to 130 mg/m(2) if dose-limiting toxicities were not observed, and pharmacokinetic evaluations were performed at each dose level for every category of liver dysfunction. We found that oxaliplatin was well tolerated at its recommended dose and schedule of 130 mg/m(2) every 21 days in patients with all levels of liver dysfunction, and that there was no apparent alteration in the clearance of either total or ultrafilterable platinum species from plasma, even in patients with severe hepatic functional abnormalities.
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PMID:Pharmacology of oxaliplatin in solid tumor patients with hepatic dysfunction: a preliminary report of the National Cancer Institute Organ Dysfunction Working Group. 1452 90


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