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)

Twenty-four patients with advanced metastatic cancer were treated with continuous intravenous 5-fluorouracil infusion 200-300 mg/m2/day and alpha interferon 3 million units subcutaneously 3 times per week. The average duration of treatment was 87 days (range 22-204 days). 5-fluorouracil could be infused 66% of the planned time on treatment, and patients received an average of 60% of the planned interferon injections. Objective tumor responses were seen in 6 of 17 previously untreated patients (35%). Twenty-two of the 24 patients (92%) experienced toxicity (greater than or equal to ECOG grade II) that required treatment interruption and subsequent dose reduction predominantly for the following reasons: mucositis (67%), hand-foot syndrome (21%), and leukopenia (25%). The incidence of treatment limiting toxicity is higher than previously observed with 5-fluorouracil infusion alone. This suggests true augmentation of 5-fluorouracil effect by interferon. 5-Fluorouracil infusion and alpha interferon is a potentially useful combination that needs further evaluation in future phase II and phase III trials.
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PMID:Continuous 5-fluorouracil infusion and alpha interferon in advanced cancers: a report of initial treatment results. 201 9

Thirty patients with Stage III non-small cell lung cancer were entered on a trial to evaluate the feasibility of combined radiation and concomitant 5-fluorouracil infusion. Patients had received prior debulking surgery (nine), induction chemotherapy (16), or no therapy (five). Radiation employed standard fractionation (180-200 rad/day) administered to a median cumulative dose of 5500 rad (range, 4500-6200 rad). 5-Fluorouracil was infused 24 hours per day throughout the period of radiation at a dose of 300 mg/m2/day for a median of 42 days (range, 28-56 days). Radiation complications included pneumonitis three of 30 (10%) and esophagitis (27%). Chemotherapy complications included stomatitis, two of 27 (7%), and hand-foot syndrome, three of 30 (10%). Treatment interruptions were necessary in six of 30 (20%) and four of 30 required parenteral nutrition. At a median follow-up of 12 months 26/30 (87%) maintained local control and eight had distant metastases (three of whom presented with Stage IV disease). 5-Fluorouracil delivered continuously throughout standard fractionation radiation to high cumulative doses is feasible and practical. Comparative clinical trials of the various combined radiation and chemotherapy schedules employed are in order. One additional clinical observation was the identification of six of 30 (20%) with brain metastases at presentation or after 12 months, all of whom had adenocarcinoma histologic subtype.
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PMID:Concomitant 5-fluorouracil infusion and high-dose radiation for stage III non-small cell lung cancer. 254 5

Low-dose continuous infusion 5-fluorouracil (LDCI-FU) was administered to 28 women with advanced breast carcinoma. Daily doses ranged from 175 to 250 mg/m2. The LDCI-FU was delivered continuously until the appearance of toxicity and was reinstituted at a 20% dose reduction after toxicity completely resolved. Patients with a median age of 56 years and a median performance status of 60% (Karnofsky) had been previously treated with combination chemotherapy. Complete responses were observed in two patients with soft tissue metastases. Thirteen patients experienced partial responses with a median duration of response of 4+ months. Partial responses were predominantly observed in soft tissue disease; however, five patients with visceral metastases experienced partial tumor regression. Median survival for the study group was 4+ months. Hormonal receptor status did not predict response to LDCI-FU. Toxicities included stomatitis, ten patients; hand-foot syndrome, eight patients; mild leukopenia, two patients; moderate thrombocytopenia, two patients; diarrhea, three patients; ataxia, three patients. Catheter-related toxicities of sepsis and/or thrombosis occurred in six patients. Because of the demonstrated activity in previously treated patients (53% response rate), LDCI-FU should be investigated in combination chemotherapy regimens in untreated breast cancer patients.
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PMID:Low-dose continuous infusion 5-fluorouracil. Evaluation in advanced breast carcinoma. 291 20

Thirteen patients with esophageal or gastroesophageal tumors with regional disease only were treated with sequential combined therapy. Weeks 1 to 6 continuous (24 hours) infusion 5-fluorouracil (5-FU) 300 mg/m2/d; weeks 6 to 10 or 12 infusional 5-FU administered concomitantly with radiation to the primary tumor site using standard fractionation with a cumulative median dose of 5000 rad; range 4400 to 6900 rad. Surgery was performed in five patients. All patients were evaluable for assessing response to the initial 5-FU infusion and 11/13 patients demonstrated tumor regression. Of 12 evaluable patients subsequently receiving combined infusional 5-FU and concomitant radiation, all 12 achieved complete clinical (10) or pathologic (two) tumor regression. Two of five patients having surgical resection had no pathologic evidence of tumor. All patients had relief of dysphagia within 1 week of initiating chemotherapy. Acute complications of therapy included stomatitis (two patients); hand-foot syndrome (two patients), and subclavian vein thrombosis (two patients). Stricture requiring periodic dilation occurred in three patients, and one patient developed a tracheoesophageal fistula at 36 months. Local control was maintained in 12/13 evaluable patients. Four of 13 patients were alive and without disease at 12 to 46 months. Nine patients died of distant metastases at 6 to 40 months. Median survival for the whole group was 16 months. Ten of the 13 patients (77%) survived for more than 1 year and 3/13 (22%) survived more than 3 years. This pilot study demonstrates the activity of 5-FU administered on an infusion schedule in both squamous and adenocarcinoma of the esophagus and the capacity to deliver infusional 5-FU throughout standard fractionation radiation. The local control and survival data may provide a basis for expanded Phase II trials, and a comparative trial against surgery alone might also be justified.
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PMID:Sequential infusional 5-fluorouracil followed by concomitant radiation for tumors of the esophagus and gastroesophageal junction. 359 64

Several studies suggest that protracted continuous infusion constitutes an important way to optimize the dose and the efficacy of 5-fluorouracil (5-FU) in metastatic cancer. Eighty-three women aged 27-76 (median age 55) with metastatic breast cancer were treated every 4 weeks with a continuous ambulatory venous infusion of 5-FU 350 mg/m2/day and oral cyclophosphamide 100 mg/m2/day over 15 days. The continuous therapy was associated with a weekly administration of vincristine (0.8 mg/m2) and doxorubicin (15 mg/m2) on day 1, day 8, and day 15. Cycles were repeated every 28 days. Thirty-four patients were treated in first-line metastatic chemotherapy and 49 in second-line. Toxicities included: mucositis (grade > or = 2) 23%, diarrhea (grade > or = 2) 7%, a hand-foot syndrome (grade > or = 2) 9%, alopecia (grade 3) 21%, neurological (grade > or = 2) 4%, grade 3 and 4 leukopenia 29%, and grade 3 and 4 thrombopenia 8%. Heart toxicity was only 3%. Catheter infection was observed in 1 case and 7 patients experienced thrombosis. The overall objective response rate (OR) was 48% and the complete response rate was 23%. The median duration of response was 10 months. The median survival was 16 months. Activity was better in naive than pretreated women (respectively, 55% and 42% of OR, p = 0.21). Analysis of responses according to the metastatic sites shows the pronounced efficacy on soft tissue diseases (skin recurrences 42%, lymph nodes 52%), and also in visceral metastases (hepatic 36%, lung 34%).
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PMID:Protracted continuous infusion of 5-fluorouracil in combination with doxorubicin, vincristine, and oral cyclophosphamide in advanced breast cancer. 859 3

A total of 55 patients with measurable colorectal metastatic carcinoma were studied to evaluate the impact on toxicity, response, and survival of protracted venous infusion (PVI) 5-FU 200 mg/m2 per day with Cis-DDP 80 mg/m2 or carboplatin 300 mg/m2 every 3 weeks, 1-hour infusion. Patients received continuous uninterrupted therapy until there were signs or symptoms of toxicity. Both 5-FU and cisplatin were withheld when patients experienced grade II stomatitis and diarrhea, severe nausea or vomiting not controlled by standard antiemetic therapy, and clinically significant hand-foot syndrome. The toxicity was neurological (20% grade 2 and 3) hematological (13% grade 2) and dermatological (11% grade 2). The overall response (CR+PR) was 24% with a median survival of 13 months. The results of our study show that there is no improvement in response rate, response duration or survival compared with historical trials. However, this study does confirm the valuable palliative role of the protracted 5-FU infusion treatment. Colorectal carcinoma is one of the most common neoplasms in Western societies, being second only to lung cancer as a cause of death from malignancy. The management of nonmetastatic primary disease in surgical, with adjuvant chemotherapy for those at high risk of relapse. However, for those with metastatic disease at diagnosis or recurrent disease after resection, cytotoxic chemotherapy is the treatment of choice and fluorouracil (5-FU) is the most active cytotoxic agent in this disease, with a response rate of approximately 20%. Efforts to improve the response rate have focused on the use of agents to modulate 5 FU. The Southwestern Oncology Group (SWOG) study reported by Leichman et al. (1) and a study from the United Kingdom by Hill et al. (2) compared conventional FU to modulated FU and found no improvement in response rate or survival. In the SWOG study, two different schedules of bolus FU and LV were compared with bolus FU alone and to continuous infusion FU administered alone or modulated by LV or PALA. In this study, the results obtained with bolus FU were superior to most of the studies in the literature: The response rate was 26%, and the median survival was 14 months. The high- and low-dose LV and FU groups showed response rates and survival similar to bolus FU alone. However, in 12 previously reported randomized studies comparing FU and LV or FU alone, nine reported that the combination of FU and LV produced significant increases in response rates and two reported significant increase in survival (3, 4). Many of these trials used the dose schedules reported in the SWOG trial. Protracted venous infusion (PVI) 5-FU has been shown to have superior efficacy with less toxicity in colorectal cancer when compared to bolus 5-FU and synergy between cisplatin and 5-FU has been demonstrated in vitro. Consequently, we have investigated the efficacy of the combination of bolus cis or carboplatin and PVI 5 FU in 55 patients with advanced colorectal cancer using survival, response rate, symptomatic response, and toxicity as study endpoints.
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PMID:First-line protracted venous infusion fluorouracil with CisDDP or carboplatin in advanced colorectal cancer. 922 28

Results from two phase II studies in metastatic breast cancer have shown that the novel, tumour-selective fluoropyrimidine capecitabine provides an effective and well tolerated therapy in patients with metastatic breast cancer failing or resistant to anthracycline and taxane therapy. Response rates of between 20 and 25% have been observed, with median survival of 12.2-12.6 months. In addition, there was an acceptable incidence of adverse events including diarrhoea and hand-foot syndrome, which can be controlled with a dose reduction. Promising results from two further randomised, phase II studies have indicated that capecitabine may also play a role in first- and second-line treatment of metastatic breast cancer. Capecitabine compared favourably with paclitaxel in anthracycline-resistant patients and with intravenous (i.v.) CMF (cyclophosphamide/methotrexate/5-fluorouracil (5-FU)) in post-menopausal women who had received no prior chemotherapy for metastatic disease, with high efficacy and good tolerability. The results of these four phase II studies demonstrate that capecitabine is active and well tolerated in a range of settings for metastatic breast cancer.
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PMID:Clinical experience of capecitabine in metastatic breast cancer. 1184 30

Anthracyclines, together with taxanes, are at present the most active agents in metastatic breast cancer, while single-agent, bolus 5-fluorouracil (5-FU) is not very active in this setting. In view of encouraging results and tolerable toxicity of continuous infusion of 5-FU in gastrointestinal cancer, innovative oral 5-FU agents such as capecitabine have been developed. Capecitabine is a prodrug that is converted into the active compound 5-FU preferentially at the tumor site. An intermittent dosing schedule of capecitabine twice daily at a dose of 2510 mg/m2/day on days 1-14 in a 3-week cycle appeared to be feasible and resulted in a high dose intensity. A large phase II study investigating capecitabine in 135 advanced breast cancer patients, pretreated with anthracyclines and taxanes, observed three complete and 24 partial responses (response rate, 20%), with a mean duration of 8.0 months. Preliminary results of a study comparing capecitabine with paclitaxel in 42 breast cancer patients failing anthracyclines indicate that the efficacy of capecitabine is comparable to that of paclitaxel, with response rates of 36% and 21%, respectively. Another study reported a response rate of 25% for capecitabine as first-line therapy for advanced breast cancer in women aged > or = 55 years, which tended to be better than combination chemotherapy with cyclophosphamide/methotrexate/5-FU. In all studies, capecitabine side effects were mainly mild, and treatment-related grade 3/4 toxicity consisted of diarrhea (8%-11%), nausea (4%-11%), hand-foot syndrome (10%-18%), neutropenia (3%-20%), and bilirubin elevation (6%). Capecitabine is clearly an active agent for the treatment of breast cancer. It is currently registered in various countries for use in third-line treatment of metastatic disease. Its further role will have to be defined from data of randomized phase III studies.
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PMID:Capecitabine in breast cancer: current status. 1189 51

Capecitabine, a tumor-selective, oral fluoropyrimidine, has demonstrated significant antitumor activity in patients with metastatic breast cancer. In this open-label monocenter phase II study the efficacy and safety of capecitabine in patients with metastatic breast cancer who relapsed after high-dose chemotherapy was examined. Female patients 18-65 years of age, with a histologically confirmed diagnosis of metastatic breast cancer, who relapsed after high-dose chemotherapy (adjuvant and/or metastatic) followed by autologous peripheral blood stem cell transplantation (PBSCT) and who had been treated in their course of the disease with an anthracycline and/or an anthracycline/taxane containing regimen were included into this clinical study. Capecitabine was applied as the first salvage chemotherapy at relapse after high-dose chemotherapy (1250 mg/m(2) b.i.d. p.o. for 14 days followed by 7 days rest period). Responding patients or those with stable disease after two treatment cycles were offered to continue treatment until tumor progression. Response rate, time to disease progression, survival, toxicity and quality of life were assessed. Fourteen patients between 35 and 60 years (median 45.5 years) entered this study and received a median number of 5 cycles (range 1-19) of capecitabine. All patients were evaluable for response. All patients had been pretreated with 1-2 cycles of high-dose chemotherapy plus PBSCT. Furthermore, 13 patients had additionally received local radiotherapy. On average, the patients showed metastatic disease in two organ sites (range 1-4 sites). One patient obtained a complete response and five patients a partial response, accounting for a response rate of 42.9% [95% confidence interval (17.7%; 71.1%)]. All responses were already achieved at the first observation time point 6 weeks after treatment initiation. Two further patients obtained stable disease for at least 12 weeks. At the time of final analysis all patients have progressed. Median time to progression was 2.8 months (range 0.4-13.3 months). No median survival time was reached (range 3.9-36.5 months, at the time of reporting eight patients were alive and six patients had died). Two patients developed grade III granulocytopenia. Five patients developed grade III hand-foot syndrome. One patient had the combination of nausea, fever and diarrhea grade III. All adverse events were considered manageable. We conclude that capecitabine as single-agent oral chemotherapy is active and well tolerated in heavily pretreated patients with breast cancer. It can be safely used in patients who have been intensively pretreated by myelotoxic chemotherapy or who have even relapsed after high-dose chemotherapy with PBSCT.
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PMID:Capecitabine in patients with breast cancer relapsing after high-dose chemotherapy plus autologous peripheral stem cell transplantation--a phase II study. 1198 86

Metastatic meningioma is a rare disease, which has no effective chemotherapy. We report on a treatment of this condition with Doxil, a liposomal doxorubicin formulation. A 60-year-old woman with massive pleuro-pulmonary metastases from recurrent cranial meningioma was treated with Doxil (50-37.5 mg/m2) for 18 months with near-complete resolution of metastases and disappearance of pleural fluid. The only significant toxicities observed were stomatitis and hand-foot syndrome, which resolved with dose reduction and increase of dosing intervals. Doxil was cleared very slowly in this patient with a monoexponential half-life of 108 h. The patient remains in near-complete response for 6 months after treatment discontinuation. This is the first report on an effective chemotherapy in a patient with typical metastatic meningioma. The exact mechanism accounting for such an effective drug action is not clear, but may be related to a particularly high microvascular permeability to the liposome carriers in these metastatic lesions.
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PMID:Doxil-induced regression of pleuro-pulmonary metastases in a patient with malignant meningioma. 1263 20


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