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)

The glucagonoma syndrome is a rare disorder characterized by weight loss, necrolytic migratory erythema (NME), diabetes, stomatitis, and diarrhea. We identified 21 patients with the glucagonoma syndrome evaluated at the Mayo Clinic from 1975 to 1991. Although NME and diabetes help identify patients with glucagonomas, other manifestations of malignant disease often lead to the diagnosis. If the diagnosis is made after the tumor is metastatic, the potential for cure is limited. The most common presenting symptoms of the glucagonoma syndrome were weight loss (71%), NME (67%), diabetes mellitus (38%), cheilosis or stomatitis (29%), and diarrhea (29%). Although only 8 of the 21 patients had diabetes at presentation, diabetes eventually developed in 16 patients, 75% of whom required insulin therapy. Symptoms other than NME or diabetes mellitus led to the diagnosis of an islet cell tumor in 7 patients. The combination of NME and diabetes mellitus led to a more rapid diagnosis (7 months) than either symptom alone (4 years). Ten patients had diabetes mellitus before the onset of NME. No patients had NME clearly preceding diabetes mellitus. Increased levels of secondary hormones, such as gastrin (4 patients), vasoactive intestinal peptide (1 patient), serotonin (5 patients), insulin (6 patients, clinically significant in 1 only), human pancreatic polypeptide (2 patients), calcitonin (2 patients) and adrenocorticotropic hormone (2 patients), contributed to clinical symptoms leading to the diagnosis of an islet cell tumor before the onset of the full glucagonoma syndrome in 2 patients. All patients had metastatic disease at presentation. Surgical debulking, chemotherapy, somatostatin, and hepatic artery embolization offered palliation of NME, diabetes, weight loss, and diarrhea. Despite the malignant potential of the glucagonomas, only 9 of 21 patients had tumor-related deaths, occurring an average of 4.91 years after diagnosis. Twelve patients were still alive, with an average age follow-up of 3.67 years.
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PMID:The glucagonoma syndrome. Clinical and pathologic features in 21 patients. 860 27

Carcinomas of the exocrine pancreas respond poorly to most chemotherapy regimens. Recently continuous infusional 5-fluorouracil (200 mg m-(2)day-1) with 3 weekly cisplatin (60 mg m-2) and epirubicin (50 mg m-2) (the ECF regimen) has proven to be an active regimen in gastric and breast cancer and consequently worthy of further study in pancreatic cancer. Thirty-five patients were treated with the ECF regimen as above, of whom 29 were evaluable for response and 32 were evaluable for toxicity. The mean age was 59 years (range 37-75). Sixteen patients had locally advanced disease at presentation and 19 had metastases. Objective tumour responses were documented in five (17.3%) patients who achieved a partial response; in 18 (62%) patients there were no change and six (20.7%) patients progressed on therapy. Patients with either stable disease or partial response had a significantly improved overall survival (median = 253 days) compared with patients who progressed (median = 170 days; P = 0.01). Grade 3/4 (WHO) toxicity (all cycles) included alopecia in 18 (56%) patients, nausea/vomiting in eight (25%) stomatitis in three (9%) and diarrhoea in seven (22%) patients, with rhinorrhoea and excessive lacrimation in one patient each. Neutropenic sepsis occurred in 13 cycles in ten patients, and there was one toxic death due to sepsis. There were eight other episodes of non-neutropenic sepsis requiring hospital admission. Fourteen patients (40%) experienced complications with their Hickman lines, including thrombotic episodes (six patients) or their line falling out (five patients). ECF can prolong survival in patients with locally advanced or metastatic pancreatic cancer who demonstrate a response or stabilisation of their disease. However, this is associated with considerable toxicity.
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PMID:A phase II study of continuous-infusion 5-fluorouracil with cisplatin and epirubicin in inoperable pancreatic cancer. 863 Feb 89

33 women with advanced breast cancer resistant to anthracyclines were treated with paclitaxel 175 mg/m2 in a 3 h infusion every 3 weeks. The median age was 53 years (range 30-72) and the median performance status was 1 (range 0-2). 24 (73%) patients had visceral metastases while 22 (67%) had > or = two involved sites. 23 (70%) patients received anthracycline or mitoxantrone in an adjuvant setting and 21 (64%) for advanced disease. There were two (6%, 95% confidence interval (CI) 1-20%) complete responses (CRs) and 12 (36%, 95% CI 20-55%) partial responses (PRs). Median dose intensity of paclitaxel delivered was 58 mg/m2/week. Median time to progression was 24 weeks (range 4-61) and median survival was 41 weeks (range 8-66). Grade 3-4 toxicities included leucopenia (9%), stomatitis (3%), alopecia (91%), neurotoxicity (9%), infection (3%) and diarrhoea (3%). In conclusion, paclitaxel at a dose of 175 mg/m2 exhibits significant activity in advanced breast cancer resistant to anthracyclines.
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PMID:A phase II study of paclitaxel in advanced breast cancer resistant to anthracyclines. 869 40

A comparative, randomized trial was conducted to determine the efficacy of oral UFT (Tegafur and Uracil) versus 5-fluorouracil (5-FU) in combination with cyclophosphamide and doxorubicin in patients with metastatic breast cancer. Of 62 evaluable patients, 31 received UFT (350 mg/m2/day orally x 14 days), doxorubicin (50 mg/m2 intravenously [I.V.] day 1) and cyclophosphamide (500 mg/m2 I.V. day 1). The other 31 patients received 5-FU (500 mg/m2 I.V. days 1 and 8), doxorubicin (50 mg/m2 I.V. day 1), and cyclophosphamide (500 mg/m2 I.V. day 1). Regimens were repeated for a total of six cycles. The two groups were comparable in terms of age, gender, performance status, menopausal status, and number and sites of metastases. No statistical difference in overall response rates was seen (UFT arm, 48.4% vs. 5-FU arm, 35 %; p = 0.30). Median response duration was 16 weeks (range, 4-30) for both arms. The toxicity profile (alopecia, anemia, leukopenia, thrombocytopenia, diarrhea) was similar in both groups and both regimens were well tolerated. Anemia and stomatitis were significantly more common in the 5-FU arm (p = 0.02). Thus, oral UFT has response rates and duration of response that are comparable to 5-FU in a combination regimen for advanced breast cancer.
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PMID:A comparative, randomized trial of UFT and 5-fluorouracil in combination with cyclophosphamide and doxorubicin in the treatment of advanced breast cancer patients at The Philippines General Hospital. 897 77

Advances in vascular radiology techniques for superselective transfemoral arterial infusion prompted us to evaluate the effects of high-dose rapid regional carboplatin infusion for patients with advanced head and neck squamous cell carcinomas. Twenty untreated patients received three infusions of carboplatin (300-350 mg/m2) every 2 weeks with this method. All the infusions were performed without any complication. Treatment was well tolerated, with moderate (Grade 1-3 WHO) local toxicity (stomatitis, dermatitis and alopecia) and minimal (Grade 1-2 WHO) myelosuppression. The total response index (complete response plus partial response) was 94% for primary tumors and 50% for neck metastases. Neoadjuvant chemotherapy employing superselective rapid infusion of high-dose carboplatin is a feasible, relatively nontoxic, effective technique and may have important applications in multimodality therapy of untreated patients with advanced head and neck cancer.
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PMID:[High-dose carboplatin superselective intraarterial chemotherapy in advanced head and neck cancer]. 898 37

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) appears to be one of the most active drugs in the treatment of advanced head and neck cancer. The maximum tolerated dose of paclitaxel in combination with carboplatin is currently being evaluated in phase I/II studies. We designed a phase II study to evaluate the activity and acute and cumulative toxicity of this combination in patients with recurrent or metastatic cancer of the head and neck. Chemotherapy consisted of paclitaxel 200 mg/m2, given as a 3-hour infusion, and carboplatin dosed to an area under the concentration-time curve of 7 mg x min/mL, administered every 28 days. Granulocyte colony-stimulating factor (5 microg/kg) also was given on days 2 to 12 of each cycle. At the time of this report, 41 patients had entered this study. Primary sites included the nasopharynx (10 patients), larynx (18), oral cavity (three), oropharynx (six), hypopharynx (three), and unknown (one). Among 25 evaluable patients with non-nasopharyngeal cancer, there were two complete responses and three partial responses, for an overall response rate of 20% (95% confidence interval, 4% to 36%). Among eight evaluable patients with nasopharyngeal cancer, four achieved a complete response and two a partial response. Grade 3 to 4 toxicities included anemia (2.5%), leukopenia (7.5%), thrombocytopenia (5%), vomiting (5%), stomatitis (2.5%), and infection (5%). These preliminary data indicate that the combination of paclitaxel and carboplatin is active against advanced head and neck cancer, particularly when used in the treatment of nasopharyngeal cancer.
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PMID:Paclitaxel and carboplatin in recurrent or metastatic head and neck cancer: a phase II study. 904 40

Gene therapy may be an important adjuvant for treating cancer in the pleural space. The initial results of retroviral gene transfer to cancer cells in malignant pleural effusions revealed that transduction was markedly inhibited, and studies to characterize the inhibitory factor(s) were performed. The inhibition was contained within the soluble, rather than cellular, components of the effusions and was demonstrated with amphotropic, gibbon ape leukemia virus, and vesicular stomatitis virus-glycoprotein pseudotyped retroviral vectors. After excluding complement proteins, a series of studies identified chondroitin sulfates (CSs) as the inhibitory substances. First, treatment of the effusions with mammalian hyaluronidase or chondroitinases, but not Streptomyces hyaluronidase, abolished the inhibitory activity. Second, addition of exogenous CS glycosaminoglycans mimicked the inhibition observed with pleural effusions. Third, immunoassays and biochemical analyses of malignant pleural effusion specimens revealed CS in relevant concentrations within pleural fluid. Fourth, proteoglycans/glycosaminoglycans isolated from the effusions inhibited retroviral gene transfer. Analyses of the mechanism of inhibition indicate that the chondroitin sulfates interact with vector in solution rather than at the target cell surface. These results suggest that drainage of the malignant pleural effusion, and perhaps enzymatic pretreatment of the pleural cavity, will be necessary for efficient retroviral vector mediated gene delivery to pleural metastases.
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PMID:Retroviral gene transfer is inhibited by chondroitin sulfate proteoglycans/glycosaminoglycans in malignant pleural effusions. 911 27

We performed a Phase II trial of edatrexate in 44 chemotherapy-naive patients with advanced renal cell carcinoma. Prior therapy with one biological-response modifier was permitted. Most patients had multiple sites of metastatic disease and were considered to have a poor prognosis using Eastern Cooperative Oncology Group criteria. Edatrexate was administered intravenously at a dose of 80 mg/m2 weekly with 5 weeks of therapy considered one cycle. Oral cryotherapy using ice chips was administered before each edatrexate dose. Thirty-seven patients were eligible and evaluable for toxicity and response. Two patients obtained a partial response, for an overall response rate of 5.4% (95% confidence interval of 0.6%, 18.2%); one patient remained in remission at 26+ months. Three treatment-related deaths occurred. Toxicity was severe, with stomatitis, myelosuppression, and other gastrointestinal side effects most prominent. Edatrexate in this dose and schedule has minimal activity in advanced renal cell carcinoma and is toxic.
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PMID:A phase II trial of edatrexate in patients with advanced renal cell carcinoma. An Eastern Cooperative Oncology Group study. 916 47

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

In this phase II trial we have evaluated the activity and toxicity of a combination regimen containing mitoxantrone, L-leucovorin, and fluorouracil in patients with advanced breast cancer pretreated with anthracyclines. Forty-six patients were included into the study; they received a total of 227 cycles of chemotherapy. Median age was 63 years (range 34-78), median performance status was 80 (range 60-100). Visceral metastases were present in 37 patients, 6 patients had bone involvement only, while 3 patients had soft tissue/lymph node disease. Median number of previous chemotherapy regimens for advanced disease was 2 (range 1-3). Ten patients had anthracycline primary resistance (progressive disease during treatment). Twenty-three patients received mitoxantrone 12 mg/sqm day 1; fluorouracil 370 mg/sqm and L-folinic acid 100 mg/sqm days 1-3 administered every three weeks. Another group of 23 patients were treated with the same regimen using a prolonged 5FU/L-FA schedule (5 days). Two complete responses and 6 partial responses were recorded with the 3-day schedule; 7 partial responses in the 5-day schedule (overall response rate 32.6%, 95% C.I. 19-46%). Two partial responses were observed in patients with anthracycline primary resistance. Median response duration was 9 months (range 3-16). Hematologic toxicity was mild: grade 3-4 leukopenia was recorded in 5 patients, grade 3-4 thrombocytopenia in 3 patients. Grade III-IV stomatitis and diarrhea was recorded in 4 and 5 patients respectively (all receiving the 5-day 5-FU/L-FA schedule). Cardiac toxicity was observed in two cases. This regimen proved active in advanced breast cancer following anthracycline-containing chemotherapy, and the 3-day schedule could be offered to such patients with acceptable toxicity.
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PMID:Mitoxantrone, fluorouracil, and L-folinic acid in anthracycline-pretreated metastatic breast cancer patients. 938 63


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