Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy and safety of gemcitabine at a starting dose of 800 mg m2 administered once a week for 3 weeks with 1 week's rest was investigated in chemonaive patients with advanced and/or metastatic pancreatic cancer. Of 34 patients, 32 were evaluable for efficacy, 20 patients had metastatic stage IV disease, 25 had a performance status of 1 and 26 (76%) patients has significant pain on presentation. All responses were independently validated by an external oncology review board: two patients achieved a partial response that lasted 5.8 and 5.2 months (6.3%) and six patients were stable for at least 4 weeks. The median duration of survival for evaluable patients was 6.3 months (range 1.6-19.2 months). The tumour markers, CEA, CA 19-9 and CA 195 were serially measured in 16 patients. There was a good correlation with tumour response when all three markers were significantly decreased. In 4 of 16 patients, tumour marker levels decreased by > or = 60%, including the two responders, one patient who survived for 12 months and one patient who showed objective tumour shrinkage but was deemed ineligible for response evaluation because the disease was considered not to be bidimensionally measurable. Symptomatic benefits included improvement in performance status (17.2%), analgesic requirement (7.4%), pain score (28.6%) and nausea (27.3%). The mean number of cycles administered was 2.5 and the mean dosage received was 890 mg m2 per injection. Seventy-four per cent of dose administrations were given on schedule. Toxicity, particularly haematological toxicity, reported as the maximum WHO grade experienced by patients was mild. Infective episodes were rare and limited to WHO grade 2 (6.7%). Nausea and vomiting was generally modest (WHO grade 3, 26.7%). Other side-effects included mild transient flu-like symptoms (seven patients) and peripheral oedema (three patients), which was not associated with abnormal cardiac hepatic or renal function. Gemcitabine has modest activity in pancreatic cancer, a limited positive improvement on a range of patient benefit parameters and has a mild toxicity profile. For these reasons and because of its novel mode of action, gemcitabine warrants further investigation in combination studies in pancreatic cancer.
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PMID:Phase II study of gemcitabine in patients with advanced pancreatic cancer. 855 69

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

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of gemcitabine are reviewed. Gemcitabine is a deoxycytidine-analogue antimetabolite with activity against some solid tumors. Gemcitabine is phosphorylated intracellularly to difluorodeoxycytidine triphosphate, which terminates DNA-chain elongation and competitively inhibits DNA polymerase and ribonucleotide reductase. After i.v. administration, gemcitabine is rapidly distributed into total body water. The drug is deaminated in the plasma to inactive difluorodeoxyuridine; both gemcitabine and difluorodeoxyuridine are primarily renally eliminated. In clinical studies, gemcitabine reduced pain and improved function in patients with advanced pancreatic cancer. Gemcitabine has shown some activity against non-small-cell lung cancer, particularly when combined with cisplatin or ifosfamide. The agent has also shown modest activity against advanced ovarian and breast cancer. Adverse effects include dose-limiting myelosuppression, flu-like symptoms, nausea, vomiting, and rash. Gemcitabine has FDA-approved labeling for use in the treatment of locally advanced and metastatic pancreatic cancer. The recommended dosage for this indication is 1000 mg/m2 (as the hydrochloride salt) i.v. given over 30 minutes weekly for seven weeks, followed after one week of rest by 1000 mg/ m2 i.v. given over 30 minutes weekly for three weeks every four weeks. Gemcitabine palliates symptoms in patients with advanced or metastatic pancreatic cancer. More study is needed to determine gemcitabine's role in the treatment of non-small-cell lung cancer, ovarian cancer, and breast cancer.
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PMID:Gemcitabine: a cytidine analogue active against solid tumors. 911 4

This phase I trial was initiated based on encouraging clinical data with 5-fluorouracil (5-FU)/leucovorin (LV), gemcitabine and cisplatin (G-FLIP) in the therapy of solid tumors. In this trial, G-FLIP has been modified to facilitate outpatient administration and to optimize sequence-dependent synergistic activity. Treatment consisted of biweekly (once every 14 days) cycles of sequential gemcitabine 500 mg/m, irinotecan per dose escalation schedule, bolus 5-FU 400 mg/m and LV 300 mg on day 1 followed by a 24-h 5-FU infusion 1500 mg/m, followed by cisplatin 35 mg/m on day 2. The irinotecan starting dose was 80 mg/m and escalated by 20 mg/m in cohorts of three patients until the maximum tolerated dose (MTD) was defined. Twenty-three patients were enrolled (13 men/10 women) with the following cancers: 11 pancreatic, five gallbladder, three squamous cell carcinoma of the head and neck, one hepatocellular carcinoma, one melanoma, one gastric, and one breast cancer. Median patient age was 63 years (range 44-78) and median Karnofsky performance status (KPS) was 80. Patients received a median of 8 cycles (range 1-16) over five irinotecan dose levels (80, 100, 120, 140 and 160 mg/m). Dose-limiting toxicity consisting of grade 3 nausea/vomiting despite aggressive anti-emetic therapy occurred in one patient at dose level 1 and three patients at dose level 3. Grade 3-4 hematological toxicities per patient consisted of thrombocytopenia (3%), anemia (6%), thrombosis (23%), neutropenia (16%) and neutropenic fever (10%). Of 18 patients evaluable for response, one complete response (pancreatic) and eight partial responses (three gallbladder, two pancreatic, two head and neck, and one breast) were attained. Seven patients had disease stabilization (five pancreatic, one hepatocellular and one gastric) for a median of 16 weeks (range 10-22). Median time to disease progression among all 23 patients enrolled to the phase I portion of the trial was 20.5 weeks (range 4-37). We conclude that G-FLIP is a novel outpatient chemotherapy regimen with acceptable toxicity at the maximum tolerated irinotecan dose of 120 mg/m. The phase II trial of G-FLIP using an irinotecan dose of 120 mg/m for patients with metastatic pancreatic cancer is ongoing.
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PMID:Phase I dose-finding study of biweekly irinotecan in combination with fixed doses of 5-fluorouracil/leucovorin, gemcitabine and cisplatin (G-FLIP) in patients with advanced pancreatic cancer or other solid tumors. 1501 53

The incidence of pancreatic cancer is about 10,000 cases a year in Germany. The role of surgery as a curative modality is limited. The 5-year survival for all stages remains less than 5%. Pain, cachexia, jaundice, nausea, fatigue and depression are frequent symptoms which reduce the quality of life for affected patients. Therefore, amelioration of symptoms is a major goal of palliative care. Chemotherapy may yield a moderate survival benefit. Gemcitabine is the drug of choice in metastatic pancreatic cancer. In locally advanced disease, radiochemotherapy can be considered. Different treatment strategies against molecular targets are currently tested in clinical trials.
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PMID:[Best supportive care of pancreatic carcinoma]. 1516 Feb 43

Early and late phase II studies of S-1 were conducted for the treatment of metastatic pancreatic cancer. In both trials, S-1 was administered at a dose of 80 mg/m2/day. One course consisted of consecutive administration of S-1 for 28 days, followed by 14 days of rest. This regimen was repeated every 6 weeks until the occurrence of progressive disease or unacceptable toxicities. The early phase II study demonstrated a response rate of 21.1% with a median survival time of 5.6 months in 19 patients. The major drug-related adverse events were gastrointestinal toxicities like nausea, and anorexia, though most of them were tolerable and reversible. Other treatment-related adverse events, like ileus, colitis, and abdominal distension, were less frequent. The late phase II study confirmed favorable responces with a mild toxicity profile in 40 evaluable patients. S-1 is active and well tolerated in patients with metastatic pancreatic cancer. Randomized trials are warranted to determine the effectiveness of S-1 for the treatment of pancreatic cancer.
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PMID:[S-1 monotherapy for pancreatic cancer]. 1689 4

Development of treatments to improve the outcomes achieved with single-agent gemcitabine therapy for metastatic pancreatic cancer remains a research priority. G-FLIP (gemcitabine, 5-fluorouracil, leucovorin and cisplatin) is a four-drug regimen designed to maximize sequence-dependent synergy, while attempting to minimize toxicity among the four drugs. The dose-limiting toxicities and maximum tolerated dose of irinotecan as part of the G-FLIP regimen have been published. For phase II testing, G-FLIP consisted of sequential gemcitabine 500 mg/m2 at a fixed rate of 10 mg/m2/min, irinotecan 120 mg/m2, bolus 5-fluorouracil 400 mg/m2 and leucovorin 300 mg, followed by a 24-h 5-fluorouracil infusion of 1500 mg/m2 on day 1 and cisplatin 35 mg/m2 on day 2. Cycles were repeated every 14 days. Thirty-three patients with metastatic pancreatic cancer (22 men and 11 women) were treated and 31 were evaluable. Median patient age was 63 years (range 44-78 years) and median Karnofsky performance status score was 70-80. Estimated median time to disease progression was 171 days (6.1 months) and Kaplan-Meir-estimated median overall survival was 229 days (8.1 months). Twelve- and 18-month survivals were 33 and 21%, respectively. As per Response Evaluation Criteria in Solid Tumors criteria, 13 patients had stable disease, seven (22%) attained a partial response, and 10 (32%) had disease progression. One patient attained a complete response and two were not evaluable (one withdrew consent and one died suddenly, each after cycle 1). Treatment generally was well tolerated. Grade 3-4 toxicities/patient were thrombocytopenia (3.1%), leukopenia (15%), neutropenia (21%), neutropenic fever (3%), fatigue (18%) and thrombosis (12.5%). Common grade 1-2 toxicities per patient included nausea/vomiting (69%), diarrhea (45%), constipation (21%) and fatigue (39%). In conclusion, G-FLIP is a feasible outpatient regimen with acceptable toxicity for metastatic pancreatic cancer patients. Disease control rate (stable disease rate plus partial or complete responses) and 1-year survival outcomes are encouraging.
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PMID:Pooled efficacy analysis from a phase I-II study of biweekly irinotecan in combination with gemcitabine, 5-fluorouracil, leucovorin and cisplatin in patients with metastatic pancreatic cancer. 1726 57

This study evaluated the antitumor effect and safety of S-1, an oral fluoropyrimidine derivative, in patients with metastatic pancreatic cancer. Chemo-naive patients with pancreatic adenocarcinoma, and measurable metastatic lesions were enrolled. S-1 was administered orally twice daily after meals at a dose of 80, 100, or 120 mg/day for body surface areas (BSAs) of less than 1.25 m(2), between 1.25 m(2) and less than 1.5, or 1.5 m(2) or greater, respectively, for 28 consecutive days, followed by a 14-day rest. Fifteen (37.5%) of 40 patients responded to treatment, including 1 complete response and 14 partial responses. The median time to progression and the overall survival time were 3.7 months (95% confidence interval, 2.2-5.6 months) and 9.2 months (95% confidence interval, 7.5-10.8 months), respectively. The major adverse events were anorexia, fatigue, hemoglobin reduction, nausea and pigmentation change, although most were tolerable and reversible. Although disseminated intravascular coagulation occurred in two patients, the condition resolved with anticoagulant therapy. S-1 is an effective and well-tolerated drug. The effectiveness of this drug should be confirmed in a phase III study.
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PMID:A late phase II study of S-1 for metastatic pancreatic cancer. 1752 Feb 53

The patient was a 70-year-old man with metastatic pancreatic cancer. After he received combination chemotherapy with gemcitabine and oral S-1 on day 1, he experienced severe general fatigue, anorexia and nausea. Then we changed the dose of gemcitabine from 1,000 mg/m(2) 2 to 500 mg/m(2) according to the criteria for an individual maximum repeatable dose (iMRD) determination method on day 8. His general condition recovered, and treatment schedule of gemcitabine with S-1 was continued sequentially at an outpatient clinic. His tumor marker levels, and the sizes of primary pancreatic tumor and liver metastatic lesions remarkably decreased. Partial response has been obtained for 7 months.
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PMID:[A case of advanced pancreatic cancer responding to combination chemotherapy with the individual maximum repeatable dose of gemcitabine and oral S-1]. 1863 36

Targeting the epidermal growth factor receptor pathway in pancreatic cancer seems to be an attractive therapeutic approach. This study assessed the efficacy of cetuximab plus the combination of gemcitabine/oxaliplatin in metastatic pancreatic cancer. Eligible subjects had histological or cytological diagnosis of metastatic pancreatic adenocarcinoma. The primary end point was response according to RECIST. Patients received cetuximab 400 mg m(-2) at first infusion followed by weekly 250 mg m(-2) combined with gemcitabine 1000 mg m(-2) as a 100 min infusion on day 1 and oxaliplatin 100 mg m(-2) as a 2-h infusion on day 2 every 2 weeks. Between January 2005 and August 2006, a total of 64 patients (22 women (34%), 42 men (66%); median age 64 years (range 31-78)) were enrolled at seven study centres. On October 2007, a total of 17 patients were alive. Sixty-two patients were evaluable for baseline and 61 for assessment of response to treatment in an intention-to-treat analysis. Six patients had an incomplete drug combination within the first cycle of the treatment plan (n=4 hypersensitivity reactions to the first cetuximab infusion, n=2 refused to continue therapy). Reported grade 3/4 toxicities (% of patients) were leukopaenia 15%, anaemia 8%, thrombocytopaenia 10%, diarrhoea 7%, nausea 18%, infection 18% and allergy 7%. Cetuximab-attributable skin reactions occurred as follows: grade 0: 20%, grade 1: 41%, grade 2: 30% and grade 3: 10%. The intention-to-treat analysis of 61 evaluable patients showed an overall response rate of 33%, including 1 (2%) complete and 19 (31%) partial remissions. There were 31% patients with stable and 36% with progressive disease or discontinuation of the therapy before re-staging. The presence of a grade 2 or higher skin rash was associated with a higher likelihood of achieving objective response. Median time to progression was 118 days, with a median overall survival of 213 days. A clinical benefit response was noted in 24 of the evaluable 61 patients (39%). The addition of cetuximab to the combination of gemcitabine and oxaliplatin is well tolerated but does not increase response or survival in patients with metastatic pancreatic cancer.
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PMID:Cetuximab plus gemcitabine/oxaliplatin (GEMOXCET) in first-line metastatic pancreatic cancer: a multicentre phase II study. 1929 97


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