Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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.
 ...
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.
 ...
PMID:A phase II study of continuous-infusion 5-fluorouracil with cisplatin and epirubicin in inoperable pancreatic cancer. 863 Feb 89

Patient with pancreatic have a median age of 78 years and without treatment an average survival of only a few months. Tumor stage and patient will determine the therapy. Patients with metastases or a high surgical risk are treated symptomatically. Jaundice, nausea, pain, and anorexia are the most relevant symptoms. The main symptom requiring treatment are jaundice and pruritus due to extrahepatic biliary obstruction which can be relieved in most cases by endoscopic placement of a biliary endoprosthesis. Pancreatic cancer may be a highly painful disease. Therapeutic modalities include, in addition to antitumoral treatment, narcotic and nonnarcotic analgesics, neurolytic celiac blockage, psychological support, and the treatment of associated symptoms such as emesis and constipation. Although radio- or chemotherapy show positive responses in a subgroup of patients, average survival remains unchanged with monotherapy. In contrast, improved median survival following combined radio-and chemotherapy has been demonstrated both in patients with locally unresectable pancreatic cancer and in patients after curative tumor resection.
 ...
PMID:[Pancreatic carcinoma: conservative and adjuvant therapy]. 868 57

An early phase II cooperative study of Gemcitabine Hydrochloride (abbreviated to "gemcitabine" herewith) was conducted in patients with a variety of solid tumors (i.e., lung cancer, gastric cancer, pancreatic cancer, colon/rectum cancer, cervical cancer, ovarian cancer and breast cancer) at 56 institutions. The aim of the first step (Step I) was to investigate the feasibility of gemcitabine in a variety of different solid tumors, including lung cancer regarding efficacy and safety. The aim of the second step (Step II) was as a result of step I (Responses were observed) to continue to investigate the efficacy and safety of gemcitabine in chemonaive patients with non-small cell lung cancer. As a Step I study, gemcitabine was administered once weekly at a dose of 800 mg/m2 for a consecutive 3-week period followed by a week of rest, in multiple courses. Among the 29 eligible patients with lung cancer, partial response (PR) was achieved in 3 patients (25.0%, 95% confidence interval: 5.5-57.2%) out of 12 chemonaive patients. Adverse reactions (grade 3 or higher) seen in 29 patients with lung cancer were neutropenia (27.6%), leukopenia (13.8%), decreased hemoglobin (13.8%), thrombocytopenia (10.3%), malaise (6.9%), anorexia (3.4%), nausea/vomiting (3.4%), diarrhea (3.4%), dyspnea (3.4%) and interstitial pneumonia (3.4%). In other types of solid tumors, PR was achieved in 2 (8.7%) out of 23 eligible patients with cervical cancer and in 1 (5.3%) of 19 eligible patients with ovarian cancer, while the use of analgesics became unnecessary in 1 patient with pancreatic cancer. Incidence as well as severity of main adverse reactions in these patients were comparable to those seen in patients with lung cancer. A Step II study, in which gemcitabine was administered once weekly at a dose of 1,000 mg/m2 to chemonaive patients with non-small cell lung cancer, was conducted, referring to the results of Step I and clinical studies conducted overseas. The results of the Step II study demonstrated PR in 5 (14.3%, 95% confidence interval: 4.8 - 30.3%) out of 35 eligible patients with non-small cell lung cancer and that the main adverse reactions were comparable to those seen in the Step I study, posing no tolerability problems in particular.
 ...
PMID:[An early phase II study of gemcitabine hydrochloride (LY 188011). Gemcitabine Cooperative Study Group for Early Phase II]. 893 92

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.
 ...
PMID:Gemcitabine: a cytidine analogue active against solid tumors. 911 4

Patients with advanced adenocarcinomas of the pancreas have an exceptionally poor prognosis. Modest activity has been demonstrated with single agents (response rates of 25% at best with 5-fluorouracil [5-FU] and mitomycin). Better results have not been obtained by combination chemotherapy. Improvements in the palliation have been achieved by treatment with 5-FU, folinic acid (FA), and interferon-alpha-2A (IFN-alpha) weekly in the context of a phase II trial. Of 57 evaluable patients, eight (14%) had a partial response (PR), eight (14%) a minor response (MR), and 28 (49%) had no change of disease (NC). The median survival time was 10 mo for patients with progressive disease. Twenty-two out of 36 patients with tumor-related pain whose tumors were affected in terms of PR, MR, and NC became free of pain during treatment. Fever (56%), nausea (37%), and diarrhea (33%) were common toxicities observed. Therefore, biochemical modulation of 5-FU with FA and IFN-alpha shows some positive effects in the treatment of pancreatic cancer with moderate toxicity.
 ...
PMID:Chemotherapy in advanced pancreatic cancer. 912 72

Chemotherapy treatment for advanced pancreatic cancer is universally disappointing. Evidence suggested the possibility of improved activity of 5-fluorouracil (5-FU) in this disease when administered by continuous infusion in combination with interferon-alpha. Thirteen patients who had histologically documented stage III and IV adenocarcinoma of the pancreas were treated with 5-FU, 250 mg/m2/day by continuous infusion, in combination with interferon-alpha, 3 million units subcutaneously 3 times per week. Treatment was adjusted for toxicity and was continued until disease progression, unacceptable toxicity, or 8 weeks after a complete response. Responses were documented on two separate occasions that were separated by 4 weeks. Eleven men and two women were treated an average of 48 days. There was one responder, for a response rate of 7.7% (95% confidence interval, 0.1%-36%). The duration of response was 90 days. The median survival of the entire group was 8.3 months. Toxicity was significant, with more than 50% of patients requiring treatment breaks and dosage reductions. The most common toxicities were mucositis, hand-foot syndrome, diarrhea, and nausea. There were no treatment-related deaths. Treatment of advanced adenocarcinoma of the pancreas with continuous-infusion 5-FU and interferon-alpha is associated with significant toxicity without significant evidence of response.
 ...
PMID:Continuous venous infusion 5-fluorouracil and interferon-alpha in pancreatic carcinoma. 953 1

An effective local-regional therapy is needed for adenocarcinomas of the pancreas. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton NJ) may enhance the effect of radiation therapy. Paclitaxel synchronizes cells at G2/M, a relatively radiosensitive phase of the cell cycle. We have shown that response to paclitaxel and concurrent radiation (paclitaxel/RT) was not affected by p53 mutations in non-small cell lung cancer (NSCLC). This suggested that paclitaxel/RT was a rationale treatment approach for other malignancies which frequently harbor p53 mutations such as upper gastrointestinal malignancies. We have completed a phase I study of paclitaxel/RT for locally advanced pancreatic and gastric cancers. The maximum tolerated dose (MTD) of paclitaxel was 50 mg/m2/week for 6 weeks with abdominal radiation. The dose limiting toxicities were abdominal pain within the radiation field, nausea and anorexia. Twenty-five patients with locally advanced pancreatic cancer have now completed treatment at the phase II dose level of paclitaxel 50 mg/m2/week with 50 Gy concurrent RT. Thus far, the only grade 3/4 toxicities have been hypersensitivity reactions in 2 patients, asymptomatic grade 4 neutropenia in 3 patients, and non-neutropenic biliary sepsis in 1 patient. Of the first 22 assessable patients treated at the phase II study, 8 obtained a partial response (PR) for a preliminary response rate of 36%. These findings demonstrate that paclitaxel/RT is well tolerated with substantial activity for locally advanced pancreatic cancer.
 ...
PMID:Paclitaxel and concurrent radiation for locally advanced pancreatic carcinoma. 979 3

Multiple studies have shown that leucovorin-fluorouracil regimens are modestly superior to fluorouracil alone in the treatment of advanced colorectal cancer. Laboratory data suggest that iododeoxyuridine could further enhance the efficacy of leucovorin-fluorouracil regimens. This report describes the Phase I clinical evaluation of a leucovorin-fluorouracil-iododeoxyuridine chemotherapy regimen. Twenty-four patients received treatment with leucovorin (500 mg/m2), fluorouracil (500 mg/m2), and iododeoxyuridine (escalating doses) on days 1 and 8 of a 21-day cycle. The maximum tolerated dose of iododeoxyuridine was 1200 mg/m2, with a recommended Phase II dose of 1000 mg/m2. Myelosuppression (leukopenia) was dose limiting; other commonly observed treatment toxicities were nausea/vomiting, mucositis, and hyperlacrimation. Although the 1200 mg/m2 dose was tolerated during the initial few cycles of therapy, chronic administration could not be maintained secondary to dose-limiting neutropenia. Since neutropenia was dose limiting, in a follow-up study, 10 patients received a modified regimen (treatment on days 1 and 6 instead of days 1 and 8) with the addition of granulocyte colony-stimulating factor (days 8-19). The addition of granulocyte colony-stimulating factor, however, did not permit further escalation of the iododeoxyuridine dose. Three partial responses and six minor responses were observed. Phase II studies of this regimen are ongoing in advanced colorectal and advanced pancreatic cancer to determine response rates in these diseases.
 ...
PMID:Biochemical modulation in the treatment of advanced cancer: a study of combined leucovorin, fluorouracil, and iododeoxyuridine. 981 23

Pancreatic cancer is widely regarded by medical personnel and the lay public as one of the most dreaded of all diagnoses. Although in selected series of operable patients the chance of long term survival may reach 20%, most patients have unfavourable disease at the time of diagnosis, and for the entire group of newly diagnosed patients, 5-year survival is rare. This grim outlook results from a combination of factors, including an anatomical location which makes early detection by screening tests or by symptoms difficult, a high tendency for spread to regional lymphatics and the liver, a poor profile of sensitivity to chemotherapeutic agents and the poor medical condition of many patients at the time of diagnosis. These factors mean that it is particularly important that at the time of diagnosis these patients are carefully evaluated, and that they and their families are fully aware of the treatment options available to them and the associated potential risks and benefits. For localised cancers, surgical resection alone offers the potential for long term survival. The addition of postoperative radiation therapy (RT) predictably improves local control but has minimal impact on survival, which is primarily determined by the development of liver metastases. Randomised trial data support the use of combined fluorouracil (5-FU) chemotherapy and RT in patients who have undergone pancreatectomy and have negative margins, although the benefits are modest and the relevant randomised trials enrolled relatively small patient numbers. For patients with marginally resectable tumours, the feasibility has been demonstrated of using chemotherapy plus RT to reduce tumour size before resection, but it is unclear whether this approach will benefit a significant number of patients. Tumours which are unresectable because of local advancement (involvement of major vessels or regional nodes) can be treated with RT alone or in combination with chemotherapy, but survival past 2 years is uncommon. Patients with liver metastases have a poor prognosis. As part of a programme of supportive care, some of these patients may receive cytotoxic therapy, the goal of which is to relieve cancer-related symptoms such as pain from the primary tumour or metastatic sites, or weakness, nausea and anorexia which may be associated with liver metastases. Although the objective response rate of chemotherapy agents is low, in an individual patient they may produce an adequate response and acceptable toxicity so that the patient experiences overall improvement in symptoms. The mainstay of chemotherapy for pancreatic cancer, as with other gastrointestinal cancers, has been fluorouracil. However, recent clinical data have shown that gemcitabine produces similar results in terms of response rate and survival, with more acceptable toxicity, so that the quality of life was judged to be better than with fluorouracil. Pancreatic cancer provides a fertile ground for testing new, biologically based approaches to cancer therapy because of the limited success of currently available treatments.
 ...
PMID:Practical recommendations for the management of adenocarcinoma of the pancreas. 995 52


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>