Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gemcitabine (GEM) is a novel deoxycytidine analogue which has shown promising antitumor activity in solid tumor models and a broad range of schedule-dependent MTDs (12-4560 mg/m2) in preliminary clinical studies. The present phase I trial evaluated escalating doses of weekly GEM using a 30-min infusion at a starting dose-level of 300 mg/m2/wk x 3 every 28 days. At least 3 patients entered each dose-level step and 3 more cases were treated when significant toxicity was seen. A total of 39 patients with various advanced solid tumors and prior chemotherapy entered this study. Six escalation steps (102 courses) were tested to define the MTD at 1,370 mg/m2/wk. No definite dose-effect relationships were observed for myelosuppression up to 1,095 mg/m2/wk. However, increased severity of leucopenia (dose-limiting) and greater non-hematologic toxicity as well as a higher number of toxic treatment delays, requiring subsequent dose attenuation in 6 out of 12 patients, were observed at 1,370 mg/m2/wk. In all, 6 out of 11 patients experiencing WHO grade > or = 3 toxicity (11/21 events recorded in 11/18 courses) were treated at the MTD. Clinically significant toxicity included (patients with WHO grade 2-3): leucopenia (44%), thrombocytopenia (26%), anemia (23%), fever (69%), emesis (38%) and AST/ALT rise (26%). Mild proteinuria, ankle edema, skin rash, hair loss and mucositis were seen in < or = 5%.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Weekly gemcitabine in advanced or metastatic solid tumors. A clinical phase I study. 786 Feb 27

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

To determine the activity and toxicity of gemcitabine (2',2'-difluorodeoxycytidine), three phase II single-agent studies have been conducted in patients with non-small cell lung cancer in Japan. In an early phase II study, 17 previously treated and 47 untreated patients were treated with gemcitabine. Gemcitabine was given intravenously at a dose of 800 mg/m2 or 1,000 mg/m2 once a week for 3 weeks followed by a week of rest, repeating every 4 weeks. Although none of the patients with prior therapy responded, eight (17%) of 47 previously untreated patients showed a partial response. Toxicities of grade 3 or greater included leukopenia (12.5%), thrombocytopenia (6.3%), and anemia (15.6%). We entered 73 patients (group A) and 67 patients (group B) into two late phase II studies. All patients had no previous chemotherapy and had measurable disease. Gemcitabine was administered at a starting dose of 1,000 mg/m2/wk for 3 weeks followed by a week of rest. The dose was escalated to 1,250 mg/m2 if severe toxicity was not seen in the previous course. Nineteen of 73 patients (26%) had a partial response (95% confidence interval, 16.5% to 37.6%) in group A. Of 67 patients, 14 (20.9%) showed a partial response (95% confidence interval, 11.9% to 32.6%) in group B. Grade 3 or greater anemia and leukopenia occurred, respectively, in 15 (20.5%) and seven (9.6%) patients in group A and in nine (13.4%) and seven (10.4%) patients in group B. Grade 3 thrombocytopenia was observed in one patient (1.4%). Other toxicities including hepatic toxicity, fatigue, nausea/vomiting, and fever were mild and transient. Pulmonary toxicity was observed in five patients, two of whom died of respiratory insufficiency. The median durations of response were 19.6 weeks in group A and 20 weeks in group B, and median survival times were 44 and 39 weeks, respectively. In conclusion, gemcitabine is an active agent against non-small cell lung cancer with very mild toxicities. These results suggest that gemcitabine has potential utility on an outpatient basis. Further trials in combination with other active agents are warranted.
 ...
PMID:Phase II studies of gemcitabine for non-small cell lung cancer in Japan. 919 79

Gemcitabine is a novel nucleoside analog with unique activity against a wide range of solid tumors. We initiated a multicenter phase II study in patients with non-small cell lung cancer (NSCLC) to evaluate the efficacy and safety of gemcitabine. Eligible patients had stage III and IV, previously untreated with chemotherapy, age range from 18 to 80 years, and ECOG performance status 0 2. Gemcitabine was administered at 1000 mg/m2 as a continuous i.v. infusion once a week for a consecutive 3 week period, followed by 1 week of rest. Of the 69 patients enrolled, 67 patients were eligible for efficacy evaluation. The overall response rate was 20.9% with a 95% confidence interval of 11.9-32.6%. The median survival time was 9.0 months and the 12 month survival rate was 31.3%. Grade 3 or 4 toxicities included neutropenia in 22.7%, anemia in 13.4%, leukopenia in 10.4%, anorexia in 10.4%, malaise in 7.5% and nausea/vomiting in 6.0%. Serious toxicities were septic shock and interstitial pneumonia (one patient each). Gemcitabine, administered weekly for three consecutive weeks followed by 1 week of rest, is an active agent for NSCLC. Gemcitabine is currently being evaluated in combination with cisplatin and other agents.
 ...
PMID:Activity of gemcitabine in the treatment of patients with non-small cell lung cancer: a multicenter phase II study. 930 May 71

Gemcitabine (2',2'-difluorodeoxycytidine) is a novel nucleoside analogue. As part of a series of studies to determine the maximum tolerated dose (MTD) of gemcitabine and the most appropriate schedule, a two-centre phase I study of gemcitabine was undertaken in patients with advanced refractory solid tumours using a once every 2 weeks schedule. Fifty-two patients were entered into the study at 14 different dose levels (40-5700 mg m-2). Weekly evaluations for toxicity were performed and the MTD for this once every 2 weeks schedule was 5700 mg m-2. The dose-limiting toxicity was myelosuppression, with neutropenia being most significant. Other toxicities were nausea, vomiting, fever and asthenia. One minor response was seen in a heavily pretreated breast cancer patient treated at 1200 mg m-2. Preclinical studies suggest that the efficacy of gemcitabine is more schedule than dose related, and it is concluded that this is not the most appropriate dosing schedule for gemcitabine. However, this study demonstrates the safety profile of gemcitabine, as doses over fourfold greater than that recommended for the weekly schedule of 1000 mg m-2 could be tolerated.
 ...
PMID:Phase I study of gemcitabine using a once every 2 weeks schedule. 940 Sep 47

Gemcitabine has shown single-agent activity in metastatic breast cancer. Epirubicin is also widely used for the adjuvant and treatment of metastatic breast cancer. The toxicity profiles and modes of action are different which provides a good rationale for studying both drugs in combination. In a phase I study gemcitabine at a fixed dose of 1000 mg/m2 on days 1, 8, 15 of a 28 day cycle was combined with escalated weekly doses of epirubicin starting with an initial dose of 10 mg/m2. Patients had stage IV metastatic disease without previous chemotherapy except as adjuvant treatment. Nineteen patients were included in the study which defined the maximum tolerated dose (MTD) of epirubicin at 20 mg/m2. Myelosuppression was the dose limiting toxicity with leucopenia WHO grade 3 and 4 in 40.0% and 20.0%, neutropenia WHO grade 3 and 4 without neutropenic fever in 20.0% and 40.0% and thrombocytopenia WHO grade 4 in 20.0%. At the epirubicin 15 mg/m2 dose level, leucopenia (11.1% WHO grade 3) and neutropenia (12.5 and 37.5% WHO grade 3 and 4) were reported. Symptomatic toxicity was generally mild: nausea/vomiting in about 20% of patients (WHO grade 3 or 4) on both 15 and 20 mg/m2 epirubicin dose levels. Alopecia WHO grade 3 and 4 was seen in 2 patients at MTD. Four of 19 evaluable patients had a partial response. We conclude that the combination of gemcitabine and epirubicin is well tolerated and has promising activity. A phase II study is underway with gemcitabine 1000 mg/m2 and epirubicin 15 mg/m2 on days 1, 8 and 15 of a 28 day cycle.
 ...
PMID:Gemcitabine plus dose-escalated epirubicin in advanced breast cancer: results of a phase I study. 984 77

To determine the activity and toxicity of gemcitabine in non-small cell lung cancer, three phase II studies of single agent gemcitabine have been conducted between 1990 and 1994. In an early phase II study, gemcitabine was administered of 800 mg/m2 on day 1, 8, 15 every four weeks (step I), and 1,000 mg/m2 (step II). Response was observed in 3 of 13 patients with previously untreated non-small cell lung cancer, although there was no responders in the previously treated patients. Late phase II studies were performed at 20 (group A) and 24 (group B) Japanese institutions to confirm the efficacy and safety of gemcitabine administered alone in patients with non-small cell lung cancer. Seventy-three patients (group A) and 67 patients (group B) were entered into these studies. All patients had no previous chemotherapy and had measurable disease. Gemcitabine was administered at a starting dose of 1,000 mg/m2/wk for 3 weeks followed by a week of rest. The dose was escalated to 1,250 mg/m2 if severe toxicity was not seen in the previous course. Nineteen of 73 patients (26%) had a partial response in group A. Of 67 patients, 14 (20.9%) showed a partial response in group B. Grade 3 or greater toxicities included anemia (20.5%) and leukopenia (9.6%) in group A, and in 13.4% and seven 10.4% in group B, respectively. And grade 3 thrombocytopenia was observed in 1.4%. Other toxicities including hepatic toxicity, fatigue, nausea/vomiting, and fever were mild and transient. Pulmonary toxicity was observed in five patients, two of whom died of ARDS. The median durations of response were 19.6 weeks in group A and 20 weeks in group B, and median survival times were 44 and 39 weeks, respectively. In conclusion, gemcitabine is an active agent against non-small cell lung cancer with very mild toxicities. These results suggest that gemcitabine has potential utility in advanced non-small cell lung cancer on an outpatient basis. Further trials in combination with other active agents are warranted.
 ...
PMID:[Phase II studies of gemcitabine for non-small cell lung cancer in Japan]. 1039 14

The combination Phase I study of gemcitabine hydrochloride with cisplatin was conducted in the patients with non-small cell lung cancer (NSCLC) at 5 investigation sites. Gemcitabine was administrated on day 1, 8 and 15 and cisplatin on day 1 of each 28-day cycle. The dosage of cisplatin was fixed to 80 mg/m2 and the dosage of Gemcitabine was gradually escalated in 3 dosing level from 600, 800 to 1,000 mg/m2. The maximum tolerated dose (MTD) and the recommended dose was determined with Continual Reassessment Method. For each dose level, 6 cases, 3 cases and 6 cases were registered respectively and all 15 cases were evaluable. In the dose level 3 with 1,000 mg/m2 of gemcitabine and 80 mg/m2 of cisplatin, grade 4 neutropenia was observed as DLT in 3 out of 6 cases, thus dose level 3 was considered as MTD and the recommended dose. Major adverse events were leukopenia, neutropenia, nausea/vomiting and anorexia. The incidence of such adverse events seemed to be dose-dependent and especially the grade of neutropenia seemed to be more serious as the dose increased. Also, the grade of liver function tests abnormal seemed to be more serious as the dose increased but the incidence as well as the grade did not have tendency of dose-dependent in another events including renal function tests abnormal. On the other hand, as to the efficacy PR was observed in 4 out of 15 cases. Based upon the results, it is necessary to discuss further the efficacy in the recommended dose in the combination therapy of gemcitabine and cisplatin.
 ...
PMID:[Phase I study of gemcitabine hydrochloride (LY 188011) combination therapy with cisplatin in the patients with non-small cell lung cancer]. 1039 16

We report on the case of a 42-year-old man suffering from an irresectable adenocarcinoma of the liver. The patient was treated with 5-fluorouracil for 6 months when the disease progressed and second line therapy with gemcitabine was started. After 4 months diastolic blood pressure increased and edema of the legs as well as vomiting occurred. Laboratory tests revealed anemia and thrombopenia accompanied by an elevation of plasma D-dimer, lactatdehydrogenase, creatinine, and urea levels in the serum. In addition, a pronounced proteinuria as well as renal hematuria were detected and subsequently a hemolytic uremic syndrome was diagnosed. After treatment with high-dose glucocorticoids, anticoagulants and transfusions of packed RBC the course of disease improved. Since Gemcitabine is now widely used for treatment of solid organ cancer (e.g. pancreatic adenocarcinoma, biliary tract cancer, lung cancer etc.), it is necessary to be aware of Gemcitabine-induced hemolytic uremic syndrome as a rare but potentially fatal side effect.
 ...
PMID:[A 42-year-old patient with the hemolytic-uremic syndrome under gemcitabine therapy for an adenocarcinoma of the liver. The hemolytic-uremic syndrome and gemcitabine]. 1096 57


1 2 3 Next >>