Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 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)
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PMID:Weekly gemcitabine in advanced or metastatic solid tumors. A clinical phase I study. 786 Feb 27

The experience with single-agent gemcitabine in advanced or metastatic breast cancer is reviewed. In all studies, gemcitabine was administered as a 30 min intravenous infusion in cycles once a week for 3 weeks followed by 1 week of rest. In the first European study (gemcitabine 800 mg/m2/week), of 40 evaluable patients, 14 were chemo-naive, 7 had received adjuvant chemotherapy, and 19 had received chemotherapy for metastatic disease. There were 3 complete responders and 7 partial responders (all independently validated by an external Oncology Review Board) for an overall response rate of 25.0% (95% CI: 12.7%-41.2%). The median time to declaration of response was 1.9 months and the median duration of survival for all 40 efficacy-evaluable patients was 11.5 months. Haematological and non-haematological toxicities were particularly mild. WHO grade 3 and 4 toxicities included leukopenia (6.8% and 2.3% of patients), neutropenia (23.3% and 7.0%), AST (6.8% and 2.3%), ALT (18.2% and 0%), infection (0% and 2.3%), nausea and vomiting (25.0% and 2.3%), alopecia (2.3% and 0%). There was no grade 3 or 4 creatinine, proteinuria or haematuria. In the smaller US study (18 evaluable patients, all but one having received prior chemotherapy for stage IV disease) there were no responders. However, the mean dose delivered was very low (577 mg/m2/injection). In an ongoing European trial, with a starting dose of 1000 mg/m2, a number of partial responders have been seen in soft tissue, lung and liver. Gemcitabine's modest toxicity profile and single-agent activity make it an attractive candidate for trial in combination therapy in advanced breast cancer where treatment is currently given to palliate symptoms and improve quality of life.
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PMID:Gemcitabine in advanced breast cancer. 871 26

Gemcitabine, a novel anticancer agent, has been shown to be active in several human solid tumours, including non-small cell lung cancer and pancreatic cancer. In addition, gemcitabine has been noted to have a particularly mild safety profile for such an active agent and is lacking some of the classical toxicities of oncolytics, i.e. alopecia, severe nausea and vomiting, and mucositis. Therefore, the safety data from 790 patients in 18 completed clinical studies were integrated to study its toxicity profile in more detail. In all of these studies gemcitabine was administered as a 30-minute intravenous infusion every week for three weeks followed by a week of rest (one cycle). This integrated database confirmed that gemcitabine is well tolerated. Its haematological toxicity was mild and short lasting. The low incidence of infection was correspondingly low. Transaminase elevations occurred frequently, but they were usually mild and rarely dose-limiting. Mild proteinuria and haematuria were seen but were rarely clinically significant. There was no evidence of cumulative hepatic or renal toxicity. Nausea and vomiting were mild, rarely dose-limiting and generally well controlled with standard antiemetics. Flu-like symptoms were experienced in a proportion of patients but were short-lasting. Where oedema or peripheral oedema were experienced, there was no evidence of any association with cardiac, hepatic or renal failure. Hair loss was rare. The integrated database was also analysed according to starting dose (800, 1000 or 1250 mg/m2) in a subset of 665 chemonaive patients to see whether an increased dose resulted in increased toxicity. In general, only small, clinically insignificant differences in toxicity were seen between the three dose groups. Although segmented neutrophil count appeared to increase as starting dose increased (grade 3 or 4, 19.4%, 23.2%, 28.3% respectively), this was not associated with an increased incidence of infection. In some cases, toxicity decreased with increasing dose but this may have been because of imbalances between the patient groups. These findings indicate that not only is gemcitabine well tolerated, but it also has a broad therapeutic index and the use of higher doses may be possible.
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PMID:Gemcitabine: safety profile unaffected by starting dose. 900 25

Gemcitabine is a novel fluorine-substituted cytarabine (Ara-C) analogue with activity against a range of solid tumours. Besides dose-limiting haematological toxicity, renal side-effects were observed from phase I and II studies concerning elevations of serum creatinine, proteinuria and erythrocyturia. The aim of this study was to investigate the effect of gemcitabine on renal function in 11 untreated patients with non-small cell lung cancer (NSCLC). Gemcitabine was given as weekly infusions of 1250 mg/m2 for 3 weeks, followed by 1 week rest. This comprised one cycle (maximum of six cycles). The glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured simultaneously with a constant infusion of 125I-iothalamate and 131I-hippuran, respectively. Tubular damage was monitored by excretion of tubular enzymes (lactic dehydrogenase (LDH), alkaline phosphatase (ALP), gamma-glutamyltransferase (GT) and beta 2-microglobulin); glomerular damage was monitored by excretion of albumin in the urine. In 9 patients, the effect of the first infusion was evaluated. After the first infusion of gemcitabine, no change was observed in renal function. After two, three, and six cycles of treatment, no significant changes in GFR and ERPF were noticed in 9 evaluable patients. However, in 3 patients, a decrease in GFR of > 10% was observed after multiple cycles. In one of them this was accompanied with albuminuria (360 mg/24 h) and erythrocyturia. There were no significant changes in urinary excretion of tubular enzymes or albumin. In conclusion, we did not observe acute renal toxicity with gemcitabine. No significant cumulative effects of gemcitabine on renal function could be detected, although 3 patients, treated with multiple cycles of gemcitabine, showed a moderate decrease in renal function. Glomerular damage might play a role in the development of renal function loss.
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PMID:Effects of gemcitabine on renal function in patients with non-small cell lung cancer. 962 59

Gemcitabine is a novel nucleoside analog with demonstrated efficacy across a range of solid tumors. This paper reviews the single-agent safety profiles of 979 patients in 22 completed clinical studies using a day 1, 8, 15 q 28 day, 800-1250 mg/m2 dose schedule. Hematological toxicity was mild with WHO grade 3 and 4 toxicities recorded for hemoglobin (6.8 and 1.3% of patients), leukocytes (8.6 and 0.7%), neutrophils (19.3 and 6.0%) and platelets (4.1 and 1.1%). Myelosuppression was short lived and rarely of clinical significance. Mucositis and alopecia were rare, and nausea and vomiting mild. Transient rises in transaminases, mild proteinuria and hematuria were common, but rarely clinically significant. Renal failure of uncertain etiology was reported in seven instances. Some patients (18.9%) experienced transient flu-like symptoms and mild fever was reported in 37.3% of flu patients. Peripheral edema was reported in 20.3% of patients in the absence of cardiac, hepatic or renal failure. Thus, gemcitabine is well tolerated and has a mild toxicity profile. Of nearly 11,000 protocol-defined injections, 94% were administered and only 14% were reduced. Grade 3 or 4 non-laboratory toxicities with a frequency of more than 1% were only seen for infection (1.2%), nausea and vomiting (18.4%), and pulmonary toxicity (1.4%).
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PMID:Gemcitabine--a safety review. 962 29

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.
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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